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Sample records for aged rhesus monkeys

  1. Longitudinal Analysis of Early Stage Sarcopenia in Aging Rhesus Monkeys

    OpenAIRE

    McKiernan, Susan H; Colman, Ricki; Lopez, Marisol; Beasley, T.Mark; Weindruch, Richard; Aiken, Judd M.

    2008-01-01

    We present a longitudinal study using the rhesus monkey to determine biochemical and histological changes in vastus lateralis (VL) muscle fibers and whether these changes correlate with muscle mass loss. Dual energy x-ray absorptiometry (DXA) was used to determine body weight, body fat and to estimate upper leg muscle mass in twelve adult male rhesus monkeys over 12 years. Muscle mass (MM) was evaluated at years six, nine and twelve of the study. Concurrently, VL muscle biopsy samples were co...

  2. Lens diameter and thickness as a function of age and pharmacologically stimulated accommodation in rhesus monkeys

    OpenAIRE

    Wendt, Mark; Croft, Mary Ann; McDonald, Jared; Kaufman, Paul L; Glasser, Adrian

    2008-01-01

    Uncertainty exists regarding accommodative and age changes in lens diameter and thickness in humans and monkeys. In this study, unaccommodated and accommodated refraction, lens diameter, and lens thickness were measured in rhesus monkeys across a range of ages. Iridectomized eyes were studied in 33 anesthetized monkeys aged 4–23 years. Refraction was measured using a Hartinger coincidence refractometer and lens thickness was measured with A-scan ultrasound. Lens diameters were measured with i...

  3. Auditory Function in Rhesus Monkeys: Effects of Aging and Caloric Restriction in the Wisconsin Monkeys Five Years Later

    OpenAIRE

    Fowler, Cynthia G.; Chiasson, Kirstin Beach; Leslie, Tami Hanson; Thomas, Denise; Beasley, T. Mark; Kemnitz, Joseph W; Weindruch, Richard

    2010-01-01

    Caloric restriction (CR) slows aging in many species and protects some animals from age-related hearing loss (ARHL), but the effect on humans is not yet known. Because rhesus monkeys are long-lived primates that are phylogenically closer to humans than other research animals are, they provide a better model for studying the effects of CR in aging and ARHL. Subjects were from the pool of 55 rhesus monkeys aged 15–28 years who had been in the Wisconsin study on CR and aging for 8–13.5 years. Di...

  4. Caloric restriction delays aging-induced cellular phenotypes in rhesus monkey skeletal muscle

    OpenAIRE

    McKiernan, Susan H.; Colman, Ricki J; Lopez, Marisol; Beasley, T. Mark; Aiken, Judd M.; Anderson, Rozalyn M; Weindruch, Richard

    2010-01-01

    Sarcopenia is the age-related loss of skeletal muscle mass and function and is characterized by a reduction in muscle mass and fiber cross-sectional area, alterations in muscle fiber type and mitochondrial functional changes. In rhesus monkeys, calorie restriction (CR) without malnutrition improves survival and delays the onset of age-associated diseases and disorders including sarcopenia. We present a longitudinal study on the impact of CR on early stage sarcopenia in the upper leg of monkey...

  5. Patterns of cognitive decline in aged rhesus monkeys.

    Science.gov (United States)

    Herndon, J G; Moss, M B; Rosene, D L; Killiany, R J

    1997-08-01

    Although cognitive decline has been well established as a consequence of aging in non-human primate models, the prevalence or frequency of impairment for specific age ranges has not been described. The first aim of this study was to estimate prevalence of cognitive impairment on each of the six tests of cognitive performance by comparing the performance of early-aged (19-23 years old), advanced-aged (24-28 years old), and oldest-aged (29+ years old) monkeys to that of young adults (acquisition of the delayed non-matching-to-sample task (DNMS); (2) performance of the DNMS with a delay of 120 sec; (3) the spatial condition of the delayed recognition span test (DRST); (4) the color condition of the DRST; (5) spatial reversal learning; and (6) object reversal learning. Early-aged monkeys displayed prevalence rates of impairment significantly greater than zero on all tasks except the DRST-color. The highest prevalence of impairment was observed in this age group in a task measuring spatial memory (DRST). Significant trends toward progressively higher impairment rates in advanced-aged and oldest-aged monkeys were observed for DNMS-acquisition, DRST-color and spatial reversal learning tasks. A linear transformation of standardized scores on the six cognitive tests was derived by means of principal components analysis (PCA). The first PCA (PCA1) included data from 30 monkeys with available data on all six measures, and yielded a composite measure which declined linearly with increasing age (r = -0.74). A second PCA (PCA2) was performed on data from 53 monkeys for which three test scores (DNMS-acquisition, DNMS-120s delay, and DRST-spatial condition) were available. The composite score derived from this analysis was highly correlated (r = 0.93) with the composite score from PCA1, suggesting that a score based on only three tests may provide an adequate classification of global cognitive ability. PMID:9331471

  6. Relationships among cognitive function, fine motor speed and age in the rhesus monkey

    OpenAIRE

    Lacreuse, Agnès; Espinosa, Paola M.; Herndon, James G.

    2006-01-01

    Declines in fine motor skills and cognitive function are well known features of human aging. Yet, the relationship between age-related impairments in motor and cognitive function remains unclear. Rhesus monkeys, like humans, show marked decline in cognitive and fine motor function with age and are excellent models to investigate potential interactions between age-related declines in cognitive and motor functioning. We investigated the relationships among cognition, motor function and age in 3...

  7. Capillary changes in hippocampal CA1 and CA3 areas of the aging rhesus monkey

    OpenAIRE

    Keuker, JIH; Luiten, PGM; Fuchs, E.

    2000-01-01

    The rhesus monkey is considered a useful animal model for studying human aging, because non-human primates show many of the neurobiological alterations that have been reported in aging humans. Cognitive impairment that accompanies normal aging may, at least partially, originate from capillary changes in the hippocampus, known to be involved in learning and memory. Age-related effects on the cerebral capillaries in the nonhuman primate hippocampus have not yet been studied. Therefore, we inves...

  8. A REVIEW OF THE STRUCTURAL ALTERATIONS IN THE CEREBRAL HEMISPHERES OF THE AGING RHESUS MONKEY

    OpenAIRE

    Peters, Alan; Kemper, Thomas

    2011-01-01

    Like humans, rhesus monkeys show cognitive decline and this review considers what structural age-related changes underlie this decline. Some structural measures do not alter significantly with age. These include brain weight, overall cortical thickness; numbers of cortical neurons; and numbers of astrocytes and microglial cells. Other structural measures change with age, but the change does not correlate with cognitive decline. These changes include nerve fiber loss from some fiber tracts, de...

  9. EFFECTS OF NORMAL AGING ON PREFRONTAL AREA 46 IN THE RHESUS MONKEY

    OpenAIRE

    Luebke, Jennifer; Barbas, Helen; Peters, Alan

    2009-01-01

    This review is concerned with the effects of normal aging on the structure and function of prefrontal area 46 in the rhesus monkey (Macaca mulatta). Area 46 has complex connections with somatosensory, visual, visuomotor, motor and limbic systems and a key role in cognition, which frequently declines with age. An important question is what alterations might account for this decline. We are nowhere near having a complete answer, but as will be shown in this review, it is now evident that there ...

  10. Impaired Spatial Working Memory Learning and Performance in Normal Aged Rhesus Monkeys

    OpenAIRE

    Zeamer, Alyson; Clark, Kathryn; Bouquio, Courtney; Decamp, Emmanuel; Jay S Schneider

    2012-01-01

    Aged non-human primates may have deficits in a variety of cognitive functions. However, it is possible that at least some age-related performance deficits relate to a deficit in initial task learning. To assess this, aged rhesus monkeys were trained to perform a Self-Ordered Spatial Search task (SOSS) using the same training and testing parameters used previously with normal young animals. Aged animals failed to reach criterion at the easiest task level. In an attempt to improve learning, a g...

  11. Attention, executive functioning and memory in normal aged rhesus monkeys

    OpenAIRE

    Zeamer, Alyson; Decamp, Emmanuel; Clark, Kathryn; Schneider, J.S.

    2010-01-01

    Understanding how cognition declines in normal aging is vital in order to distinguish between normal cognitive decline due to aging and cognitive decline due to an age-related pathological process such as Parkinson’s disease (PD). Several cognitive domains including memory, executive functioning and attention are all adversely affected with age in humans, as well as by PD, yet less is known about how these processes are affected by aging in non-human primates. Thus, in order to characterize b...

  12. Preservation of hippocampal neuron numbers in aged rhesus monkeys

    NARCIS (Netherlands)

    Keuker, J.I.H.; Luiten, P.G.M.; Fuchs, E.

    2003-01-01

    To investigate whether or not aging of nonhuman primates is accompanied by a region-specific neuron loss in the hippocampal formation, we used the optical fractionator technique to obtain stereological estimates of unilateral neuron numbers of the hippocampi of eight young (0-4 years) and five aged

  13. Age-Specific Gene Expression Profiles of Rhesus Monkey Ovaries Detected by Microarray Analysis.

    Science.gov (United States)

    Wei, Hengxi; Liu, Xiangjie; Yuan, Jihong; Li, Li; Zhang, Dongdong; Guo, Xinzheng; Liu, Lin; Zhang, Shouquan

    2015-01-01

    The biological function of human ovaries declines with age. To identify the potential molecular changes in ovarian aging, we performed genome-wide gene expression analysis by microarray of ovaries from young, middle-aged, and old rhesus monkeys. Microarray data was validated by quantitative real-time PCR. Results showed that a total of 503 (60 upregulated, 443 downregulated) and 84 (downregulated) genes were differentially expressed in old ovaries compared to young and middle-aged groups, respectively. No difference in gene expression was found between middle-aged and young groups. Differentially expressed genes were mainly enriched in cell and organelle, cellular and physiological process, binding, and catalytic activity. These genes were primarily associated with KEGG pathways of cell cycle, DNA replication and repair, oocyte meiosis and maturation, MAPK, TGF-beta, and p53 signaling pathway. Genes upregulated were involved in aging, defense response, oxidation reduction, and negative regulation of cellular process; genes downregulated have functions in reproduction, cell cycle, DNA and RNA process, macromolecular complex assembly, and positive regulation of macromolecule metabolic process. These findings show that monkey ovary undergoes substantial change in global transcription with age. Gene expression profiles are useful in understanding the mechanisms underlying ovarian aging and age-associated infertility in primates. PMID:26421297

  14. Radioimmunoassay for rhesus monkey gonadotropins

    International Nuclear Information System (INIS)

    Heterologous double-antibody radioimmunoassay methods are described for the measurement of circulating levels of rhesus monkey (Macaca mulatta) FSH and LH; the latter assay is also applicable to rhesus chorionic gonadotropin (CG) estimations. The FSH assay utilizes purified rat FSH for trace, either of two anti-human FSH antisera and a semipurified rhesus pituitary standard. The LH assay utilizes purified ovine LH for trace, an anti-human CG antiserum and the same rhesus pituitary standard. The use of these systems obviates the necessity of purifying rhesus gonadotropins which are required for the development of homologous radioimmunoassay systems. (U.S.)

  15. Brain volumetric and microstructural correlates of executive and motor performance in aged rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Aadhavi eSridharan

    2012-11-01

    Full Text Available The aged rhesus macaque exhibits brain atrophy and behavioral deficits similar to normal aging in humans. Here we studied the association between cognitive and motor performance and anatomic and microstructural brain integrity measured with 3T magnetic resonance imaging in aged monkeys. About half of these animals were maintained on moderate calorie restriction, the only intervention shown to delay the aging process in lower animals. T1-weighted anatomic and diffusion tensor images were used to obtain gray matter volume, and fractional anisotropy and mean diffusivity, respectively. We tested the extent to which brain health indexed by gray matter volume, fractional anisotropy, and mean diffusivity were related to executive and motor function, and determined the effect of the dietary intervention on this relationship. We hypothesized that fewer errors on the executive function test and faster motor times would be correlated with higher volume, higher fractional anisotropy, and lower mean diffusivity in frontal areas that mediate executive function, and in motor, premotor, subcortical, and cerebellar areas underlying goal-directed motor behaviors. Higher error percentage on a cognitive conceptual shift task was significantly associated with lower gray matter volume in frontal and parietal cortices, and lower fractional anisotropy in major association fiber bundles. Similarly, slower performance time on the motor task was significantly correlated with lower volumetric measures in cortical, subcortical, and cerebellar areas and decreased fractional anisotropy in several major association fiber bundles. Notably, performance during the acquisition phase of the hardest level of the motor task was significantly associated with anterior mesial temporal lobe volume. Finally, these brain-behavior correlations for the motor task were attenuated in calorie restricted animals compared to controls, indicating a potential protective effect of the dietary

  16. Estrogen Restores Multisynaptic Boutons in the Dorsolateral Prefrontal Cortex while Promoting Working Memory in Aged Rhesus Monkeys.

    Science.gov (United States)

    Hara, Yuko; Yuk, Frank; Puri, Rishi; Janssen, William G M; Rapp, Peter R; Morrison, John H

    2016-01-20

    Humans and nonhuman primates are vulnerable to age- and menopause- related decline in working memory, a cognitive function reliant on area 46 of the dorsolateral prefrontal cortex (dlPFC). We showed previously that presynaptic mitochondrial number and morphology in monkey dlPFC neurons correlate with working memory performance. The current study tested the hypothesis that the types of synaptic connections these boutons form are altered with aging and menopause in rhesus monkeys and that these metrics may be coupled with mitochondrial measures and working memory. Using serial section electron microscopy, we examined the frequencies and characteristics of nonsynaptic, single-synaptic, and multisynaptic boutons (MSBs) in the dlPFC. In contrast to our previous observations in the monkey hippocampal dentate gyrus, where MSBs comprised ∼40% of boutons, the vast majority of dlPFC boutons were single-synaptic, whereas MSBs constituted a mere 10%. The frequency of MSBs was not altered by normal aging, but decreased by over 50% with surgical menopause induced by ovariectomy in aged monkeys. Cyclic estradiol treatment in aged ovariectomized animals restored MSB frequencies to levels comparable to young and aged premenopausal monkeys. Notably, the frequency of MSBs positively correlated with working memory scores, as measured by the average accuracy on the delayed response (DR) test. Furthermore, MSB incidence positively correlated with the number of healthy straight mitochondria in dlPFC boutons and inversely correlated with the number of pathological donut-shaped mitochondria. Together, our data suggest that MSBs are coupled to cognitive function and mitochondrial health and are sensitive to estrogen. Significance statement: Many aged menopausal individuals experience deficits in working memory, an executive function reliant on recurrent firing of prefrontal cortex (PFC) neurons. However, little is known about the organization of presynaptic inputs to these neurons and how

  17. Cellular adaptation contributes to calorie restriction-induced preservation of skeletal muscle in aged rhesus monkeys

    OpenAIRE

    McKiernan, Susan H; Colman, Ricki J; Aiken, Erik; Evans, Trent D.; Beasley, T.Mark; Aiken, Judd M.; Weindruch, Richard; Anderson, Rozalyn M.

    2011-01-01

    We have previously shown that a 30% reduced calorie intake diet delayed the onset of muscle mass loss in adult monkeys between ~16 and ~22 years of age and prevented multiple cellular phenotypes of aging. In the present study we show the impact of long term (~17 years) calorie restriction (CR) on muscle aging in very old monkeys (27–33yrs) compared to age-matched Control monkeys fed ad libitum, and describe these data in the context of the whole longitudinal study. Muscle mass was preserved i...

  18. Epidurography with metrizamide in Rhesus monkeys

    International Nuclear Information System (INIS)

    Epidurography with metrizamide was performed on 9 Rhesus monkeys; physiologic saline was substituted for metrizamide in 3 control monkeys. Metrizamide successfully outlined the epidural space without causing any adverse clinical effects or direct tissue injury. (Auth.)

  19. Cellular adaptation contributes to calorie restriction-induced preservation of skeletal muscle in aged rhesus monkeys.

    Science.gov (United States)

    McKiernan, Susan H; Colman, Ricki J; Aiken, Erik; Evans, Trent D; Beasley, T Mark; Aiken, Judd M; Weindruch, Richard; Anderson, Rozalyn M

    2012-03-01

    We have previously shown that a 30% reduced calorie intake diet delayed the onset of muscle mass loss in adult monkeys between ~16 and ~22 years of age and prevented multiple cellular phenotypes of aging. In the present study we show the impact of long term (~17 years) calorie restriction (CR) on muscle aging in very old monkeys (27-33 yrs) compared to age-matched Control monkeys fed ad libitum, and describe these data in the context of the whole longitudinal study. Muscle mass was preserved in very old calorie restricted (CR) monkeys compared to age-matched Controls. Immunohistochemical analysis revealed an age-associated increase in the proportion of Type I fibers in the VL from Control animals that was prevented with CR. The cross sectional area (CSA) of Type II fibers was reduced in old CR animals compared to earlier time points (16-22 years of age); however, the total loss in CSA was only 15% in CR animals compared to 36% in old Controls at ~27 years of age. Atrophy was not detected in Type I fibers from either group. Notably, Type I fiber CSA was ~1.6 fold greater in VL from CR animals compared to Control animals at ~27 years of age. The frequency of VL muscle fibers with defects in mitochondrial electron transport system enzymes (ETS(ab)), the absence of cytochrome c oxidase and hyper-reactive succinate dehydrogenase, were identical between Control and CR. We describe changes in ETS(ab) fiber CSA and determined that CR fibers respond differently to the challenge of mitochondrial deficiency. Fiber counts of intact rectus femoris muscles revealed that muscle fiber density was preserved in old CR animals. We suggest that muscle fibers from CR animals are better poised to endure and adapt to changes in muscle mass than those of Control animals. PMID:22226624

  20. Metaphase yields from staphylococcal enterotoxin A stimulated peripheral blood lymphocytes of unirradiated and irradiated aged rhesus monkeys

    Science.gov (United States)

    Hill, F. S.; Cox, A. B.; Salmon, Y. L.; Cantu, A. O.; Lucas, J. N.

    1994-01-01

    The mitogen phytohemagglutinin (PHA) works well in both human and cynomolgus monkey (Macaca fascicularis) lymphocyte cultures to stimulate T cell proliferation. T cells from rhesus monkeys (Macaca mulatta) are less responsive than human cells, producing few metaphases when thousands are required, e.g. in biological dosimetry studies. We show that staphylococcal enterotoxin A (SEA), one of the most potent mitogens known, at a concentration of 0.5 microgram/ml stimulated peripheral lymphocytes to grow with a mitotic index (MI) averaging 0.13 metaphases/cell in old, irradiated rhesus macaques. This was significantly greater (p animals. Whole blood was cultured for 96, 120 and 144 h for five irradiated individuals and for two controls. All cells cultured with SEA produced a high MI with a peak response at 120 h whereas the same cultures showed low MI for each PHA stimulated culture.

  1. Physiology responses of Rhesus monkeys to vibration

    Science.gov (United States)

    Hajebrahimi, Zahra; Ebrahimi, Mohammad; Alidoust, Leila; Arabian Hosseinabadi, Maedeh

    Vibration is one of the important environmental factors in space vehicles that it can induce severe physiological responses in most of the body systems such as cardiovascular, respiratory, skeletal, endocrine, and etc. This investigation was to assess the effect of different vibration frequencies on heart rate variability (HRV), electrocardiograms (ECG) and respiratory rate in Rhesus monkeys. Methods: two groups of rhesus monkey (n=16 in each group) was selected as control and intervention groups. Monkeys were held in a sitting position within a specific fixture. The animals of this experiment were vibrated on a table which oscillated right and left with sinusoidal motion. Frequency and acceleration for intervention group were between the range of 1 to 2000 Hz and +0.5 to +3 G during 36 weeks (one per week for 15 min), respectively. All of the animals passed the clinical evaluation (echocardiography, sonography, radiography and blood analysis test) before vibration test and were considered healthy and these tests repeated during and at the end of experiments. Results and discussions: Our results showed that heart and respiratory rates increased significantly in response to increased frequency from 1 to 60 Hz (p controls. There were no significant differences in heart and respiratory rate from 60 t0 2000 Hz among studied groups. All monkeys passed vibration experiment successfully without any arrhythmic symptoms due to electrocardiography analysis. Conclusion: Our results indicate that vibration in low frequency can effect respiratory and cardiovascular function in rhesus monkey. Keywords: Vibration, rhesus monkey, heart rate, respiratory rate

  2. Automated evolutionary optimization of ion channel conductances and kinetics in models of young and aged rhesus monkey pyramidal neurons.

    Science.gov (United States)

    Rumbell, Timothy H; Draguljić, Danel; Yadav, Aniruddha; Hof, Patrick R; Luebke, Jennifer I; Weaver, Christina M

    2016-08-01

    Conductance-based compartment modeling requires tuning of many parameters to fit the neuron model to target electrophysiological data. Automated parameter optimization via evolutionary algorithms (EAs) is a common approach to accomplish this task, using error functions to quantify differences between model and target. We present a three-stage EA optimization protocol for tuning ion channel conductances and kinetics in a generic neuron model with minimal manual intervention. We use the technique of Latin hypercube sampling in a new way, to choose weights for error functions automatically so that each function influences the parameter search to a similar degree. This protocol requires no specialized physiological data collection and is applicable to commonly-collected current clamp data and either single- or multi-objective optimization. We applied the protocol to two representative pyramidal neurons from layer 3 of the prefrontal cortex of rhesus monkeys, in which action potential firing rates are significantly higher in aged compared to young animals. Using an idealized dendritic topology and models with either 4 or 8 ion channels (10 or 23 free parameters respectively), we produced populations of parameter combinations fitting the target datasets in less than 80 hours of optimization each. Passive parameter differences between young and aged models were consistent with our prior results using simpler models and hand tuning. We analyzed parameter values among fits to a single neuron to facilitate refinement of the underlying model, and across fits to multiple neurons to show how our protocol will lead to predictions of parameter differences with aging in these neurons. PMID:27106692

  3. Canine Distemper Outbreak in Rhesus Monkeys, China

    OpenAIRE

    Qiu, Wei; Zheng, Ying; Zhang, Shoufeng; Fan, Quanshui; Liu, Hua; Zhang, Fuqiang; Wang, Wei; Liao, Guoyang; Hu, Rongliang

    2011-01-01

    Since 2006, canine distemper outbreaks have occurred in rhesus monkeys at a breeding farm in Guangxi, People’s Republic of China. Approximately 10,000 animals were infected (25%–60% disease incidence); 5%–30% of infected animals died. The epidemic was controlled by vaccination. Amino acid sequence analysis of the virus indicated a unique strain.

  4. Spontaneous pericardial mesothelioma in a rhesus monkey.

    Science.gov (United States)

    Chandra, M; Mansfield, K G

    1999-06-01

    Spontaneous tumors in nonhuman primates are of great importance. A spontaneous pericardial mesothelioma was observed in an 18-year-old female rhesus monkey. Grossly, the visceral pericardium was multifocally irregular and thickened with tan discoloration and was soft in consistency. Histologically, the pericardium contained highly in-folded branching fronds lined by a single layer of cuboidal cells. Tumor invaded into approximately half of the thickness of the atrial and ventricular muscles. Tumor penetration was not observed into the atrial or ventricular cavity. Within the myocardium, neoplastic cells formed glandular structures which were lined by cuboidal to columnar cells. Neoplastic cells were weakly positive with PAS and strongly positive for colloid iron and alcian blue. Immunohistochemically, neoplastic cells were positive for both vimentin and cytokeratin and negative with CEA and Leu-M1, indicating mesothelial origin. To the best of the authors' knowledge, this is the first report of a spontaneous pericardial mesothelioma in a rhesus monkey. PMID:10475114

  5. Auditory looming perception in rhesus monkeys

    OpenAIRE

    Ghazanfar, Asif A.; Neuhoff, John G.; Logothetis, Nikos K.

    2002-01-01

    The detection of approaching objects can be crucial to the survival of an organism. The perception of looming has been studied extensively in the visual system, but remains largely unexplored in audition. Here we show a behavioral bias in rhesus monkeys orienting to “looming” sounds. As in humans, the bias occurred for harmonic tones (which can reliably indicate single sources), but not for broadband noise. These response biases to looming sounds are consistent with an evolved neural mechanis...

  6. Rhesus monkeys know when they remember

    OpenAIRE

    Hampton, Robert R.

    2001-01-01

    Humans are consciously aware of some memories and can make verbal reports about these memories. Other memories cannot be brought to consciousness, even though they influence behavior. This conspicuous difference in access to memories is central in taxonomies of human memory systems but has been difficult to document in animal studies, suggesting that some forms of memory may be unique to humans. Here I show that rhesus macaque monkeys can report the presence or absence...

  7. Volume effects in Rhesus monkey spinal cord

    International Nuclear Information System (INIS)

    An experiment was conducted to test for the existence of a volume effect in radiation myelopathy using Rhesus monkeys treated with clinically relevant field sizes and fractionation schedules. Five groups of Rhesus monkeys were irradiated using 2.2 Gy per fraction to their spinal cords. Three groups were irradiated with 8 cm fields to total doses of 70.4, 77, and 83.6 Gy. Two additional groups were irradiated to 70.4 Gy using 4 and 16 cm fields. The incidence of paresis expressed within 2 years following the completion of treatment was determined for each group. Maximum likelihood estimation was used to determine parameters of a logistic dose response function. The volume effect was modeled using the probability model in which the probability of producing a lesion in an irradiated volume is governed by the probability of the occurrence of independent events. This is a two parameter model requiring only the estimates of the parameters of the dose-response function for the reference volume, but not needing any additional parameters for describing the volume effect. The probability model using a logistic dose-response function fits the data well with the D50 = 75.8 Gy for the 8-cm field. No evidence was seen for a difference in sensitivities for different anatomical levels of the spinal cord. Most lesions were type 3, combined white matter parenchymal and vascular lesions. Latent periods did not differ significantly from those of type 3 lesions in humans. The spinal cord exhibits a volume effect that is well described by the probability model. Because the dose response function for radiation myelopathy is steep, the volume effect is modest. The Rhesus monkey remains the animal model most similar to humans in dose response, histopathology, and latency for radiation myelopathy. 22 refs., 3 figs., 1 tab

  8. Changes of spatial and temporal frequency tuning properties of neurons in the middle temporal area of aged rhesus monkeys.

    Science.gov (United States)

    Yuan, Nini; Liang, Zhen; Yang, Yun; Li, Guangxing; Zhou, Yifeng

    2014-08-01

    Aged humans exhibit severe deficits in visual motion perception and contrast sensitivity under various levels of spatial and temporal modulation. Previous studies indicated that many of these deficits are probably mediated by the neural degradation of the central visual system. To clarify the neuronal response mechanisms underlying the visual degradation during aging, we examined the spatial and temporal frequency tuning properties of neurons from anesthetised and paralysed aged monkeys at the middle temporal area (area MT), which is downstream of the primary visual cortex in the visual processing pathway and thought to be critical for motion perception. We found that the preferred spatial and temporal frequencies, spatial resolution and high temporal frequency cutoff of area MT neurons were reduced in aged monkeys, and were accompanied by the broadened tuning width of spatial frequency, elevated spontaneous activity, and decreased signal-to-noise ratio. These results showed that, for neurons in area MT, aging significantly changed both the spatial and temporal frequency response tuning properties. Such evidence provides new insight into the changes occurring at the electrophysiological level that may be related to the aging-related visual deficits, especially in processing spatial and temporal information. PMID:24888415

  9. Can Rhesus Monkey Learn Executive Attention?

    Directory of Open Access Journals (Sweden)

    Jessica Bramlett-Parker

    2016-06-01

    Full Text Available A growing body of data indicates that, compared to humans, rhesus monkeys perform poorly on tasks that assess executive attention, or voluntary control over selection for processing, particularly under circumstances in which attention is attracted elsewhere by competing stimulus control. In the human-cognition literature, there are hotly active debates about whether various competencies such as executive attention, working memory capacity, and fluid intelligence can be improved through training. In the current study, rhesus monkeys (Macaca mulatta completed an attention-training intervention including several inhibitory-control tasks (a Simon task, numerical Stroop task, global/local interference task, and a continuous performance task to determine whether generalized improvements would be observed on a version of the Attention Network Test (ANT of controlled attention, which was administered before and after the training intervention. Although the animals demonstrated inhibition of prepotent responses and improved in executive attention with practice, this improvement did not generalize to the ANT at levels consistently better than were observed for control animals. Although these findings fail to encourage the possibility that species differences in cognitive competencies can be ameliorated through training, they do advance our understanding of the competition between stimulus-control and cognitive-control in performance by nonhuman and human primates.

  10. Can Rhesus Monkey Learn Executive Attention?

    Science.gov (United States)

    Bramlett-Parker, Jessica; Washburn, David A

    2016-01-01

    A growing body of data indicates that, compared to humans, rhesus monkeys perform poorly on tasks that assess executive attention, or voluntary control over selection for processing, particularly under circumstances in which attention is attracted elsewhere by competing stimulus control. In the human-cognition literature, there are hotly active debates about whether various competencies such as executive attention, working memory capacity, and fluid intelligence can be improved through training. In the current study, rhesus monkeys (Macaca mulatta) completed an attention-training intervention including several inhibitory-control tasks (a Simon task, numerical Stroop task, global/local interference task, and a continuous performance task) to determine whether generalized improvements would be observed on a version of the Attention Network Test (ANT) of controlled attention, which was administered before and after the training intervention. Although the animals demonstrated inhibition of prepotent responses and improved in executive attention with practice, this improvement did not generalize to the ANT at levels consistently better than were observed for control animals. Although these findings fail to encourage the possibility that species differences in cognitive competencies can be ameliorated through training, they do advance our understanding of the competition between stimulus-control and cognitive-control in performance by nonhuman and human primates. PMID:27304969

  11. Anterior hypothalamic lesions and pubertal development in female rhesus monkeys.

    Science.gov (United States)

    van der Werff ten Bosch, J J; Dierschke, D J; Terasawa, E; Slob, A K

    1983-03-01

    Electrolytic lesions were made in the anterior hypothalamus of 8 prepubertal female rhesus monkeys, aged 1.1-1.7 years. Six unoperated females served as controls. No effects were found of the lesions upon age and body weight at menarche or at first ovulation, as estimated by blood levels of progesterone and laparoscopic observations. From these findings it appears that the neural control of puberty in the female rhesus may not be exerted through the anterior hypothalamus, in contrast with the rat and ferret. Further, an attempt was made to identify biometric correlates of hormonal changes during puberty. Firstly, the well known dip in growth rate, about 0.4 years before menarche, was observed. Secondly, there was a marked spurt in growth of the nipples starting at 0.2 years before menarche. The close temporal association between accelerated nipple growth and menarche suggests that both of these developmental characteristics result from changes in (presumably ovarian) steroid hormone secretion. PMID:6838715

  12. Impaired Preadipocyte Differentiation Into Adipocytes in Subcutaneous Abdominal Adipose of PCOS-Like Female Rhesus Monkeys

    OpenAIRE

    Keller, Erica; Chazenbalk, Gregorio D.; Aguilera, Paul; Madrigal, Vanessa; Grogan, Tristan; Elashoff, David; Daniel A Dumesic; David H Abbott

    2014-01-01

    Metabolic characteristics of polycystic ovary syndrome women and polycystic ovary syndrome-like, prenatally androgenized (PA) female monkeys worsen with age, with altered adipogenesis of sc abdominal adipose potentially contributing to age-related adverse effects on metabolism. This study examines whether adipocyte morphology and gene expression in sc abdominal adipose differ between late reproductive-aged PA female rhesus monkeys compared with age-matched controls (C). Subcutaneous abdominal...

  13. INTERCEPTIVE EFFECTS OF EPOSTANE IN RATS AND RHESUS MONKEYS

    Institute of Scientific and Technical Information of China (English)

    LINZhong-Ming; LIUChang-Guan; CHENHui-Qing; LIWei-Kang; XURui-Ying

    1989-01-01

    Interceptives arc defined as agents which interrupt pregnancy after implantation.Epostane, a potent 3β-hydroxysteruid dehydrogenase inhibitor, possessed interceptive activities in rats and rhesus monkeys. In rats, day 10 and day 11 of pregnancy were the

  14. Vestibuloocular reflex of rhesus monkeys after spaceflight

    Science.gov (United States)

    Cohen, Bernard; Kozlovskaia, Inessa; Raphan, Theodore; Solomon, David; Helwig, Denice; Cohen, Nathaniel; Sirota, Mikhail; Iakushin, Sergei

    1992-01-01

    The vestibuloocular reflex (VOR) of two rhesus monkeys was recorded before and after 14 days of spaceflight. The gain (eye velocity/head velocity) of the horizontal VOR, tested 15 and 18 h after landing, was approximately equal to preflight values. The dominant time constant of the animal tested 15 h after landing was equivalent to that before flight. During nystagmus induced by off-vertical axis rotation (OVAR), the latency, rising time constant, steady-state eye velocity, and phase of modulation in eye velocity and eye position with respect to head position were similar in both monkeys before and after flight. There were changes in the amplitude of modulation of horizontal eye velocity during steady-state OVAR and in the ability to discharge stored activity rapidly by tilting during postrotatory nystagmus (tilt dumping) after flight: OVAR modulations were larger, and tilt dumping was lost in the one animal tested on the day of landing and for several days thereafter. If the gain and time constant of the horizontal VOR exchange in microgravity, they must revert to normal soon after landing. The changes that were observed suggest that adaptation to microgravity had caused alterations in way that the central nervous system processes otolith input.

  15. Spaceflight and immune responses of rhesus monkeys

    Science.gov (United States)

    Sonnenfeld, Gerald; Morton, Darla S.; Swiggett, Jeanene P.; Hakenewerth, Anne M.; Fowler, Nina A.

    1995-01-01

    The effects of restraint on immunological parameters was determined in an 18 day ARRT (adult rhesus restraint test). The monkeys were restrained for 18 days in the experimental station for the orbiting primate (ESOP), the chair of choice for Space Shuttle experiments. Several immunological parameters were determined using peripheral blood, bone marrow, and lymph node specimens from the monkeys. The parameters included: response of bone marrow cells to GM-CSF (granulocyte-macrophage colony stimulating factor), leukocyte subset distribution, and production of IFN-a (interferon-alpha) and IFN-gamma (interferon-gamma). The only parameter changed after 18 days of restraint was the percentage of CD8+ T cells. No other immunological parameters showed changes due to restraint. Handling and changes in housing prior to the restraint period did apparently result in some restraint-independent immunological changes. Handling must be kept to a minimum and the animals allowed time to recover prior to flight. All experiments must be carefully controlled. Restraint does not appear to be a major issue regarding the effects of space flight on immune responses.

  16. Thermoregulatory responses of rhesus monkeys during spaceflight.

    Science.gov (United States)

    Sulzman, F M; Ferraro, J S; Fuller, C A; Moore-Ede, M C; Klimovitsky, V; Magedov, V; Alpatov, A M

    1992-03-01

    This study examines the activity, axillary temperature (T(ax)), and ankle skin temperature (Tsk) of two male Rhesus monkeys exposed to microgravity in space. The animals were flown on a Soviet biosatellite mission (COSMOS 1514). Measurements on the flight animals, as well as synchronous flight controls, were performed in the Soviet Union. Additional control studies were performed in the United States to examine the possible role of metabolic heat production in the T(ax) response observed during the spaceflight. All monkeys were exposed to a 24-h light-dark cycle (LD 16:8) throughout these studies. During weightlessness, T(ax) in both flight animals was lower than on earth. The largest difference (0.75 degree C) occurred during the night. There was a reduction in mean heart rate and Tsk during flight. This suggests a reduction in both heat loss and metabolic rate during spaceflight. Although the circadian rhythms in all variables were present during flight, some differences were noted. For example, the amplitude of the rhythms in Tsk and activity were attenuated. Furthermore, the T(ax) and activity rhythms did not have precise 24.0 hour periods and may have been externally desynchronized from the 24-h LD cycle. These data suggest a weakening of the coupling between the internal circadian pacemaker and the external LD synchronizer. PMID:1523235

  17. Brain tumors induced by radiation in rhesus monkeys

    International Nuclear Information System (INIS)

    Two out of four pubescent rhesus monkeys, which received 1,500 rads of supervoltage X-irradiation, showed malignant brain tumors afer the survival of 52 and 102 weeks each. Since the incidence of spontaneous developing brain tumors in monkeys cited in the literatures was quite low, the tumors in the present series may have been radiation induced. (author)

  18. Changes in the Frequency and In Vivo Vessel Forming Ability of Rhesus Monkey Circulating Endothelial Colony Forming Cells (ECFC) Across the Lifespan (Birth to Aged)

    OpenAIRE

    Shelley, W. Chris; Leapley, Alyssa C.; Huang, Lan; Critser, Paul J.; Mead, Laura E.; Zeng, Pingyu; Prater, Daniel; Ingram, David A.; Tarantal, Alice F; Yoder, Mervin C.

    2011-01-01

    We have identified a novel hierarchy of human endothelial colony forming cells (ECFC), which are functionally defined by their proliferative and clonogenic potential and in vivo vessel forming ability. Utilizing previously established clonogenic assays for defining different subpopulations of human ECFC, we now show that a hierarchy of ECFC, identical to the human system, can be isolated from the peripheral blood of rhesus monkeys (Macaca mulatta), and that the frequency of the circulating ce...

  19. Age-related alterations of plasma glutathione and oxidation of redox potentials in chimpanzee (Pan troglodytes) and rhesus monkey (Macaca mulatta)

    OpenAIRE

    Paredes, Jamespaul; Jones, Dean P.; Wilson, Mark E.; Herndon, James G.

    2014-01-01

    Chimpanzee (Pan troglodytes) and rhesus macaque (Macaca mulatta) and humans (Homo sapiens) share physiological and genetic characteristics, but have remarkably different life spans, with chimpanzees living 50–60 % and the rhesus living 35–40 % of maximum human survival. Since oxidative processes are associated with aging and longevity, we might expect to see species differences in age-related oxidative processes. Blood and extracellular fluid contain two major thiol redox nodes, glutathione (...

  20. Slit-lamp studies of the rhesus monkey eye: II. Changes in crystalline lens shape, thickness and position during accommodation and aging.

    Science.gov (United States)

    Koretz, J F; Bertasso, A M; Neider, M W; True-Gabelt, B A; Kaufman, P L

    1987-08-01

    Changes in crystalline lens shape and axial thickness, anterior chamber depth and anterior cornea-posterior lens distance during accommodation induced by corneal iontophoresis of carbachol or electrical stimulation of the Edinger-Westphal nucleus were studied in 25 living, surgically aniridic rhesus monkey eyes, aged 1-25 years. Intraocular distances and anterior and posterior lens surface curvatures were evaluated from slit-lamp Scheimpflug photographs; distances were also determined by A-scan ultrasonography. With increasing accommodation, both lens surfaces become more sharply curved, the lens thickens and the anterior chamber shallows, while the posterior lens surface remains fixed relative to the cornea. Within statistical limits, the respective curvature and distance changes are the same for a given dioptric accommodation induced by either stimulation technique. The respective intraocular distance-accommodation relationships are identical whether derived from photographic or ultrasonographic measurements. Temporal and contralateral reproducibility of all measurements is excellent. Each parameter-accommodation relationship is strikingly linear in all eyes, although above 20 D the slopes of the lens surface curvature-accommodation relationships may have decreased. The curvature change per D of accommodation averages approximately 20% more for the posterior than for the anterior lens surface. There is relatively little interindividual variation in the slope of each relationship despite the significant interindividual differences in age and accommodative amplitude, indicating that the relationships are independent of age. However, when extrapolated back to the non-accommodated resting state, the data indicate that the lens thickens, both its surfaces become more sharply curved, and the anterior chamber shallows with age in adult greater than 5 years, while opposite trends are seen in younger animals. PMID:3653294

  1. Pharmacokinetics of bisphenol A in neonatal and adult rhesus monkeys

    International Nuclear Information System (INIS)

    Bisphenol A (BPA) is a high-production volume industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of > 90% of Americans aged 6-60 is controversial because of the potential for endocrine disruption, particularly during perinatal development, as suggested by in vitro, experimental animal, and epidemiological studies. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal rhesus monkeys by oral (PND 5, 35, 70) and intravenous injection (PND 77) routes using d6-BPA to avoid sample contamination. The concentration-time profiles observed in adult monkeys following oral administration of 100 μg/kg bw were remarkably similar to those previously reported in human volunteers given a similar dose; moreover, minimal pharmacokinetic differences were observed between neonatal and adult monkeys for the receptor-active aglycone form of BPA. Circulating concentrations of BPA aglycone were quite low following oral administration (< 1% of total), which reflects the redundancy of active UDP-glucuronosyl transferase isoforms in both gut and liver. No age-related changes were seen in internal exposure metrics for aglycone BPA in monkeys, a result clearly different from developing rats where significant inverse age-related changes, based on immaturity of Phase II metabolism and renal excretion, were recently reported. These observations imply that any toxicological effect observed in rats from early postnatal exposures to BPA could over-predict those possible in primates of the same age, based on significantly higher internal exposures and overall immaturity at birth.

  2. Genomic diversity and evolution of papillomaviruses in rhesus monkeys.

    OpenAIRE

    Chan, S. Y.; Bernard, H U; Ratterree, M.; Birkebak, T A; Faras, A J; Ostrow, R S

    1997-01-01

    We are studying the diversity of and relationships among papillomaviruses (PVs) to understand the modes and timescales of PV evolution and in the hope of finding animal PVs that may serve as model systems for disease caused by human PVs (HPVs). Toward this goal, we have examined 326 genital samples from rhesus monkeys and long-tailed macaques with a PCR protocol optimized for detecting genital HPV types. In 28 of the rhesus monkey samples, we found amplicons derived from 12 different and nove...

  3. Facial expression recognition in rhesus monkeys, Macaca mulatta

    OpenAIRE

    Parr, Lisa A.; Heintz, Matthew

    2009-01-01

    The ability to recognize and accurately interpret facial expressions is critically important for nonhuman primates that rely on these nonverbal signals for social communication. Despite this, little is known about how nonhuman primates, particularly monkeys, discriminate between facial expressions. In the present study, seven rhesus monkeys were required to discriminate four categories of conspecific facial expressions using a matching-to-sample task. In experiment 1, the matching pair showed...

  4. A more consistent intraluminal rhesus monkey model of ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Bo Zhao; Fauzia Akbary; Shengli Li; Jing Lu; Feng Ling; Xunming Ji; Guowei Shang; Jian Chen; Xiaokun Geng; Xin Ye; Guoxun Xu; Ju Wang; Jiasheng Zheng; Hongjun Li

    2014-01-01

    Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiol-ogy in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group:middle cerebral artery occlusion at origin segment (M1) and middle cerebral artery occlusion at M2 segment. The blood lfow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique (1 mm × 10 cm) (undetachable), to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood lfow was restored. A revers-ible middle cerebral artery occlusion model was identiifed by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symp-toms of neurological deifcits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental ifndings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the ifeld of brain injury research.

  5. Comparative study of delayed brain damage in pubescent and adult rhesus monkeys from radiation within the therapeutic range

    International Nuclear Information System (INIS)

    The whole brains of pubescent and fully adult rhesus monkeys were subjected to 6,000 rads of fractionated supervoltage X-irradiation, and the difference of these two age groups in clinical and neuropathological changes after the irradiation was studied. The pubescent monkey was more vulnerable to irradiation than the fully adult monkey, and showed more clinical signs and more focal lesions of delayed brain damage from radiation. (author)

  6. Cloning and Comparison of Factor X from Rhesus Monkey (Macaca mulatta)

    OpenAIRE

    Chen, Younan; Qin, Shengfang; Tan, Weidong; Lu, Yanrong; Jie ZHANG; Li, Hongxia; Bu, Hong; Cheng, Jingqiu

    2009-01-01

    The reliability of the rhesus monkey as an important experimental animal depends on its genetic concordance with human. During our assessment of the rhesus monkey as a preclinical model for coagulation-related research, we cloned the full-length cDNA of rhesus monkey factor X (FX) and compared its genetic characteristics and coagulation activity with those of human FX. The full-length cDNA of rhesus monkey FX was 1683 bp in length, corresponding to 487 coding amino acids and sharing 94.71% nu...

  7. Direct demonstration of retroviral recombination in a rhesus monkey.

    OpenAIRE

    Wooley, D P; Smith, R A; Czajak, S; Desrosiers, R C

    1997-01-01

    Recombination may be an important mechanism for increasing variation in retroviral populations. Retroviral recombination has been demonstrated in tissue culture systems by artificially creating doubly infected cells. Evidence for retroviral recombination in vivo is indirect and is based principally on the identification of apparently mosaic human immunodeficiency virus type 1 genomes from phylogenetic analyses of viral sequences. We infected a rhesus monkey with two different molecularly clon...

  8. Whole-Genome Transcription Profiling of Rhesus Monkey Rhadinovirus

    OpenAIRE

    DITTMER, DIRK P; Gonzalez, Carlos M.; Vahrson, Wolfgang; DeWire, Scott M.; Hines-Boykin, Rebecca; Damania, Blossom

    2005-01-01

    Rhesus monkey rhadinovirus (RRV) and Kaposi's sarcoma-associated herpesvirus (KSHV; also called human herpesvirus 8) belong to the gamma-2 grouping of herpesviruses. RRV and KSHV share a high degree of sequence similarity, and their genomes are organized in a similar fashion. RRV serves as an excellent animal model system to study the gamma herpesvirus life cycle both in vitro and in vivo. We have developed a high-sensitivity, high-throughput, high-specificity real-time quantitative reverse t...

  9. Biological Rhythms and Temperature Regulation in Rhesus Monkeys During Spaceflight

    Science.gov (United States)

    Fuller, Charles A. (Principal Investigator)

    1996-01-01

    This program examined the influence of microgravity on temperature regulation and circadian timekeeping systems in Rhesus monkeys. Animals flown on the Soviet Biosatellite COSMOS 2229 were exposed to 11 2/3 days of microgravity. The circadian patterns temperature regulation, heart rate and activity were monitored constantly. This experiment has extended previous observations from COSMOS 1514 and 2044, as well as provided insights into the physiological mechanisms that produce these changes.

  10. Neurochemical Phenotypes of Myenteric Neurons in the Rhesus Monkey

    OpenAIRE

    Noorian, Ali Reza; Taylor, Georgia M.; Annerino, Dana M.; Greene, James G.

    2011-01-01

    Understanding the neurochemical composition of the enteric nervous system (ENS) is critical for elucidating neurological function in the gastrointestinal (GI) tract in health and disease. Despite their status as the closest models of human neurological systems, relatively little is known about enteric neurochemistry in nonhuman primates. We describe neurochemical coding of the enteric nervous system, specifically the myenteric plexus, of the rhesus monkey (Macaca mulatta) by immunohistochemis...

  11. Rhesus Monkeys Behave As If They Perceive the Duncker Illusion

    OpenAIRE

    Zivotofsky, A. Z.; Goldberg, M. E.; Powell, K. D.

    2005-01-01

    The visual system uses the pattern of motion on the retina to analyze the motion of objects in the world, and the motion of the observer him/herself. Distinguishing between retinal motion evoked by movement of the retina in space and retinal motion evoked by movement of objects in the environment is computationally difficult, and the human visual system frequently misinterprets the meaning of retinal motion. In this study, we demonstrate that the visual system of the Rhesus monkey also misint...

  12. Spontaneous number representation in semi-free-ranging rhesus monkeys.

    OpenAIRE

    Hauser, M D; Carey, S; Hauser, L B

    2000-01-01

    Previous research has shown that animals possess considerable numerical abilities. However, this work was based on experiments involving extensive training, a small number of captive subjects and relatively artificial testing procedures. We present the results of experiments on over 200 semi-free-ranging rhesus monkeys using a task which involves no training and mimics a natural foraging problem. The subjects observed two experimenters place pieces of apple, one at a time, into each of two op...

  13. Accelerated structural decrements in the aging female rhesus macaque lung compared with males

    OpenAIRE

    Herring, Matt J.; Avdalovic, Mark V.; Quesenberry, Cheryl L.; Putney, Lei F.; Tyler, Nancy K.; Ventimiglia, Frank F.; St. George, Judith A.; Hyde, Dallas M.

    2012-01-01

    Aging is associated with morphometric changes in the lung that lead to decreased lung function. The nonhuman primate lung has been shown to have similar architectural, morphological, and developmental patterns to that of humans. We hypothesized that the lungs of rhesus monkeys age in a pattern similar to human lungs. Thirty-four rhesus monkeys from the California National Primate Research Center were euthanized, necropsied, and the whole lungs sampled. Stereological analysis was performed to ...

  14. Risky business: Rhesus monkeys exhibit persistent preferences for risky options

    Directory of Open Access Journals (Sweden)

    EricRXu

    2014-04-01

    Full Text Available Rhesus monkeys appear to prefer risky over safe options in experiential decision-making tasks. These findings might be due, however, to specific contextual factors in the tasks used to date, such as a large number of successive trials and small ‘stakes’, i.e., small amounts of fluid reward. In the present experiment, we increased the stakes and used a small number of trials in order to explore the generality of risky decision-making in monkeys. We found a consistent preference for risky options, except when the expected value of the safe option was greater than the risky option. Thus, with equivalent mean utilities between the safe and risky options, rhesus monkeys appear to have a robust preference for the risky options in a broad range of circumstances, akin to the preferences found in human children and some adults in similar tasks. One account for this result is that monkeys make their choices based on the salience of the largest payoff, without integrating likelihood and value across trials. A related idea is that they fail to override an impulsive tendency to select the option with the potential to obtain the highest possible payoff. Our results rule out both accounts and contribute to an understanding of the diversity of risky decision-making among primates.

  15. Early adversity contributes to chronic stress induced depression-like behavior in adolescent male rhesus monkeys.

    Science.gov (United States)

    Zhang, Zhi-Yi; Mao, Yu; Feng, Xiao-Li; Zheng, Na; Lü, Long-Bao; Ma, Yuan-Ye; Qin, Dong-Dong; Hu, Xin-Tian

    2016-06-01

    Chronic stress is an important cause for depression. However, not everyone who is exposed to chronic stress will develop depression. Our previous studies demonstrated that early adversity can cause lasting changes in adolescent rhesus monkeys, but depressive symptoms have not been observed. Compared to adults, it is still unknown that whether adolescent rhesus monkeys experiencing early adversity are more likely to develop depressive symptoms. In this study, we investigated the long term relationship between early adversity, chronic stress and adolescent depression for the first time. Eight male rhesus monkeys were reared in maternal separation (MS) or mother-reared (MR) conditions. All of them went through unpredictable chronic stress for two months at their age four. The stressors included space restriction, intimidation, long illumination and fasting. Behavioral and physiological data were collected during the experiment. The results showed that, compared with the MR group, the locomotor activity of MS group was significantly decreased after one month of chronic stress while huddling up and stereotypical behaviors were significantly increased. Moreover, this trend continued and even worsened at the second month. Significantly higher hair cortisol levels and lower body weight were observed in MS group after two months of stress. These results indicate that early adversity is one of the environmental factors which can increase the susceptibility of depression when experiencing chronic stress in the later life. This will further clarify the important roles of early environmental factors in the development of adolescent depression and children rearing conditions should receive more attention. PMID:27025444

  16. Endocrine responses in the rhesus monkey during acute cold exposure

    Energy Technology Data Exchange (ETDEWEB)

    Lotz, W.G.; Saxton, J.L. (Naval Aerospace Medical Research Lab., Pensacola, FL (United States))

    1991-03-11

    The authors studied five young male rhesus monkeys (Macaca mulatta), 3.4 to 6.7 kg, to determine the relationship between fluid balance hormones and urine production during acute, dry cold exposure. Each monkey served as its own control in duplicate experimental sessions at 6C or 26C. A 6-h experimental session consisted of 120 min equilibration at 26C, 120 min experimental exposure, and 120 min recovery at 26C. Urinary and venous catheters were inserted on the morning of a session. Rectal (Tre) and skin temperatures were monitored continuously. Blood samples were taken at 0, 30, 60 and 120 min of exposure, and at 60 min postexposure. Plasma was analyzed for arginine vasopressin (AVP), atrial natriuretic factor (ANF), plasma renin activity (PRA), plasma aldosterone (PA), and osmolality. Urine samples were analyzed for osmolality, electrolytes, and creatinine. Mean Tre was 1.6C lower after 120 min at 6C than at 26C. Urine volume and osmolality were not altered by cold exposure, as they are in humans and rats. Vasopressin and PA increased sharply, with mean plasma levels in monkeys exposed to cold more than threefold and tenfold, respectively, the levels in monkeys exposed at 26C. In contrast, ANF, PRA, and plasma osmolality were not significantly changed by cold exposure. The absence of a cold-induced diuresis in the monkey may be related to the marked increase in plasma AVP level.

  17. Analysis of liver pathology in captive rhesus monkeys at different ages%不同年龄实验恒河猴自然死亡的肝脏病变谱分析

    Institute of Scientific and Technical Information of China (English)

    赵玺龙; 李学锋; 陈玥; 宋蜀伶; 李锋; 蔡琳; 杨举伦

    2011-01-01

    Objective To observe the pathological changes in the livers of captive rhesus monkeys, and explore their distribution rule and provide basic background reference data for relevant biomedical studies. Methods One hundred and fifty five natularly dead rhesus monkeys were recorded in our department from 1998 to 2008 years. Autopsy was performed and the pathological changes in the livers were examined and statistically analyzed according to different ages at 2 to 20 years. Results Of the 155 monkeys, 88 animals had liver lesions (56.7%). The main lesions included hepatocyte degeneration, hepatocyte necrosis, inflammatory cell infiltration, macrophage hyperplasia, liver congestion, collagen fiber hyperplasia, liver abscess, parasites, etc. Among those lesions the incidence rate of hepatocyte degeneration was the highest (34. 19% ). The chi-square test shows that in the adult groups, the incidence rate of hydropic degeneration was significantly higher than that in the juvenile group, and the incidence rates of fatty degeneration, mild inflammatory cell infiltration and fibroblastic proliferation in the old age group were significantly higher than that in the juvenile and adult groups (P <0.05). Conclusions The incidence rates of spontaneous liver diseases in breeding rhesus macaques are rather high. The frequencies of hepatic pathological changes are correlated with the age of the monkeys. Attention should be paid to the spontaneous hepatic lesions when we study the liver pathology in rhesus monkeys, and old rhesus monkeys should not be used in drug safety evaluation. The results of our study provide important information of the captive monkeys, useful in quality control of captive monkeys and animal tests.%目的 观察人工饲养条件下实验恒河猴肝脏病理改变,探讨肝脏疾病分布规律和病理改变特点,丰富实验猴自发病变基本研究资料.方法 对1998~2008年云南地区饲养的自然死亡的155只恒河猴(年龄2~20岁)的

  18. Myeloid-Lymphoid Ontogeny in the Rhesus Monkey (Macaca mulatta)

    OpenAIRE

    Batchelder, Cynthia A.; Duru, Nadire; Lee, C. Chang I.; Baker, Chris A.R.; Swainson, Louise; McCune, Joseph M; Tarantal, Alice F

    2014-01-01

    Establishment of a functional immune system has important implications for health and disease, yet questions remain regarding the mechanism, location, and timing of development of myeloid and lymphoid cell compartments. The goal of this study was to characterize the ontogeny of the myeloid-lymphoid system in rhesus monkeys to enhance current knowledge of the developmental sequence of B cell (CD20, CD79), T cell (CD3, CD4, CD8, FoxP3), dendritic cell (CD205), and macrophage (CD68) lineages in ...

  19. Individual differences in rhesus monkeys' demand for drugs of abuse.

    Science.gov (United States)

    Koffarnus, Mikhail N; Hall, Amy; Winger, Gail

    2012-09-01

    A relatively small percentage of humans who are exposed to drugs of abuse eventually become addicted to or dependent on those drugs. These individual differences in likelihood of developing drug addiction may reflect behavioral, neurobiological or genetic correlates of drug addiction and are therefore important to model. Behavioral economic measures of demand establish functions whose overall elasticity (rate of decrease in consumption as price increases) reflects the reinforcing effectiveness of various stimuli, including drugs. Using these demand functions, we determined the reinforcing effectiveness of five drugs of abuse (cocaine, remifentanil, ketamine, methohexital and ethanol) in 10 rhesus monkeys with histories of intravenous drug-taking. There was a continuum of reinforcing effectiveness across the five drugs, with cocaine and remifentanil showing the most reinforcing effectiveness. There was also a continuum of sensitivity of the monkeys; two of the 10 animals, in particular, showed greater demand for the drugs than did the remaining eight monkeys. In addition, monkeys that demonstrated greater demand for one drug tended to show greater demand for all drugs but did not show a similar relatively greater demand for sucrose pellets. These findings suggest that the tendency to find drugs to be reinforcing is a general one, not restricted to particular drugs and also, that a minority of animals show a substantially enhanced sensitivity to the reinforcing effects of drugs. The possibility that differences in responsiveness to the reinforcing effects of drugs may form the basis of individual differences in drug-taking in humans should be considered. PMID:21762288

  20. Application and Assessment of Ketamine-Xylidinothiazoline Combinations for Anaesthesia in Rhesus Monkey

    Institute of Scientific and Technical Information of China (English)

    XIAO Jianhua; GAO Li; Liu Huanqi; FAN Honggang; MA Haikun; LIU Yun; WANG Hongbin

    2009-01-01

    The quantitative anaesthesia assessment technique was used to evaluate the effectiveness of ketamine, ketaminexylidinothiazoline in rhesus monkey. Total 20 healthy adult rhesus monkeys were divided into two groups and anaesthetized anaesthesia rectal temperature, respiratory rate, heart rate, saturation of blood oxygen and blood pressure were recorded. The degree of sedation, analgesia, muscle relaxation were monitored either. The results showed that ketamine alone did not produce adequate anaesthesia, and the combination of xylidinothiazoline and ketamine provided adequate anesthesia for rhesus monkeys with no significant side effects and little effects on respiration and circulation.

  1. Infection and Persistence of Rhesus Monkey Rhadinovirus in Immortalized B-Cell Lines

    OpenAIRE

    Bilello, John P.; Lang, Sabine M.; Wang, Fred; Aster, Jon C.; Desrosiers, Ronald C.

    2006-01-01

    Similar to its close relative human herpesvirus 8, rhesus monkey rhadinovirus (RRV) persists predominantly in B cells of its natural host. Rhesus monkey B-cell lines immortalized by the Epstein-Barr-related virus from rhesus monkeys (rhEBV) were used as targets for infection by RRV. These cultured B cells were susceptible to infection by RRV and continued to produce low titers of RRV for months of continuous culture. Infection by RRV did not detectably alter the growth rates of these B-cell l...

  2. Intranasal oxytocin enhances socially-reinforced learning in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Lisa A Parr

    2014-09-01

    Full Text Available There are currently no drugs approved for the treatment of social deficits associated with autism spectrum disorders (ASD. One hypothesis for these deficits is that individuals with ASD lack the motivation to attend to social cues because those cues are not implicitly rewarding. Therefore, any drug that could enhance the rewarding quality of social stimuli could have a profound impact on the treatment of ASD, and other social disorders. Oxytocin (OT is a neuropeptide that has been effective in enhancing social cognition and social reward in humans. The present study examined the ability of OT to selectively enhance learning after social compared to nonsocial reward in rhesus monkeys, an important species for modeling the neurobiology of social behavior in humans. Monkeys were required to learn an implicit visual matching task after receiving either intranasal (IN OT or Placebo (saline. Correct trials were rewarded with the presentation of positive and negative social (play faces/threat faces or nonsocial (banana/cage locks stimuli, plus food. Incorrect trials were not rewarded. Results demonstrated a strong effect of socially-reinforced learning, monkeys’ performed significantly better when reinforced with social versus nonsocial stimuli. Additionally, socially-reinforced learning was significantly better and occurred faster after IN-OT compared to placebo treatment. Performance in the IN-OT, but not Placebo, condition was also significantly better when the reinforcement stimuli were emotionally positive compared to negative facial expressions. These data support the hypothesis that OT may function to enhance prosocial behavior in primates by increasing the rewarding quality of emotionally positive, social compared to emotionally negative or nonsocial images. These data also support the use of the rhesus monkey as a model for exploring the neurobiological basis of social behavior and its impairment.

  3. Hippocampal formation lesions produce memory impairment in the rhesus monkey.

    Science.gov (United States)

    Beason-Held, L L; Rosene, D L; Killiany, R J; Moss, M B

    1999-01-01

    There is much debate over the role of temporal lobe structures in the ability to learn and retain new information. To further assess the contributions of the hippocampal formation (HF), five rhesus monkeys received stereotactically placed ibotenic acid lesions of this region without involvement of surrounding ventromedial temporal cortices. After surgery, the animals were trained on two recognition memory tasks: the Delayed Non-Match to Sample (DNMS) task, which tests the ability to remember specific trial unique stimuli, and the Delayed Recognition Span Task (DRST), which tests the ability to remember an increasing array of stimuli. Relative to normal control monkeys, those with HF lesions demonstrated significant impairments in both learning and memory stages of the DNMS task. Additionally, the HF group was significantly impaired on spatial, color, and object versions of the DRST. Contrary to suggestions that damage to the entorhinal and parahippocampal cortices is required to produce significant behavioral deficits in the monkey, these results demonstrate that selective damage to the HF is sufficient to produce impairments on tasks involving delayed recognition and memory load. This finding illustrates the importance of the HF in the acquisition and retention of new information. PMID:10560927

  4. Mirror-induced self-directed behaviors in rhesus monkeys after visual-somatosensory training.

    Science.gov (United States)

    Chang, Liangtang; Fang, Qin; Zhang, Shikun; Poo, Mu-ming; Gong, Neng

    2015-01-19

    Mirror self-recognition is a hallmark of higher intelligence in humans. Most children recognize themselves in the mirror by 2 years of age. In contrast to human and some great apes, monkeys have consistently failed the standard mark test for mirror self-recognition in all previous studies. Here, we show that rhesus monkeys could acquire mirror-induced self-directed behaviors resembling mirror self-recognition following training with visual-somatosensory association. Monkeys were trained on a monkey chair in front of a mirror to touch a light spot on their faces produced by a laser light that elicited an irritant sensation. After 2-5 weeks of training, monkeys had learned to touch a face area marked by a non-irritant light spot or odorless dye in front of a mirror and by a virtual face mark on the mirroring video image on a video screen. Furthermore, in the home cage, five out of seven trained monkeys showed typical mirror-induced self-directed behaviors, such as touching the mark on the face or ear and then looking at and/or smelling their fingers, as well as spontaneously using the mirror to explore normally unseen body parts. Four control monkeys of a similar age that went through mirror habituation but had no training of visual-somatosensory association did not pass any mark tests and did not exhibit mirror-induced self-directed behaviors. These results shed light on the origin of mirror self-recognition and suggest a new approach to studying its neural mechanism. PMID:25578908

  5. Video-task acquisition in rhesus monkeys (Macaca mulatta) and chimpanzees (Pan troglodytes): a comparative analysis

    Science.gov (United States)

    Hopkins, W. D.; Washburn, D. A.; Hyatt, C. W.; Rumbaugh, D. M. (Principal Investigator)

    1996-01-01

    This study describes video-task acquisition in two nonhuman primate species. The subjects were seven rhesus monkeys (Macaca mulatta) and seven chimpanzees (Pan troglodytes). All subjects were trained to manipulate a joystick which controlled a cursor displayed on a computer monitor. Two criterion levels were used: one based on conceptual knowledge of the task and one based on motor performance. Chimpanzees and rhesus monkeys attained criterion in a comparable number of trials using a conceptually based criterion. However, using a criterion based on motor performance, chimpanzees reached criterion significantly faster than rhesus monkeys. Analysis of error patterns and latency indicated that the rhesus monkeys had a larger asymmetry in response bias and were significantly slower in responding than the chimpanzees. The results are discussed in terms of the relation between object manipulation skills and video-task acquisition.

  6. Dose-response data for X-ray induced translocations in spermatogonia of rhesus monkeys

    International Nuclear Information System (INIS)

    The yields of translocations in spermatocytes after irradiation of spermatogonia of Rhesus monkeys with doses of 100, 220, or 300 rad X-rays were low and consistent with a humped dose-response curve with a peak at about 200 rad. Such a curve would agree well with earlier results on the marmoset and man, but the yields at any dose in the Rhesus monkey were lower

  7. Preference in rhesus monkeys given a choice between cocaine and d,l-cathinone.

    OpenAIRE

    Woolverton, W L; Johanson, C E

    1984-01-01

    Previous experiments have shown that both cocaine and d,l-cathinone can function as positive reinforces when delivered intravenously to rhesus monkeys. However, the relative reinforcing efficacies of these compounds have not been established. In the present experiment, three rhesus monkeys were allowed to choose between saline and several doses of d,l-cathinone or cocaine as well as between several doses of both drugs in a discrete-trial choice procedure. Sufficient doses (.05 to .2 mg/kg/inj...

  8. Effects of Vestibular Prosthesis Electrode Implantation and Stimulation on Hearing in Rhesus Monkeys

    OpenAIRE

    Dai, Chenkai; Fridman, Gene Y.; Della Santina, Charles C.

    2010-01-01

    To investigate the effects of vestibular prosthesis electrode implantation and activation on hearing in rhesus monkeys, we measured auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE) in four rhesus monkeys before and after unilateral implantation of vestibular prosthesis electrodes in each of 3 left semicircular canals (SCC). Each of the 3 left SCCs were implanted with electrodes via a transmastoid approach. Right ears, which served as controls, were not s...

  9. Rhesus monkey is a new model of secondary lymphedema in the upper limb

    OpenAIRE

    Wu, Guojun; Xu, Hao; Zhou, Wenhong; Yuan, Xianshun; Yang, Zhe; Yang, Qing; Ding, Feng; Meng, Zhigang; Liang, Weili; Geng, Chong; Gao, Ling; Tian, Xingsong

    2014-01-01

    Objective: This study is to establish the rhesus monkey model of lymphedema in the upper limbs, and assess the suitability of this model. Methods: An animal model of lymphedema was established by the combined irradiation and surgical techniques in the upper limbs of these rhesus monkeys. Physical examination, high-resolution MR lymphangiography, bioelectrical impedance analysis (BIA), and immunohistochemical staining were performed to determine the severity of the edema in the upper limbs of ...

  10. Recognizing Facial Cues: Individual Discrimination by Chimpanzees (Pan troglodytes) and Rhesus Monkeys (Macaca mulatta)

    OpenAIRE

    Parr, Lisa A.; Winslow, James T.; Hopkins, William D.; de Waal, Frans B. M.

    2000-01-01

    Faces are one of the most salient classes of stimuli involved in social communication. Three experiments compared face-recognition abilities in chimpanzees (Pan troglodytes) and rhesus monkeys (Macaca mulatta). In the face-matching task, the chimpanzees matched identical photographs of conspecifics' faces on Trial 1, and the rhesus monkeys did the same after 4 generalization trials. In the individual-recognition task, the chimpanzees matched 2 different photographs of the same individual afte...

  11. Multidrug-Resistant Proteus mirabilis Isolated From Newly Weaned Infant Rhesus Monkeys and Ferrets

    OpenAIRE

    Yu, Wenhai; He, Zhanlong; Huang, Fen

    2015-01-01

    Background: Proteus mirabilis is an important uropathogen that causes complicated Urinary Tract Infection (UTI) and induces diarrhea in infants. Objectives: This study aimed to investigate P. mirabilis infection in newly weaned infant rhesus monkeys (Macaca mulatta) and ferrets (Mustela putorius furo) with diarrhea. Materials and Methods: Stool samples were collected from 74 rhesus monkeys and 12 ferrets with diarrhea. Proteus mirabilis was isolated from the samples through Polymerase Chain R...

  12. Exposure to sunlight reduces the risk of myopia in rhesus monkeys.

    Directory of Open Access Journals (Sweden)

    Yong Wang

    Full Text Available Exposure to sunlight has recently been postulated as responsible for the effect that more time spent outdoors protects children from myopia, while early life exposure to natural light was reported to be possibly related to onset of myopia during childhood. In this study, we had two aims: to determine whether increasing natural light exposure has a protective effect on hyperopic defocus-induced myopia, and to observe whether early postnatal exposure to natural light causes increased risk of refractive error in adolescence. Eight rhesus monkeys (aged 20-30 days were treated monocularly with hyperopic-defocus (-3.0D lens and divided randomly into two groups: AL group (n=4, reared under Artificial (indoor Lighting (08:00-20:00; and NL group (n=4, exposed to Natural (outdoor Light for 3 hours per day (11:00-14:00, and to indoor lighting for the rest of the light phase. After being reared with lenses for ca. 190 days, all monkeys were returned to unrestricted vision until the age of 3 years. Another eight age-matched monkeys, reared with unrestricted vision under artificial lighting since birth, were employed as controls. The ocular refraction, corneal curvature and axial dimensions were measured before lens-wearing (at 23±3 days of age, monthly during the light phase, and at the age of puberty (at 1185+3 days of age. During the lens-wearing treatment, infant monkeys in the NL group were more hyperopic than those in the AL group (F=5.726, P=0.032. Furthermore, the two eyes of most NL monkeys remained isometropic, whereas 3 of 4 AL monkeys developed myopic anisometropia more than -2.0D. At adolescence, eyes of AL monkeys showed significant myopic anisometropia compared with eyes of NL monkeys (AL vs NL: -1.66±0.87D vs -0.22±0.44D; P=0.002 and controls (AL vs Control: -1.66±0.87D vs -0.05±0.85D; P<0.0001. All differences in refraction were associated with parallel changes in axial dimensions. Our results suggest that exposure to natural outdoor

  13. Multidrug-Resistant Proteus mirabilis Isolated From Newly Weaned Infant Rhesus Monkeys and Ferrets

    OpenAIRE

    Yu,; He; Huang

    2015-01-01

    Background Proteus mirabilis is an important uropathogen that causes complicated Urinary Tract Infection (UTI) and induces diarrhea in infants. Objectives This study aimed to investigate P. mirabilis infection in newly weaned infant rhesus monkeys (Macaca mulatta) and ferrets (Mustela putorius furo) with diarrhea. Materials and Methods Stool samples were collected from 74 rhesus mo...

  14. Effects of maternal mobility, partner, and endocrine state on social responsiveness of adolescent rhesus monkeys.

    Science.gov (United States)

    Anderson, C O; Kenney, A M; Mason, W A

    1977-09-01

    The social behavior of rhesus monkeys raised for the 1st year of life with mobile (MS) or stationary (SS) cloth surrogate mothers was investigated when the animals reached 4-5 yr of age. The MS males generally refrained from social interaction during initial pairings with females, whereas SS males interacted frequently, but were more often the targets of attacks and chases from adult females than were MS males. The MS males were more likely to vary their social behavior according to the behavior of the social partner and seemed to benefit more from extended social exposure than their SS counterparts. The MS females were more similar to wild-born females than were SS females in nearly every behavior category and dimension tested. These results suggest that rearing with mobile artificial mothers improves the chances of later adaptive social adjustments in socially restricted monkeys. PMID:410688

  15. Expression of pax-6 in rhesus monkey of optical defocus induced myopia and form deprivation myopia

    Institute of Scientific and Technical Information of China (English)

    钟兴武; 葛坚; 邓文国; 陈晓莲; 黄娟

    2004-01-01

    Background Pax-6 gene plays an important role in the process of eye development. This study was to determine the role of pax-6 in the axial myopia produced by hyperopic optical defocus and form deprivation in infant monkeys. Methods Among seven normal infant rhesus monkeys (aged 1 to 1.5 months), five wore -3.00 D spectacle lenses over their right eyes and zero-powered lenses over their left eyes. Monocular form deprivation was produced by eyelid fusion in two monkeys. Ten weeks later, the monkeys were sacrificed by an overdose of barbiturates and their eyes were removed immediately. A 5 mm×5 mm button of retina and sclera was taken from the posterior poles along with a 4-mm optic nerve. RNA was isolated separately from each of these three types of tissues. After that, reverse transcription polymerase chain reaction (RT-PCR) was used for determining gene expression in the retina, sclera and optic nerve. Semi-quantitative analyses were performed on the PCR products. Results As expected, the optically induced hyperopic defocus and the form deprivation produced myopic growth. For the lens-treatment monkeys, pax-6 gene expression in the retinas of the defocused eyes was significantly higher than in the retinas of the left eyes (t=5.703, P=0.005). However, there were no analogous significant differences between pax-6 expression in the scleras or the optic nerves. For the two form-deprived monkeys, there were no obvious differences in pax-6 gene expression in the retinas or the optic nerves. Conclusion The result that the expression of pax-6 was enhanced by hyperopic defocus in the infant monkey retina suggests that pax-6 may be involved in vision-dependent eye growth and emmetropization.

  16. Two processes support visual recognition memory in rhesus monkeys.

    Science.gov (United States)

    Guderian, Sebastian; Brigham, Danielle; Mishkin, Mortimer

    2011-11-29

    A large body of evidence in humans suggests that recognition memory can be supported by both recollection and familiarity. Recollection-based recognition is characterized by the retrieval of contextual information about the episode in which an item was previously encountered, whereas familiarity-based recognition is characterized instead by knowledge only that the item had been encountered previously in the absence of any context. To date, it is unknown whether monkeys rely on similar mnemonic processes to perform recognition memory tasks. Here, we present evidence from the analysis of receiver operating characteristics, suggesting that visual recognition memory in rhesus monkeys also can be supported by two separate processes and that these processes have features considered to be characteristic of recollection and familiarity. Thus, the present study provides converging evidence across species for a dual process model of recognition memory and opens up the possibility of studying the neural mechanisms of recognition memory in nonhuman primates on tasks that are highly similar to the ones used in humans. PMID:22084079

  17. Pharmacokinetics and disposition of WR-1065 in the rhesus monkey

    International Nuclear Information System (INIS)

    The pharmacokinetics of WR-1065 [S-2-(3-aminopropylamino)ethanethiol] were investigated following iv, intraduodenal, and intraportal administrations in the rhesus monkey. Pharmacokinetic parameters were estimated by compartmental modeling of plasma concentration data from 10-min and 120-min iv infusions. Higher apparent volumes of distribution (Vc and Vss) and higher mean residence time (MRT) were observed at the slower infusion rate but a constant total dose. The values reflect a change in the distribution of WR-1065, possibly due to to saturation of binding in plasma and tissue. However, clearance remained unchanged. For a monkey administered approximately twice the 60 mg/kg dose infused over 120 min, data analysis indicates a disproportional increase in AUC and a substantial decrease in clearance. Low and erratic plasma concentrations of free drug (analytically determined without reductive cleavage) were observed following intraduodenal administration of WR-1065, demonstrating the drug's poor oral bioavailability. Results of intraduodenal administrations of radiolabeled drug indicated than an appreciable amount of the radiolabel in the dose reached the systemic circulation. However, after either intraduodenal or iv administration, only 31% of the AUC (radiolabel) could be accounted for as total (free and disulfide-bound) WR-1065 by specific analysis in separate experiments. Low levels of total cysteamine strongly suggest it to be a minor contributor to the disposition of the drug. Free WR-1065 AUC values following intraportal administration were similar to values obtained after iv administration

  18. Movement Limitation and Immune Responses of Rhesus Monkeys

    Science.gov (United States)

    Sonnenfeld, Gerald; Morton, Darla S.; Swiggett, Jeanene P.; Hakenewerth, Anne M.; Fowler, Nina A.

    1993-01-01

    The effects of restraint on immunological parameters was determined in an 18 day ARRT (adult rhesus restraint test). The monkeys were restrained for 18 days in the experimental station for the orbiting primate (ESOP), the chair of choice for Space Shuttle experiments. Several immunological parameters were determined using peripheral blood, bone marrow, and lymph node specimens from the monkeys. The parameters included: response of bone marrow cells to GM-CSF (granulocyte-macrophage colony stimulating factor), leukocyte subset distribution, and production of IFN-alpha (interferon-alpha) and IFN-gamma (interferon-gamma). The only parameter changed after 18 days of restraint was the percentage of CDB+ T cells. No other immunological parameters showed changes due to restraint. Handling and changes in housing prior to the restraint period did apparently result in some restraint-independent immunological changes. Handling must be kept to a minimum and the animals allowed time to recover prior to flight. All experiments must be carefully controlled. Restraint does not appear to be a major issue regarding the effects of space flight on immune responses.

  19. Human-Rhesus Monkey conflict at Rampur Village under Monohardi Upazila in Narsingdi District of Bangladesh

    Directory of Open Access Journals (Sweden)

    M.F. Ahsan

    2014-06-01

    Full Text Available Human-Rhesus monkey conflicts were recorded at Rampur Village under Khidirpur Union Parishad of Monohardi upazila under Narsingdi District in Bangladesh from April to September 2012. There were three groups of Rhesus monkeys living in the area. The focal study group comprised 26 individuals (4 adult males, 6 adult females, 10 juveniles and 6 infants. The monkeys consumed parts of 10 plant species. From the questionnaire survey, it was found that the greatest damage caused by monkeys was on betel leaf vines and the least damage on vegetables. Eighty percent respondents opted to conserve the monkeys and 20% opined status quo. Some restricted areas (especially khas lands may be identified and planted with some fruit trees for survival of monkeys and for reducing conflicts with humans.

  20. Influence of prenatal iron deficiency and MAOA genotype on response to social challenge in rhesus monkey infants

    OpenAIRE

    Golub, Mari S.; Hogrefe, Casey E.; Unger, Erica L.

    2012-01-01

    Social and emotional behavior are known to be sensitive to both developmental iron deficiency and monoamine oxidase A (MAOA) gene polymorphisms. In this study, male rhesus monkey infants deprived of dietary iron in utero (ID) were compared to iron sufficient (IS) controls (n=10/group). Half of each group had low MAOA activity genotypes and half had high MAOA activity genotypes. A series of social response tests were conducted at 3 to 14 months of age. MAOA genotype influenced attention to a v...

  1. Simian virus 40-induced disease in rhesus monkeys with simian acquired immunodeficiency syndrome.

    OpenAIRE

    Horvath, C J; Simon, M A; Bergsagel, D. J.; Pauley, D. R.; King, N W; Garcea, R L; Ringler, D. J.

    1992-01-01

    Simian virus 40 (SV40) disease was diagnosed in four rhesus monkeys that died with SIV-induced acquired immunodeficiency syndrome (AIDS). One juvenile monkey seroconverted for SV40 6 months after inoculation with SIV and developed severe bilateral tubulointerstitial nephritis. In contrast, progressive multifocal leukoencephalopathy (PML) occurred in two adult monkeys that were seropositive for SV40 before SIV inoculation, as well as a third adult that was naturally infected with SIV and serop...

  2. Circulation of Campylobacter spp. in rhesus monkeys (Macaca mulatta held in captivity: a longitudinal study

    Directory of Open Access Journals (Sweden)

    Márcia Cristina Ribeiro Andrade

    2007-02-01

    Full Text Available Campylobacteriosis is an extremely important zoonosis, circulating freely in the environment. In nonhuman primates kept in open facilities and bred for experimental purposes, the presence of Campylobacter spp. could cause severe damage to the production and interfere with the results of scientific research. In this paper, we assessed the circulation of Campylobacter spp. in a colony of clinically healthy rhesus monkeys (Macaca mulatta destined to research. The analysis was carried out during seven non-consecutive years. Data showed that despite several changes made in animal management along the studied years in order to control this zoonosis, reduction of bacterial charge did not occur. Significant differences among the age groups and sex were observed. Infants showed higher susceptibility than adult animals. In general males were more infected than females. Modifications adopted in the handling techniques need to be reviewed with the intent of improving the production, reducing bacterial infection of the stock and avoiding undesirable cross reactions in the research carried out with these animals. Therefore, this paper alerts professionals that work directly with captive rhesus monkeys about the risks of Campylobacter spp. infection and possible interference on the experimental procedures.

  3. Lifetime effects of single-event proton exposures in rhesus monkeys

    International Nuclear Information System (INIS)

    The US School of Aerospace Medicine studies of the lifetime effects of proton irradiation in rhesus monkeys have been conducted. Life-span shortening has been associated with proton energies of 55 MeV and above, as well as with doses greater than 360 rads. Female rhesus monkeys have a higher mortality than males as a result of high incidence of endometriosis in the irradiated animals. A dose ordering effect is apparent. Mortality rates began to accelerate at eight years after doses of 360 to 400 rads; at two years, after 500 to 650 rads; and less than one year, after 800 rads. Malignant tumors accounted for 18% of the deaths in the proton-exposed animals. Endometriosis was the cause of 25% of the deaths in this group. Energy-specific effects were observed. Eight malignant brain tumors occurred in animals exposed to 55-MeV protons and in no other group. Cataract incidence was highest in animals exposed to 32 and 55 MeV. These observations suggest a positive relationship with the Bragg peak energy distribution in the area of the brain and crystalline lens. Glucose tolerance was lowest in the animals exposed to totally penetrating radiation, where the fraction of the surface dose reaching the pancreas was highest. Age-matched control animals have yet to pass their median survival time, and the colony continues to be a valuable source of data on the relationship of total-body radiation to age-related diseases in captive monkeys. 16 refs., 6 figs., 5 tabs

  4. Temporal discounting and inter-temporal choice in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Jaewon Hwang

    2009-06-01

    Full Text Available Humans and animals are more likely to take an action leading to an immediate reward than actions with delayed rewards of similar magnitudes. Although such devaluation of delayed rewards has been almost universally described by hyperbolic discount functions, the rate of this temporal discounting varies substantially among different animal species. This might be in part due to the differences in how the information about reward is presented to decision makers. In previous animal studies, reward delays or magnitudes were gradually adjusted across trials, so the animals learned the properties of future rewards from the rewards they waited for and consumed previously. In contrast, verbal cues have been used commonly in human studies. In the present study, rhesus monkeys were trained in a novel inter-temporal choice task in which the magnitude and delay of reward were indicated symbolically using visual cues and varied randomly across trials. We found that monkeys could extract the information about reward delays from visual symbols regardless of the number of symbols used to indicate the delay. The rate of temporal discounting observed in the present study was comparable to the previous estimates in other mammals, and the animal’s choice behavior was largely consistent with hyperbolic discounting. Our results also suggest that the rate of temporal discounting might be influenced by contextual factors, such as the novelty of the task. The flexibility furnished by this new inter-temporal choice task might be useful for future neurobiological investigations on inter-temporal choice in non-human primates.

  5. Metabolism of [75Se]selenite by rhesus monkeys

    International Nuclear Information System (INIS)

    The metabolism of [75Se]selenite was studied in rhesus monkeys. In blood samples taken various times after injection, Sephadex G-150 gel filtration revealed that the majority of the 75Se was associated with hemoglobin and low-molecular-weight compounds in erythrocytes up to 24 hours after selenium injection. Subsequently a gradual increase of 75Se occurred in glutathione peroxidase (GSH-Px) with a concurrent decrease of label with hemoglobin. In contrast to the erythrocytes, over 80% of the labeled selenium in plasma was associated with one peak 3 hours and later after injection. This major protein eluted at a position similar to GSH-Px on gel filtration, but subsequent chromatography on diethylaminoethyl (DEAE)-Sephacel separated the radiolabeled protein from GSH-Px. Gel filtration of heart, muscle, brain and pancreas cytosol revealed two major selenium-containing proteins, whereas one was predominant in liver and kidney. The major selenium peak was associated with GSH-Px in liver but not in the kidney. GSH-Px activity with either organic or inorganic peroxides as substrates and glutathione transferase activity were higher in liver than kidney

  6. Metabolism of (75Se)selenite by rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Beilstein, M.A.; Butler, J.A.; Whanger, P.D.

    1984-08-01

    The metabolism of (75Se)selenite was studied in rhesus monkeys. In blood samples taken various times after injection, Sephadex G-150 gel filtration revealed that the majority of the 75Se was associated with hemoglobin and low-molecular-weight compounds in erythrocytes up to 24 hours after selenium injection. Subsequently a gradual increase of 75Se occurred in glutathione peroxidase (GSH-Px) with a concurrent decrease of label with hemoglobin. In contrast to the erythrocytes, over 80% of the labeled selenium in plasma was associated with one peak 3 hours and later after injection. This major protein eluted at a position similar to GSH-Px on gel filtration, but subsequent chromatography on diethylaminoethyl (DEAE)-Sephacel separated the radiolabeled protein from GSH-Px. Gel filtration of heart, muscle, brain and pancreas cytosol revealed two major selenium-containing proteins, whereas one was predominant in liver and kidney. The major selenium peak was associated with GSH-Px in liver but not in the kidney. GSH-Px activity with either organic or inorganic peroxides as substrates and glutathione transferase activity were higher in liver than kidney.

  7. Analysis of the virogenes related to the rhesus monkey endogenous type C retrovirus in monkeys and apes.

    OpenAIRE

    Tainsky, M A

    1981-01-01

    Molecular hybridization studies were carried out by using a [3H]complementary DNA (cDNA) probe to compare the endogenous type C retrovirus of rhesus monkeys (MMC-1) with other known retroviruses and related sequences in various primate DNAs. The genomic RNA of the endogenous type C retrovirus of stumptail monkeys (MAC-1) was found to be highly related to the MMC-1 cDNA probe, whereas the other retroviral RNAs tested showed no homology. Related sequences were found in Old World monkey DNAs and...

  8. Soluble human CD4 elicits an antibody response in rhesus monkeys that inhibits simian immunodeficiency virus replication

    International Nuclear Information System (INIS)

    Rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIVmac) demonstrate significant virologic and clinical improvement as a result of treatment with human recombinant soluble CD4 (rsCD4). The authors show that human rsCD4 does not efficiently inhibit SIVmac replication in bone marrow macrophages of rhesus monkeys and does not significantly augment bone marrow hematopoietic colony formation in vitro. However, plasma of human rsCD4-treated rhesus monkeys does exhibit significant anti-SIVmac activity in vitro. Plasma of these animals efficiently blocks SIVmac replicaton in peripheral blood lymphocytes and bone marrow macrophages. It also increases granulocyte/macrophage colony formation in vitro by bone marrow cells of SIVmac-infected monkeys. This plasma and the IgG fraction of plasma from a rhesus monkey immunized with human rsCD4 in adjuvant demonstrate reactivity with a soluble form of the rhesus monkey CD4 molecule, exhibit binding to CD4+ but not CD8+ concanavalin A-activated rhesus monkey peripheral blood lymphocytes, and precipitate the CD4 molecule from surface-labeled activated rhesus monkey peripheral blood lymphocytes. Moreover, anti-viral activity is demonstrable in the IgG fraction of plasma from a human rsCD4-immunized monkey. These studies raise the possibility that a modified human CD4 molecule serving as an immunogen might elicit an antibody response that could potentially induce a beneficial therapeutic response in human immunodeficiency virus-infected individuals

  9. Postnatal development of neuropeptide Y-like immunoreactivity in area 17 of normal and visually deprived rhesus monkeys.

    Science.gov (United States)

    Tigges, M; Tigges, J; McDonald, J K; Slattery, M; Fernandes, A

    1989-01-01

    Immunocytochemical methods were used to examine neuropeptide Y (NPY) immunoreactive neurons and fibers in area 17 of rhesus monkeys during the first year of life. NPY-immunoreactive (+) neurons are nonpyramidal cells which are either multipolar, bipolar, or bitufted in shape. They occur most frequently in layer 6 and the subjacent white matter, are sparser in the supragranular layers, and absent from layer 4C. Labeled somata in the supragranular layers are smaller compared to those in layer 6 and the white matter. A typical axon originates from the NPY+ soma or from a primary dendrite and frequently is varicose. Distribution and morphologies of NPY+ neurons in area 17 of infants are similar to those of adult monkeys. Thus, it seems that NPY+ neurons in rhesus monkeys are mature from birth. NPY+ fibers occur in area 17 from birth; however, they differ in density and distribution from those of older infant and adult monkeys. At birth, a prominent fiber plexus is found in the deepest part of layer 1, and another in the white matter. Immunoreactive processes are sparse in the remaining cortical gray, except for some vertical fibers extending from pia to white matter. By 4 months of age, labeled fibers form a coarse network in layers 2, 3, 5, and 6. In addition, a distinct plexus extends through layers 4B, 4A, and the lowest aspect of layer 3. Also, a thin immunoreactive fiber band is found at the bottom of layer 4C. In the remainder of layer 4C, NPY+ fibers are scant. The supragranular layers also exhibit a unique immunoreactive "snarl" of fibers. Increases in density of NPY+ processes in the older infants are gradual so that between 7 and 13 months of age, NPY+ fibers appear to have achieved adultlike densities. These observations indicate that NPY+ fibers in area 17 of newborn rhesus monkeys undergo postnatal maturation which reaches a plateau around 4 months of age. After monocular visual deprivation from birth to 4 months of age, either by eyelid suture or by

  10. Isolation and characterization of liver epithelial progenitor cells from normal adult rhesus monkeys (Macaca mulatta)

    Institute of Scientific and Technical Information of China (English)

    Lifang Jin; Shaohui Ji; Xianghui Tang; Xiangyu Guo; Yongqing Lu; Hongwei Chen; Hongkui Deng; Qi Zhou; Weizhi Ji

    2009-01-01

    @@ Dear Editor, Based on their ability to proliferate and the capacity to differentiate into specific cell types, hepatic progenitor/stem cells (HPCs) from adult human liver may have potential therapeutic effects on end-stage liver failure. In addition, adult HPCs have a reduced risk of teratoma formation and are not subject to the same ethical issues as fetal HPCs or embryonic stem cells [1]. The HPCs from rhesus monkeys are relevant because they may serve as a valuable preclinical model for assessment of cell therapy in humans. To date, there are no reports of HPCs or liver epithelial progenitor cells (LEPCs) isolated from normal adult rhesus monkey although a few studies in other species were reported [2, 3]. We report here for the first time the successful isolation of rhesus monkey LEPCs (mLEPCs) from normal adult livers (n=12).

  11. Homogeneous antibodies in lethally irradiated and autologous bone marrow reconstituted Rhesus monkeys

    International Nuclear Information System (INIS)

    Ten Rhesus monkeys were lethally irradiated and reconstituted with autologous bone marrow. During the restoration period, the animals were immunized with DNP-Rhesus albumin and IgA1lambda-10S human paraprotein. One or more transient homogenous immunoglobulin components appeared in sera of all experimental monkeys. In four animals, these homogeneous immunoglobulins were shown to be specific antibodies against DNP-Rhesus albumin. They gradually became as heterogeneous as those in control monkeys which were immunized but not irradiated and transplanted. The onset of the specific antibody response after immunization was slightly delayed in the experimental group. On determining the time necessary to reach normalization of the overall immunoglobulin levels and the normal heterogeneity of the immunoglobulin spectrum, it was found to be more than 1 year in most of the animals. (author)

  12. Brain aging in humans, chimpanzees (Pan troglodytes), and rhesus macaques (Macaca mulatta): magnetic resonance imaging studies of macro- and microstructural changes

    OpenAIRE

    Chen, Xu; Errangi, Bhargav; Li, Longchuan; Glasser, Matthew F.; Westlye, Lars T.; Fjell, Anders M.; Walhovd, Kristine B; Hu, Xiaoping; Herndon, James G; Preuss, Todd M.; Rilling, James K.

    2013-01-01

    Among primates, humans are uniquely vulnerable to many age-related neurodegenerative disorders. We used structural and diffusion magnetic resonance imaging (MRI) to examine the brains of chimpanzees and rhesus monkeys across each species' adult lifespan, and compared these results with published findings in humans. As in humans, gray matter volume decreased with age in chimpanzees and rhesus monkeys. Also like humans, chimpanzees showed a trend for decreased white matter volume with age, but ...

  13. A novel melano-lysosome in the retinal epithelium of rhesus monkeys.

    Science.gov (United States)

    Gouras, Peter; Brown, Kristy; Ivert, Lena; Neuringer, Martha

    2011-12-01

    The large phagocytic load that confronts the retinal pigment epithelium (RPE) is thought to play a possible role in the pathogenesis of age related macular degeneration (AMD) that afflicts both humans and monkeys. Our knowledge of how RPE degrades phagosomes and other intra-cellular material by lysosomal action is still rudimentary. In this paper we examine organelles that play a role in this process, melanosome, lysosomes and phagosomes, in the RPE of young and old rhesus monkeys in order to better understand lysosomal autophagy and heterophagy in the RPE and its possible role in AMD. We used electron microscopy to detect and describe the characteristics of melanosomes and lysosome-like organelles in the macular RPE of rhesus monkeys (Macaca mulatta) that were 1, 6, 24, 24, 26 and 35 years of age. The measurements include the number, shape and size of these organelles located in the basal, middle and apical regions of RPE cells. Phaagosomes were also examined but not counted or measured for size or shape because of their rarity. Melanosomes were homogeneously dark with a circular or elliptical shape and decreased in number with age. Smaller melanosomes were more common at the basal side of the RPE. Among the small melanosomes, we found an organelle that was losing melanin in varying degrees; in some cases was nearly devoid of melanin. Because of the melanin loss, we considered this organelle to be a unique type of autophagic melano-lysosome, which we called a Type 1 lysosome. We found another organelle, more canonically lysosomal, which we called a Type 2 lysosome. This organelle was composed of a light matrix containing melanosomes in various stages of degradation. Type 2 lysosomes without melanosomes were rare. Type 2 lysosomes increased while Type 1 decreased in number with age. Phagosomes were rare in both young and old monkeys. They made close contact with Type 2 lysosomes which we considered responsible for their degradation. Melanosomes are being lost from

  14. Dietary Omega-3 Fatty Acid Deficiency and Visual Loss in Infant Rhesus Monkeys

    OpenAIRE

    Neuringer, M.; Connor, W.E.; Van Petten, C; Barstad, L

    1984-01-01

    Linolenic acid (18:3 omega 3) is a dietary precursor of docosahexaenoic acid (22:6 omega 3), the major fatty acid in the photoreceptor membranes of the retina. We hypothesized that rhesus monkeys deprived of dietary omega-3 fatty acids during prenatal and postnatal development would show plasma depletion of these fatty acids and visual impairment. Semipurified diets low in omega-3 fatty acids were fed to one group of adult female rhesus monkeys throughout pregnancy and to their infants from b...

  15. Analysis of maternal microchimerism in rhesus monkeys (Macaca mulatta) using real-time quantitative PCR amplification of MHC polymorphisms

    OpenAIRE

    Bakkour, Sonia; Baker, Chris AR; Tarantal, Alice F; Wen, Li; Busch, Michael P; Lee, Tzong-Hae; McCune, Joseph M

    2014-01-01

    Although pregnancy-associated microchimerism is known to exist in humans, its clinical significance remains unclear. Fetal microchimerism has been documented in rhesus monkeys, but the trafficking and persistence of maternal cells in the monkey fetus and infant have not been fully explored. To investigate the frequency of maternal microchimerism in the rhesus monkey (Macaca mulatta), a real-time polymerase chain reaction (PCR) strategy was developed and validated to target polymorphic major h...

  16. Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys.

    Science.gov (United States)

    Abbink, Peter; Larocca, Rafael A; De La Barrera, Rafael A; Bricault, Christine A; Moseley, Edward T; Boyd, Michael; Kirilova, Marinela; Li, Zhenfeng; Ng'ang'a, David; Nanayakkara, Ovini; Nityanandam, Ramya; Mercado, Noe B; Borducchi, Erica N; Agarwal, Arshi; Brinkman, Amanda L; Cabral, Crystal; Chandrashekar, Abishek; Giglio, Patricia B; Jetton, David; Jimenez, Jessica; Lee, Benjamin C; Mojta, Shanell; Molloy, Katherine; Shetty, Mayuri; Neubauer, George H; Stephenson, Kathryn E; Peron, Jean Pierre S; Zanotto, Paolo M de A; Misamore, Johnathan; Finneyfrock, Brad; Lewis, Mark G; Alter, Galit; Modjarrad, Kayvon; Jarman, Richard G; Eckels, Kenneth H; Michael, Nelson L; Thomas, Stephen J; Barouch, Dan H

    2016-09-01

    Zika virus (ZIKV) is responsible for a major ongoing epidemic in the Americas and has been causally associated with fetal microcephaly. The development of a safe and effective ZIKV vaccine is therefore an urgent global health priority. Here we demonstrate that three different vaccine platforms protect against ZIKV challenge in rhesus monkeys. A purified inactivated virus vaccine induced ZIKV-specific neutralizing antibodies and completely protected monkeys against ZIKV strains from both Brazil and Puerto Rico. Purified immunoglobulin from vaccinated monkeys also conferred passive protection in adoptive transfer studies. A plasmid DNA vaccine and a single-shot recombinant rhesus adenovirus serotype 52 vector vaccine, both expressing ZIKV premembrane and envelope, also elicited neutralizing antibodies and completely protected monkeys against ZIKV challenge. These data support the rapid clinical development of ZIKV vaccines for humans. PMID:27492477

  17. Tissue tropism of simian immunodeficiency virus in rhesus monkeys

    International Nuclear Information System (INIS)

    Simian immunodeficiency virus (SIV) is a T-lymphotropic lentivirus that is genetically, immunologically, and morphologically related to the human immunodeficiency viruses type 1 and 2 (HIV-1, HIV-2). In rhesus monkeys, SIV induces a progressively fatal immunodeficiency syndrome strikingly similar to human acquired immunodeficiency syndrome (AIDS). The tissue and cellular tropism of SIV was determined by immunocytochemistry and in situ hybridization using a 3.48 kilobase SIV envelope gene probe labeled with biotin, 35S, or 3H. Probes labeled with 35S nonspecifically bound to tissue eosinophils and produced poor signal resolution compared to tritium labeled probes. Biotin labeled probes did not detect SIV under similar hybridization conditions. Formalin-fixed, paraffin-embedded tissues produced strong hybridization signal with superior morphology compared to frozen tissues. Gastrointestinal, respiratory, and lymphoid tissues most frequently contained SIV RNA. The distribution of SIV did not correlate with sex, or viral inoculum, but was most extensive in animals with SIV induced granulomatous encephalitis. SIV was most frequently observed in lymphocytes and macrophages. In the brain focal granulomas were composed almost entirely of EBM11+, lysozyme+, macrophages which contained large amounts of SIV RNA and p27 core protein detected by the monoclonal antibody R1C7. Cells away from granulomas in the brain parenchyma and around blood vessels contained virus and were compatible with oligodendrocytes and astrocytes. Lymph nodes in follicular hyperplasia contained small numbers of SIV positive cells compatible with lymphocytes in the paracortex and mantle zones as well as in cells of the germinal center. Lymph nodes in various stages of follicular depletion with expanded paracortices contained large numbers of cells with SIV RNA in lymphocytes and macrophages

  18. Behavioral and hormonal effects of attachment object separation in surrogate-peer-reared and mother-reared infant rhesus monkeys.

    Science.gov (United States)

    Meyer, J S; Novak, M A; Bowman, R E; Harlow, H F

    1975-09-01

    Mother-reared and surrogate-peer-reared rhesus monkeys were separated from their respective attachment objects at 6 months of age and tested for the following 9 weeks to determine their home-cage behavior and their pituitary-adrenocortical responses to stress. Both groups displayed a strong immediate behavioral response to separation which was characterized by increased vocalization, increased locomotion, and decreased self-play. However, the surrogate-peer-reared infants showed a subsequent recovery in their levels of self-play whereas the mother-reared infants instead developed stereotypic behavior patterns such as repetitive pacing. The 2 groups displayed similar plasma cortisol responses to weekly sessions in an apparatus equipped with animated toy "monsters". Mother-reared but not surrogate-peer-reared subjects, however, also manifested elevated cortisol levels when an animal in an adjacent cage was captured and removed for stress testing. Mother-reared infant monkeys thus responded in a stronger and more prolonged manner to the loss of their attachment object than surrogate-peer-reared infants. These results suggest that infant rhesus monkeys form stronger attachments to monkey mothers than to inanimate surrogate mothers, a phenomenon which has not been as clearly demonstrated using other indices of attachment strength. PMID:817950

  19. Familial hypercholesterolemia in a rhesus monkey pedigree: molecular basis of low density lipoprotein receptor deficiency.

    OpenAIRE

    HUMMEL, M.; Li, Z G; Pfaffinger, D; Neven, L.; Scanu, A M

    1990-01-01

    We have recently identified a family of rhesus monkeys with members exhibiting a spontaneous hypercholesterolemia associated with a low density lipoprotein receptor (LDLR) deficiency. By using the polymerase chain reaction, we now show that the affected monkeys are heterozygous for a nonsense mutation in exon 6 of the LDLR gene. This mutation changes the sequence of the codon for amino acid 284 (tryptophan) from TGG to TAG, thereby generating a nonsense codon potentially resulting in a trunca...

  20. Study of treatment of congenital Toxoplasma gondii infection in rhesus monkeys with pyrimethamine and sulfadiazine.

    OpenAIRE

    1995-01-01

    The efficacy of the combination of pyrimethamine and sulfadiazine for the treatment of congenital Toxoplasma gondii infection in rhesus monkeys was studied. The dosage regimen for pyrimethamine and sulfadiazine was established by pharmacokinetic studies in two monkeys. Those studies showed that the distributions of both drugs followed a one-compartment model. The serum elimination half-lives were found to be 5.2 h for sulfadiazine and 44.4 h for pyrimethamine. Sulfadiazine reached a maximum c...

  1. Biological effects of 239PuO2 inhalation in the Rhesus monkey

    International Nuclear Information System (INIS)

    Rhesus monkeys were exposed to polydisperse, high-fired 239PuO2 aerosols and have been studied for 3 yr to determine the biological effects associated with this inhalation exposure. Initial lung burdens in 16 monkeys exposed to aerosols of 239PuO2 ranged from 7 to 1800 nCi. Two monkeys are serving as controls. The inhaled 239 PuO2 was retained with a long effective half-life in the lung with some translocation from the lung to the pulmonary lymph nodes. In animals exposed to high levels of 239PuO2, there was a depression in the number of lymphocytes in the peripheral blood. However, blood lymphocytes cultured at time periods up to 30 mo after inhalation showed no increase in chromosome aberration frequency. An animal with an estimated initial lung burden of 1000 nCi showed marked alterations in respiratory function. Only slight respiratory changes were detected in the other animals evaluated. To date, three monkeys have died, two of radiation pneumonitis and the third of gastric torsion. Comparing these data from Rhesus monkeys with those obtained from baboons and Beagle dogs indicate that Rhesus monkeys are similar to dogs in their early radiation response

  2. A draft map of rhesus monkey tissue proteome for biomedical research.

    Directory of Open Access Journals (Sweden)

    Jin-Gyun Lee

    Full Text Available Though the rhesus monkey is one of the most valuable non-human primate animal models for various human diseases because of its manageable size and genetic and proteomic similarities with humans, proteomic research using rhesus monkeys still remains challenging due to the lack of a complete protein sequence database and effective strategy. To investigate the most effective and high-throughput proteomic strategy, comparative data analysis was performed employing various protein databases and search engines. The UniProt databases of monkey, human, bovine, rat and mouse were used for the comparative analysis and also a universal database with all protein sequences from all available species was tested. At the same time, de novo sequencing was compared to the SEQUEST search algorithm to identify an optimal work flow for monkey proteomics. Employing the most effective strategy, proteomic profiling of monkey organs identified 3,481 proteins at 0.5% FDR from 9 male and 10 female tissues in an automated, high-throughput manner. Data are available via ProteomeXchange with identifier PXD001972. Based on the success of this alternative interpretation of MS data, the list of proteins identified from 12 organs of male and female subjects will benefit future rhesus monkey proteome research.

  3. Effect of space flight on cytokine production and other immunologic parameters of rhesus monkeys

    Science.gov (United States)

    Sonnenfeld, G.; Davis, S.; Taylor, G. R.; Mandel, A. D.; Konstantinova, I. V.; Lesnyak, A.; Fuchs, B. B.; Peres, C.; Tkackzuk, J.; Schmitt, D. A.

    1996-01-01

    During a recent flight of a Russian satellite (Cosmos #2229), initial experiments examining the effects of space flight on immunologic responses of rhesus monkeys were performed to gain insight into the effect of space flight on resistance to infection. Experiments were performed on tissue samples taken from the monkeys before and immediately after flight. Additional samples were obtained approximately 1 month after flight for a postflight restraint study. Two types of experiments were carried out throughout this study. The first experiment determined the ability of leukocytes to produce interleukin-1 and to express interleukin-2 receptors. The second experiment examined the responsiveness of rhesus bone marrow cells to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). Human reagents that cross-reacted with monkey tissue were utilized for the bulk of the studies. Results from both studies indicated that there were changes in immunologic function attributable to space flight. Interleukin-1 production and the expression of interleukin-2 receptors was decreased after space flight. Bone marrow cells from flight monkeys showed a significant decrease in their response to GM-CSF compared with the response of bone marrow cells from nonflight control monkeys. These results suggest that the rhesus monkey may be a useful surrogate for humans in future studies that examine the effect of space flight on immune response, particularly when conditions do not readily permit human study.

  4. Elasticity and stress relaxation of rhesus monkey (Macaca mulatta) vocal folds.

    Science.gov (United States)

    Riede, Tobias

    2010-09-01

    Fundamental frequency is an important perceptual parameter for acoustic communication in mammals. It is determined by vocal fold oscillation, which depends on the morphology and viscoelastic properties of the oscillating tissue. In this study, I tested if stress-strain and stress-relaxation behavior of rhesus monkey (Macaca mulatta) vocal folds allows the prediction of a species' natural fundamental frequency range across its entire vocal repertoire as well as of frequency contours within a single call type. In tensile tests, the load-strain and stress-relaxation behavior of rhesus monkey vocal folds and ventricular folds has been examined. Using the string model, predictions about the species' fundamental frequency range, individual variability, as well as the frequency contour of 'coo' calls were made. The low- and mid-frequency range (up to 2 kHz) of rhesus monkeys can be predicted relatively well with the string model. The discrepancy between predicted maximum fundamental frequency and what has been recorded in rhesus monkeys is currently ascribed to the difficulty in predicting the behavior of the lamina propria at very high strain. Histological sections of the vocal fold and different staining techniques identified collagen, elastin, hyaluronan and, surprisingly, fat cells as components of the lamina propria. The distribution of all four components is not uniform, suggesting that different aspects of the lamina propria are drawn into oscillation depending on vocal fold tension. A differentiated recruitment of tissue into oscillation could extend the frequency range specifically at the upper end of the frequency scale. PMID:20709920

  5. Late effects of therapeutic irradiation on coronary arteries in the rhesus monkey

    International Nuclear Information System (INIS)

    Lesions of the coronary arteries have been found in rhesus monkeys treated with radiation schedules as employed in patients with malignant tumors in the thoracic area. These findings in subhuman primates may indicate that human coronary arteries are susceptible to developing atherosclerosis-like lesions after therapeutic irradiation

  6. COMPARATIVE ANATOMY OF THE VITREOUS BODY IN RHESUS-MONKEYS AND MAN

    NARCIS (Netherlands)

    WORST, JGF; LOS, LI

    1992-01-01

    In the isolated unfixed vitreous body a structural organization can be visualized by slitlamp microscopy or by an ink-injection technique. We discuss the observations on human and rhesus monkey (Macaca mulatta) vitreous bodies using the ink-injection technique. Advantages and disadvantages of this m

  7. In Vitro Interleukin-1 and 2 Production and Interleukin 2 Receptor Expression in the Rhesus Monkey

    Science.gov (United States)

    Schmitt, Didier A.; Sonnenfeld, Gerald; Husson, David; Tkaczuk, Jean; Andre, Eric; Schaffar, Laurance

    1996-01-01

    Anti-human monoclonal antibodies were used to detect and quantify interleukins-1 and 2 and interleukin-2 receptor expression in peripheral blood mononuclear cells from a rhesus monkey. Interleukin-1 production could be induced by phorbol esters (PMA) and was potentiated by phytohemagglutinin (PHA). Interleukin-2 secretion could also be induced by the combination of PHA and PMA, but only weakly with PHA alone. Interleukin-2 receptor expression was present in a subpopulation of unstimulated lymphocytes and could be enhanced by PHA or PMA. These data show once again that the rhesus monkey immune system is cross-reactive with the human one and that rhesus macaque could be a good model to study interleukin therapy.

  8. Protective effect and the therapeutic index of indralin in juvenile rhesus monkeys

    International Nuclear Information System (INIS)

    The radioprotective effect of indralin in rhesus monkeys was examined over 60 d following gamma irradiation. Male and female rhesus macaques (Macaca mulatta) 2-3-years-old and weighing 2.1-3.5 kg were used. Animals were exposed to total-body gamma irradiation from 60Co at a dose of 6.8 Gy (lethal dose, 100% lethality over 30 days). Indralin (40-120 mg kg-1) was administered intramuscularly 5 min prior to radiation exposure. Indralin taken at a dose of 120 mg kg-1 protected five out of six monkeys (compared with the radiation control group, in which all 10 animals died). The average effective dose of indralin in the monkeys exposed to gamma irradiation for 30 min was equal to 77.3 (63.3-94.3) mg kg-1, and the maximum tolerated dose of indralin administered to monkeys was 800 mg kg-1. Indralin reduced radiation-induced injuries in macaques, thus resulting in a less severe course of acute radiation syndrome. Delayed and less pronounced manifestation of the haemorrhagic syndrome of the disease, and milder forms of both leukopenia and anaemia were also noted. The therapeutic index for indralin, expressed as the ratio of the maximum tolerated dose to the average effective dose, was equal to 10. Therefore, indralin has a significant radioprotective effect against radiation and has a high therapeutic index in rhesus monkeys. (author)

  9. Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans

    Energy Technology Data Exchange (ETDEWEB)

    Asgharian, Bahman; Price, Owen; McClellan, Gene; Corley, Rick; Einstein, Daniel R.; Jacob, Richard E.; Harkema, Jack; Carey, Stephan A.; Schelegle, Edward; Hyde, Dallas; Kimbell, Julia S.; Miller, Frederick J.

    2012-11-01

    The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 µm in size were examined for endotracheal and and up to 5 µm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Finally, future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model.

  10. Bioassay of circulating luteinizing hormone in the rhesus monkey: comparison with radioimmunoassay during physiological changes

    International Nuclear Information System (INIS)

    The concentration of biologically active LH in Rhesus monkey (Macaca mulatta) serum was measured by a highly sensitive bioassay based upon testosterone production by dispersed rat interstitial cells. The sensitivity of the in vitro bioassay was equal to or higher than that of radioimmunoassay, with detection limits of 0.1 mIU of human menopausal gonadotropin (hMG) or 10 ng of a Rhesus pituitary gonadotropin preparation (LER-1909-2). Parallel dose-response curves were obtained for hMG and Rhesus monkey pituitary gonadotropin. The method permits bioassay of LH in 20--100 μl of serum from adult male monkeys, and from female monkeys during the follicular and luteal phases of the menstrual cycle. Bioactive LH concentrations could be assayed in 0.25 to 5 μl of serum from mid-cycle, postmenopausal, and castrated female monkeys. Serum LH was undetectable in two hypophysectomized adult female monkeys and six intact immature animals, and was 13 +- 6 (SD) mIU/ml in adult male monkeys. In adult females, follicular phase LH levels ranged from 17 to 169 mIU/ml, with a mean of 76 +- 52 mIU/ml. The midcycle LH peak was 1738 +- 742 mIU/ml and the luteal phase values ranged from 6-47 mIU/ml, with a mean of 35 +- 5 mIU/ml. Serum LH concentrations ranged from 100 to 900 mIU/ml in two menopausal females, and from 590--1480 mIU/ml in castrated females. Treatment of castrated female monkeys with estrogen plus progesterone produced an initial two-fold rise in sepum LH within 3 days, followed by a gradual decline to one-fourth to one-tenth of the initial levels after 10 days of treatment. Serum LH was suppressed to undetectable levels during the third week, and remained so for the duration of the 60-day treatment period

  11. Percutaneous transhepatic portal catheterization guided by ultrasound technology for islet transplantation in rhesus monkey

    Institute of Scientific and Technical Information of China (English)

    FengGao; Shao-DongAi; ShengLiu; Wen-BinZeng; WeiWang

    2012-01-01

    BACKGROUND: Pig islet xenotransplantation has the potential to overcome the shortage of donated human islets for islet cell transplantation in type 1 diabetes. Testing in non-human primate models is necessary before clinical application in humans. Intraportal islet transplantation in monkeys is usually performed by surgical infusion during laparotomy or laparoscopy. In this paper, we describe a new method of percutaneous transhepatic portal catheterization (PTPC) as an alternative to current methods of islet transplantation in rhesus monkeys. METHODS: We performed ultrasound-guided PTPC in five adult rhesus monkeys weighing 7-8 kg, with portal vein catheterization confirmed by digital subtraction angiography. We monitored for complications in the thoracic and abdominal cavity. To evaluate the safety of ultrasound-guided PTPC, we recorded the changes in portal pressure throughout the microbead transplantation procedure. RESULTS:  Ultrasound-guided PTPC and infusion of 16 000 microbeads/kg body weight into the portal vein was successful in all five monkeys. Differences in the hepatobiliary anatomy of rhesus monkeys compared to humans led to a higher initial complication rate. The first monkey died of abdominal hemorrhage 10 hours post-transplantation. The second suffered from a mild pneumothorax but recovered fully after taking only conservative measures. After gaining experience with the first two monkeys, we decreased both the hepatic puncture time and the number of puncture attempts required, with the remaining three monkeys experiencing no complications. Portal pressures initially increased proportional to the number of transplanted microbeads but returned to pre-infusion levels at 30 minutes post-transplantation. The changes in portal pressures occurring during the procedure were not significantly different. CONCLUSIONS: Ultrasound-guided PTPC is an effective, convenient, and minimally invasive method suitable for use in non-human primate models of

  12. Longevity studies in rhesus monkeys after X-ray and neutron irradiation with special emphasis on tumour induction

    International Nuclear Information System (INIS)

    Over the past 15 years experiments have been performed on the mortality of rhesus monkeys and the effects of bone marrow transplantation after irradiation with X-rays and fission neutrons. It had been previously established that, for neutrons as well as for X-rays, bone marrow transplantation was effective in protecting the animals from death due to the haemopoietic syndrome. Of the group of X-irradiated monkeys, 14 survived more than three years after irradiation, whereas in the neutron-irradiated group nine animals were long-term survivors. A control group of comparable age distribution comprises a total number of 13 non-treated rhesus monkeys. All animals are kept under continuous observation to study the late effects of radiation. After latent periods of 4 to 12 years, five neutron-irradiated and one X-irradiated animal died with tumours. The relation between the latency period, the radiation dose and the types and localizaton of tumours are discussed. The present results suggest relatively high effectiveness of fission neutrons for tumour induction. (author)

  13. Effects of the menstrual cycle on looking preferences for faces in female rhesus monkeys.

    Science.gov (United States)

    Lacreuse, Agnès; Martin-Malivel, Julie; Lange, Henry S; Herndon, James G

    2007-04-01

    Fluctuations of ovarian hormones across the menstrual cycle influence a variety of social and cognitive behaviors in primates. For example, female rhesus monkeys exhibit heightened interest for males and increased agonistic interactions with other females during periods of high estrogen levels. In the present study, we hypothesized that females' preference for males during periods of high estrogen levels is also expressed at the level of face perception. We tested four intact females on two face-tasks involving neutral portraits of male and female rhesus monkeys, chimpanzees and humans. In the visual preference task (VP), monkeys had to touch a button to view a face image. The image remained on the screen as long as the button was touched, and the duration of pressing was taken as an index of the monkey's looking time for the face stimulus. In the Face-Delayed Recognition Span Test (Face-DRST), monkeys were rewarded for touching the new face in an increasing number of serially presented faces. Monkeys were tested 5 days a week across one menstrual cycle. Blood was collected every other day for analysis of estradiol and progesterone. Two of the four females were cycling at the time of testing. We did not find an influence of the cycle on Face-DRST, likely due to a floor effect. In the VP however, the two cycling individuals looked longer at conspecific male faces than female faces during the peri-ovulatory period of the cycle. Such effects were absent for human and chimpanzee faces and for the two noncycling subjects. These data suggest that ovarian hormones may influence females' preferences for specific faces, with heightened preference for male faces during the peri-ovulatory period of the cycle. Heightened interest for stimuli of significant reproductive relevance during periods of high conception risk may help guide social and sexual behavior in the rhesus monkey. PMID:16909232

  14. Normative Values of Retinal Oxygen Saturation in Rhesus Monkeys: The Beijing Intracranial and Intraocular Pressure (iCOP) Study

    OpenAIRE

    Jing LI; Yang, Yiquan; Yang, Diya; Liu, Xiangxiang; Sun, Yunxiao; Wei, Shifei; Wang, Ningli

    2016-01-01

    Objective To study the normal values of the retinal oxygen saturation in Rhesus monkeys and to evaluated repeatability and reproducibility of retinal oxygen saturation measurements. Methods Eighteen adult Rhesus macaque monkeys were included in this experimental study. An Oxymap T1 retinal oximeter (Oxymap, Reykjavik, Iceland) was used to perform oximetry on all subjects. Global arterial (SaO2) and venous oxygen saturation (SvO2), arteriovenous difference in SO2 were measured. In the first ex...

  15. Effects of prenatal androgens on rhesus monkeys: A model system to explore the organizational hypothesis in primates

    OpenAIRE

    Thornton, Jan; Zehr, Julia L.; Loose, Michael D.

    2009-01-01

    After proposing the organizational hypothesis from research in prenatally androgenized guinea pigs (Phoenix et al., 1959), the same authors almost immediately extended the hypothesis to a nonhuman primate model, the rhesus monkey. Studies over the last 50 years have verified that prenatal androgens have permanent effects in rhesus monkeys on the neural circuits that underlie sexually dimorphic behaviors. These behaviors include both sexual and social behaviors, all of which are also influence...

  16. A Genetic System for Rhesus Monkey Rhadinovirus: Use of Recombinant Virus To Quantitate Antibody-Mediated Neutralization

    OpenAIRE

    Bilello, John P.; Morgan, Jennifer S.; Damania, Blossom; Lang, Sabine M.; Desrosiers, Ronald C.

    2006-01-01

    Rhesus monkey rhadinovirus (RRV), a simian gamma-2 herpesvirus closely related to the Kaposi sarcoma-associated herpesvirus, replicates lytically in cultured rhesus monkey fibroblasts and establishes persistence in B cells. Overlapping cosmid clones were generated that encompass the entire 130-kilobase-pair genome of RRV strain 26-95, including the terminal repeat regions required for its replication. Cloned RRV that was produced by cotransfection of overlapping cosmids spanning the entire RR...

  17. Comprehensive analysis of the T-cell receptor beta chain gene in rhesus monkey by high throughput sequencing

    OpenAIRE

    Li, Zhoufang; Liu, Guangjie; Tong, Yin; Zhang, Meng; Xu, Ying; Qin, Li; Wang, Zhanhui; Chen, Xiaoping; He, Jiankui

    2015-01-01

    Profiling immune repertoires by high throughput sequencing enhances our understanding of immune system complexity and immune-related diseases in humans. Previously, cloning and Sanger sequencing identified limited numbers of T cell receptor (TCR) nucleotide sequences in rhesus monkeys, thus their full immune repertoire is unknown. We applied multiplex PCR and Illumina high throughput sequencing to study the TCRβ of rhesus monkeys. We identified 1.26 million TCRβ sequences corresponding to 643...

  18. Auditory Rehabilitation in Rhesus Macaque Monkeys (Macaca mulatta) with Auditory Brainstem Implants

    Institute of Scientific and Technical Information of China (English)

    Zhen-Min Wang; Zhi-Jun Yang; Fu Zhao; Bo Wang; Xing-Chao Wang; Pei-Ran Qu; Pi-Nan Liu

    2015-01-01

    Background:The auditory brainstem implants (ABIs) have been used to treat deafness for patients with neurofibromatosis Type 2 and nontumor patients.The lack of an appropriate animal model has limited the study of improving hearing rehabilitation by the device.This study aimed to establish an animal model of ABI in adult rhesus macaque monkey (Macaca mulatta).Methods:Six adult rhesus macaque monkeys (M.mulatta) were included.Under general anesthesia,a multichannel ABI was implanted into the lateral recess of the fourth ventricle through the modified suboccipital-retrosigmoid (RS) approach.The electrical auditory brainstem response (EABR) waves were tested to ensure the optimal implant site.After the operation,the EABR and computed tomography (CT) were used to test and verify the effectiveness via electrophysiology and anatomy,respectively.The subjects underwent behavioral observation for 6 months,and the postoperative EABR was tested every two weeks from the 1st month after implant surgery.Result:The implant surgery lasted an average of 5.2 h,and no monkey died or sacrificed.The averaged latencies of peaks Ⅰ,Ⅱ and Ⅳ were 1.27,2.34 and 3.98 ms,respectively in the ABR.One-peak EABR wave was elicited in the operation,and one-or two-peak waves were elicited during the postoperative period.The EABR wave latencies appeared to be constant under different stimulus intensities;however,the amplitudes increased as the stimulus increased within a certain scope.Conclusions:It is feasible and safe to implant ABIs in rhesus macaque monkeys (M.mulatta) through a modified suboccipital RS approach,and EABR and CT are valid tools for animal model establishment.In addition,this model should be an appropriate animal model for the electrophysiological and behavioral study of rhesus macaque monkey with ABI.

  19. Relevance and clinical significance of serum resistin level in obese T2DM rhesus monkey models.

    Science.gov (United States)

    Qi, S-D; He, Z-L; Chen, Y; Ma, J; Yu, W-H; Li, Y-Y; Yang, F-M; Wang, J-B; Chen, L-X; Zhao, Y; Lu, S-Y

    2015-09-01

    Resistin is a type of hormone-like adipocytokines, which is secreted specifically by adipocytes. It may be a key factor in the development of type 2 diabetes mellitus (T2DM) from obesity- associated insulin resistance due to results that show that it has a close relationship with insulin resistance in rodents. We utilized the rhesus monkeys as study objects to preliminarily test the association with glucose metabolism and to conduct a correlation analysis for clinical parameters and serum resistin levels in obese rhesus monkey models of T2DM. The results suggested that resistin was significantly increased in T2DM monkeys (P negative correlation with islet β-cell function (HOMA-β). In the course of glucose metabolism, reverse release change of resistin and insulin in T2DM monkeys occurred, but the phenomenon that was not observed in the control group, these findings indicated that resistin negatively regulated and interfered with carbohydrate metabolism in T2DM monkey models. The character of the releasing change of resistin might be a unique process in T2DM. Therefore, all of the results could provide references for clinical diagnostic criteria for human cases of T2DM, and could have clinical significance for obese T2DM diagnosis and degree of insulin resistance. PMID:26069076

  20. Immunization with purified protein antigens from Streptococcus mutans against dental caries in rhesus monkeys.

    OpenAIRE

    Lehner, T; Russell, M W; Caldwell, J.; Smith, R.

    1981-01-01

    Protein antigens I, I/II, II, and III were prepared from Streptococcus mutans (serotype c). Their immunogenicities and protective effects against dental caries were investigated in 40 rhesus monkeys kept entirely on a human-type diet, containing about 15% sucrose. Antigens I, I/II and, to a lesser extent, antigen II induced significant reductions in dental caries, as compared with sham-immunized monkeys. This was achieved with 1 or 2 doses of antigen, the first of which was administered with ...

  1. Slow negative evoked potentials in the rhesus monkey (Macaca mulatta): myogenic versus neurogenic influences.

    Science.gov (United States)

    Fria, T J; Saad, M M; Doyle, W J; Cantekin, E I

    1984-02-01

    The influence of myogenic activity on the generation of slow negative evoked potentials (SN10) to octave, toneburst stimuli (0.5-2 Hz) was investigated in 5 rhesus monkeys (M. mulatta) by comparing responses obtained prior to and during total paralysis induced with curare. The SN10 could be easily elicited during paralysis, regardless of stimulus intensity, rate, or frequency. During paralysis, there were no systematic changes in either response latency or amplitude; variability in latency was less than 10% and changes in response amplitude were within 30%. These findings suggest that the myogenic contribution to the SN10 response is negligible and that this response is of neurogenic origin in the rhesus monkey. PMID:6198169

  2. Perceived control in rhesus monkeys (Macaca mulatta) - Enhanced video-task performance

    Science.gov (United States)

    Washburn, David A.; Hopkins, William D.; Rumbaugh, Duane M.

    1991-01-01

    This investigation was designed to determine whether perceived control effects found in humans extend to rhesus monkeys (Macaca mulatta) tested in a video-task format, using a computer-generated menu program, SELECT. Choosing one of the options in SELECT resulted in presentation of five trials of a corresponding task and subsequent return to the menu. In Experiments 1-3, the animals exhibited stable, meaningful response patterns in this task (i.e., they made choices). In Experiment 4, performance on tasks that were selected by the animals significantly exceeded performance on identical tasks when assigned by the experimenter under comparable conditions (e.g., time of day, order, variety). The reliable and significant advantage for performance on selected tasks, typically found in humans, suggests that rhesus monkeys were able to perceive the availability of choices.

  3. Tissue Distribution of Memory T and B Cells in Rhesus Monkeys following Influenza A Infection

    OpenAIRE

    Pichyangkul, Sathit; Yongvanitchit, Kosol; Limsalakpetch, Amporn; Kum-Arb, Utaiwan; Im-Erbsin, Rawiwan; Boonnak, Kobporn; Thitithayanont, Arunee; Jongkaewwattana, Anan; Wiboon-ut, Suwimon; Mongkolsirichaikul, Duangrat; Mahanonda, Rangsini; Spring, Michele; Chuang, Ilin; Mason, Carl J; Saunders, David L.

    2015-01-01

    Studies of influenza-specific immune responses in humans have largely assessed systemic responses involving serum Ab and peripheral blood T cell responses. However, recent evidence indicates that tissue-resident memory T (TRM) cells play an important role in local murine intrapulmonary immunity. Rhesus monkeys were pulmonary exposed to 2009 pandemic H1N1 virus at days 0 and 28 and immune responses in different tissue compartments were measured. All animals were asymptomatic postinfection. Alt...

  4. Elasticity and stress relaxation of rhesus monkey (Macaca mulatta) vocal folds

    OpenAIRE

    Riede, Tobias

    2010-01-01

    Fundamental frequency is an important perceptual parameter for acoustic communication in mammals. It is determined by vocal fold oscillation, which depends on the morphology and viscoelastic properties of the oscillating tissue. In this study, I tested if stress–strain and stress–relaxation behavior of rhesus monkey (Macaca mulatta) vocal folds allows the prediction of a species' natural fundamental frequency range across its entire vocal repertoire as well as of frequency contours within a s...

  5. Acute Brain Metabolic Effects of Cocaine in Rhesus Monkeys with a History of Cocaine Use

    OpenAIRE

    Henry, Porche’Kirkland; Murnane, Kevin; Votaw, John R.; Howell, Leonard L.

    2010-01-01

    Cocaine addiction involves an escalation in drug intake which alters many brain functions. The present study documented cocaine-induced changes in brain metabolic activity as a function of cocaine self-administration history. Experimentally naive rhesus monkeys (N=6) were given increasing access to cocaine under a fixed-ratio schedule of i.v. drug self-administration. PET imaging with F-18 labeled fluorodeoxyglucose (FDG) was used to measure acute i.m. cocaine-induced changes in brain metabol...

  6. Personality Structure in Brown Capuchin Monkeys: Comparisons with Chimpanzees, Orangutans, and Rhesus Macaques

    OpenAIRE

    Morton, F. Blake; Phyllis C Lee; Buchanan-Smith, Hannah M.; Brosnan, Sarah F.; Thierry, Bernard; Paukner, Annika; Frans B M de Waal; Widness, Jane; Essler, Jennifer L.; Weiss, Alexander

    2013-01-01

    Species comparisons of personality structure (i.e. how many personality dimensions and the characteristics of those dimensions) can facilitate questions about the adaptive function of personality in nonhuman primates. Here we investigate personality structure in the brown capuchin monkey (Sapajus apella), a New World primate species, and compare this structure to those of chimpanzees (Pan troglodytes), orangutans (Pongo spp.), and rhesus macaques (Macaca mulatta). Brown capuchins evolved beha...

  7. A simple model of radial nerve injury in the rhesus monkey to evaluate peripheral nerve repair

    OpenAIRE

    Wang, Dong; Huang, Xijun; Fu, Guo; Gu, Liqiang; Liu, Xiaolin; WANG, HONGGANG; Hu, Jun; Yi, Jianhua; Niu, Xiaofeng; Zhu, Qingtang

    2014-01-01

    Current research on bone marrow stem cell transplantation and autologous or xenogenic nerve transplantation for peripheral nerve regeneration has mainly focused on the repair of peripheral nerve defects in rodents. In this study, we established a standardized experimental model of radial nerve defects in primates and evaluated the effect of repair on peripheral nerve injury. We repaired 2.5-cm lesions in the radial nerve of rhesus monkeys by transplantation of autografts, acellular allografts...

  8. Severe dopaminergic neuron loss in rhesus monkey brain impairs morphine-induced conditioned place preference

    OpenAIRE

    Yan, Ting; Rizak, Joshua Dominic; Wang, Jianhong; Yang, Shangchuan; Ma, Yuanye; Hu, Xintian

    2015-01-01

    It is well known that dopamine (DA) is critical for reward, but the precise role of DA in reward remains uncertain. The aim of this study was to determine what percentage of dopaminergic neurons in the primate brain is required for the expression of conditioned reward by measuring the performance of DA-deficient rhesus monkeys in a morphine-induced conditioned place preference (CPP) paradigm. Animals with mild Parkinsonian symptoms successfully developed and retained a morphine preference tha...

  9. Severe dopaminergic neuron loss in rhesus monkey brain impairs morphine-induced conditioned place preference

    OpenAIRE

    Ting Yan; Yuanye Ma

    2015-01-01

    It is well known that dopamine is critical for reward, but the precise role of dopamine in reward remains uncertain. The aim of this study was to determine what percentage of dopaminergic neurons in the primate brain is required for the expression of conditioned reward by measuring the performance of dopamine-deficient rhesus monkeys in a morphine-induced conditioned place preference paradigm. Animals with mild Parkinsonian symptoms successfully developed and retained a morphine preference th...

  10. Plasmodium coatneyi-infected rhesus monkeys: a primate modelfor human cerebral malaria

    OpenAIRE

    Masamichi Aikawa; Brown, Arthur E.; C. Dahlem Smith; Tatsuya Tegoshi; Russell J. Howard; Thomas H. Hasler; Yoshihiro Ito; William E. Colins; H. Kyle Webster

    1992-01-01

    Although several animal models for human cerebral malaria have been proposed in the past, name have shown pathological findings that are similar to those seen in humans. In order to develop an animal model for human cerebral malaria, we studied the pathology of brains of Plasmodium coatneyi (primate malaria parasite)-infected rhesus monkeys. Our study demonstrated parazitized erythrocyte (PRBC) sequestration and cytoadherence of knobs on PRBC to endothelial cells in cerebral microvessels of t...

  11. Depressive-Like Behavioral Response of Adult Male Rhesus Monkeys during Routine Animal Husbandry Procedure

    OpenAIRE

    Hennessy, Michael B.; Brenda McCowan

    2014-01-01

    Social isolation is a major risk factor for the development of depressive illness; yet, no practical nonhuman primate model is available for studying processes involved in this effect. In a first study, we noted that adult male rhesus monkeys housed individually indoors occasionally exhibited a hunched, depressive-like posture. Therefore, Study 2 investigated the occurrence of a hunched posture by adult males brought from outdoor social groups to indoor individual housing. We also scored two ...

  12. Longitudinal Stability of Friendships in Rhesus Monkeys (Macaca mulatta): Individual- and Relationship-level Effects

    OpenAIRE

    Weinstein, Tamara A. R.; Capitanio, John P.

    2012-01-01

    The longevity of children’s friendships is influenced by a multitude of individual- and relationship-level attributes, but little is known about the factors that impact friendship maintenance in nonhuman primate juveniles. We investigated whether the following predicted the longitudinal stability of friendships in juvenile rhesus monkeys (Macaca mulatta): (a) individual characteristics including sex, dominance rank, matriline size, and temperament; and (b) relationship characteristics includi...

  13. Interaction Between Behavioral and Pharmacological Treatment Strategies to Decrease Cocaine Choice in Rhesus Monkeys

    OpenAIRE

    Banks, Matthew L.; Blough, Bruce E.; S. Stevens Negus

    2012-01-01

    Behavioral and pharmacotherapeutic approaches constitute two prominent strategies for treating cocaine dependence. This study investigated interactions between behavioral and pharmacological strategies in a preclinical model of cocaine vs food choice. Six rhesus monkeys, implanted with a chronic indwelling double-lumen venous catheter, initially responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and cocaine injections (0–0.1 mg/kg/injection, FR...

  14. Rhesus monkey lens as an in vitro model for studying oxidative stress

    International Nuclear Information System (INIS)

    Lenses from young rhesus monkeys were incubated in the presence of H2O2 or oxygen radical generating systems to determine their suitability as a model for investigating lenticular oxidative stress. Additionally, direct comparisons were made between the effects found with the monkey lenses and those observed with cultured rat lenses exposed to the same oxidizing systems. As in earlier studies with rat lenses the monkey lenses exhibited impaired ability to actively accumulate from the medium radioactively labelled rubidium and choline following exposure to oxidative stress. Based on the effects of various scavengers of oxygen radicals it appeared that the mechanisms responsible for lens damage were the same for both rat and monkey lenses. However, rat lenses were damaged by lower concentrations of oxidants than were monkey lenses. It was concluded that oxidative stress affects both rat and monkey lenses by similar mechanisms but that lenses from monkeys, and probably other primates, are more resistant to these effects because they have better endogenous antioxidant defenses

  15. Enhanced fecal elimination of stored hexachlorobenzene from rats and rhesus monkeys by hexadecane or mineral oil.

    Science.gov (United States)

    Rozman, K; Rozman, T; Greim, H

    1981-01-01

    The effect of various dietary treatments on the fecal excretion of [14C]-hexachlorobenzene (HCB) was studied in rats and rhesus monkeys. Cholestyramine and sesame oil failed to influence fecal excretion of HCB and/or metabolites. However, dietary administration of n-hexadecane (5%) increased fecal excretion of radioactivity 4-13-fold in rats and rhesus monkeys. Similarly, mineral oil in the diet (5%) of rhesus monkeys elicited a 6-9-fold increase in fecal excretion of HCB and/or metabolites. As a result of the mineral oil treatment, and enhanced depletion of HCB from blood and also of the stored HCB from adipose tissue was observed. The concentration of HCB in the blood declined in accordance with decreasing storage levels of HCB in adipose tissue. The major site of elimination of HCB and/or metabolites seemed to be the intestine; in particular, the cecum and the colon ascendens. Both hexadecane and mineral oil appeared to stimulate specifically this elimination path way. PMID:7336436

  16. Ordinal judgments of symbolic stimuli by capuchin monkeys (Cebus apella) and rhesus monkeys (Macaca mulatta): the effects of differential and nondifferential reward.

    Science.gov (United States)

    Beran, Michael J; Harris, Emily H; Evans, Theodore A; Klein, Emily D; Chan, Betty; Flemming, Timothy M; Washburn, David A

    2008-02-01

    Ordinal learning was investigated in capuchin monkeys (Cebus apella) and rhesus monkeys (Macaca mulatta). In Experiment 1, both species were presented with pairings of the Arabic numerals 0 to 9. Some monkeys were given food rewards equal to the value of the numeral selected and some were rewarded with a single pellet only for choosing the higher numeral within the pair. Both species learned to select the larger numeral, but only rhesus monkeys that were differentially rewarded performed above chance levels when presented with novel probe pairings. In Experiment 2, the monkeys were first presented with arrays of 5 familiar numerals (from the range 0 to 9) and then arrays of 5 novel letters (from the range A to J) with the same reward outcomes in place as in Experiment 1. Both species performed better with the numerals, suggesting that an ordinal sequence of all stimuli had been learned during Experiment 1, rather than a matrix of two-choice discriminations. PMID:18298281

  17. Clonidine attenuates morphine withdrawal and subsequent drug sensitization in rhesus monkeys1

    Institute of Scientific and Technical Information of China (English)

    Su-qing CHEN; Hai-feng ZHAI; Yan-ying CUI; Jie SHI; Bernard LE FOLL; Lin LU

    2007-01-01

    Aim: Clonidine is an α2 adrenoceptor agonist that is frequently used to reduce withdrawal symptoms during opioid detoxification in humans. The long-term effects of clonidine on withdrawal symptoms and its effects on subsequent drug exposure have not been thoroughly documented. The aim of the study was to determine if clonidine administered during morphine withdrawal in rhesus mon-keys produces long-lasting effects on withdrawal symptoms and alters the effects of subsequently taken drugs of abuse. Methods: Adult male rhesus monkeys were treated with increasing doses of morphine for 90 d to induce opiate (narcotic)dependence. The immediate and long-lasting effects of 1 week's administration of clonidine were measured via the recording of morphine withdrawal signs and the subsequent effects of challenge injections of morphine or cocaine. Results:Monkeys chronically treated with morphine displayed withdrawal signs that lasted 2 weeks after cessation of morphine administration and displayed sensitized re-sponses to subsequent morphine and cocaine injections. Clonidine significantly reduced certain morphine withdrawal signs and overall withdrawal score, but these effects did not persist upon cessation of clonidine treatment. Sensitization to the effects of morphine and cocaine were significantly reduced in monkeys previ-ously treated with clonidine. Conclusion: Our results suggest that in addition to its short-term alleviating effect on morphine withdrawal signs, clonidine may re-duce subsequent effects of drugs of abuse after prolonged abstinence.

  18. Elevation of blood lead concentration by continement in the rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Bushnell, P.J.; Shelton, S.E.; Bowman, R.E.

    1979-08-01

    Rhesus monkeys were exposed to lead (Pb) acetate under various regimens during the first 12 months of life. At 30 months of age, these animals and unexposed controls were confined to an unfamiliar experimental chamber for one week. Serum cortisol concentration and Pb concentration in whole blood (PbB) were measured prior to, during, and after this confinement. Cortisol concentrations rose 60 to 90% within 2 hours of confinement, and declined to baseline levels after 98 hours of confinement. Mean baseline PbB levels reflected the state of clearance of the previously-ingested lead, rose 25 to 35% within 2 hours of confinement, and reached mean maximum levels as much as 100% above baseline after 98 hours of confinement. The data are discussed in terms of hormonal mobilization of Pb stored in bone, and subgest: (1) that this storage is multicompartmental; (2) that more than one process is probably involved in its mobilization; (3) that cortisol probably does not directly affect PbB levels; and (4) stress should be considered a potential factor in determining the PbB in studies of Pb metabolism.

  19. Comparison of the transplacental pharmacokinetics of cortisol and triamcinolone acetonide in the rhesus monkey

    International Nuclear Information System (INIS)

    The late gestational age rhesus monkey was used to study the transplacental pharmacokinetics of radiolabeled triamcinolone acetonide (TAC) and cortisol. Tritiated-TAC and [14C]cortisol were administered simultaneously via the maternal radial vein were administered simultaneously via the maternal radial vein and blood samples were serially drawn from catheters implanted in both the maternal femoral artery and fetal umbilical vein and artery. High-performance liquid chromatography of the processed blood samples revealed that from 93 to 100% of the 3H in the fetal circulation was parent TAC, whereas only 14 to 49% of the 14C was cortisol during the 40-min period after dose administration. Fetal tissue samples taken at 3 hr after dose administration showed that 75 to 96% of the 3H present was TAC, whereas no cortisol was observed. TAC demonstrated dose-independent kinetics. Samples collected from the umbilical vein of the in situ placenta after fetectomy revealed that cortisol was extensively converted to cortisone by the placenta, whereas TAC was refractory to placental metabolism. This placental conversion of cortisol to cortisone and the further metabolism and conjugation of cortisol by the fetoplacental unit resulted in a fetal to maternal plasma cortisol ratio of 0.2. In contrast, the lack of placental or fetoplacental metabolism of TAC resulted in a fetal to maternal plasma TAC ratio of 0.6

  20. Prospective and Retrospective Metacognitive Abilities in Rhesus Monkeys

    Directory of Open Access Journals (Sweden)

    Jennifer Ding

    2007-06-01

    Full Text Available Metacognition refers to a knowledge of one’s own cognitive abilities and one’s aptitude to alter these abilities if necessary. Previous research from our lab shows that monkeys exhibit metacognitive abilities by accurately judging their own performance on perceptual and serial working memory tasks. The present study includes two phases during which a monkey makes retrospective and prospective judgments of confidence. In the retrospective phase of this experiment, the subject completes a recall task, and then judges his performance on the test phase by choosing from high and low-risk confidence choices. In the prospective task, the monkey makes his confidence judgment before the test, instead judging how well he learned during the study phase. An analysis of results indicates that monkeys can immediately transfer the ability to make metacognitive judgments from the serial working memory tasks in previous experiments to retrospective and prospective recall tasks in the present study. These findings underline the similarity between the non-human primate and human abilities to make confidence judgments. Further, they are the first evidence to date of a non-human primate making a prospective judgment of future performance, suggesting that the ability to use a metacognitive state to control one’s actions is not uniquely human.

  1. Incidence of cataracts in rhesus monkeys treated with whole-body irradiation

    International Nuclear Information System (INIS)

    The incidence of cataract formation was investigated in rhesus monkeys exposed to different doses of whole-body irradiation. Application of 850 to 900 rad (8.5 to 9 Gy) caused cataracts in 17% of the monkeys within 3 years after treatment; after 10 to 15 years, incidence increased to 100%. Young lenses showed a significantly lower incidence than adult lenses, although no differences in the stage of cataractogenesis could be demonstrated. Sex differences did not play a role in incidence and severity of cataracts. Lower doses (400 rad or 4 Gy) did not cause cataracts. In view of the close similarity between monkeys and humans, these results indicate that a single dose of 850 to 900 rad, sometimes employed in the treatment of acute myeloid leukemia in children, carries a strong risk of cataract development

  2. The calcium endocrine system of adolescent rhesus monkeys and controls before and after spaceflight

    Science.gov (United States)

    Arnaud, Sara B.; Navidi, Meena; Deftos, Leonard; Thierry-Palmer, Myrtle; Dotsenko, Rita; Bigbee, Allison; Grindeland, Richard E.

    2002-01-01

    The calcium endocrine system of nonhuman primates can be influenced by chairing for safety and the weightless environment of spaceflight. The serum of two rhesus monkeys flown on the Bion 11 mission was assayed pre- and postflight for vitamin D metabolites, parathyroid hormone, calcitonin, parameters of calcium homeostasis, cortisol, and indexes of renal function. Results were compared with the same measures from five monkeys before and after chairing for a flight simulation study. Concentrations of 1,25-dihydroxyvitamin D were 72% lower after the flight than before, and more than after chairing on the ground (57%, P system were similar to the effects of chairing on the ground, but were more pronounced. Reduced intestinal calcium absorption, losses in body weight, increases in cortisol, and higher postflight blood urea nitrogen were the changes in flight monkeys that distinguished them from the flight simulation study animals.

  3. The calcium endocrine system of adolescent rhesus monkeys and controls before and after spaceflight

    Science.gov (United States)

    Arnaud, Sara B.; Navidi, Meena; Deftos, Leonard; Thierry-Palmer, Myrtle; Dotsenko, Rita; Bigbee, Allison; Grindeland, Richard E.

    2002-01-01

    The calcium endocrine system of nonhuman primates can be influenced by chairing for safety and the weightless environment of spaceflight. The serum of two rhesus monkeys flown on the Bion 11 mission was assayed pre- and postflight for vitamin D metabolites, parathyroid hormone, calcitonin, parameters of calcium homeostasis, cortisol, and indexes of renal function. Results were compared with the same measures from five monkeys before and after chairing for a flight simulation study. Concentrations of 1,25-dihydroxyvitamin D were 72% lower after the flight than before, and more than after chairing on the ground (57%, P endocrine system were similar to the effects of chairing on the ground, but were more pronounced. Reduced intestinal calcium absorption, losses in body weight, increases in cortisol, and higher postflight blood urea nitrogen were the changes in flight monkeys that distinguished them from the flight simulation study animals.

  4. Profiling serum antibodies to Mycobacterium tuberculosis proteins in rhesus monkeys with nontuberculous Mycobacteria.

    Science.gov (United States)

    Min, Fangui; Pan, Jinchun; Wu, Ruike; Chen, Meiling; Kuang, Huiwen; Zhao, Weibo

    2016-02-14

    Recent evidence indicates that the prevalence of diseases caused by nontuberculous mycobacteria (NTM) has been increasing in both human and animals. In this study, antibody profiles of NTM in rhesus monkeys (Macaca mulatta) were determined and compared with those of monkeys infected with Mycobacterium tuberculosis complex (MTBC). Antibodies against 10 M. tuberculosis proteins, purified protein derivative (PPD), and mammalian old tuberculin (MOT) were detected in 14 monkeys naturally infected with NTM by indirect ELISA. Sera from 10 monkeys infected with MTBC and 10 healthy monkeys were set as controls. All antigens showed high serological reactivities to MTBC infections and low reactivities in healthy monkeys. NTM infections showed strong antibody responses to MOT and PPD; moderate antibody responses to 16kDa, U1, MPT64L, 14kDa, and TB16.3; and low antibody responses to 38kDa, Ag85b, CFP10, ESAT-6, and CFP10-ESAT-6. According to the criteria of MTBC, only CFP10, ESAT-6, and CFP10-ESAT-6 showed negative antibody responses in all NTM infections. Taken together, these results suggest that positive results of a PPD/MOT-based ELISA in combination with results of antibodies to M. tuberculosis-specific antigens, such as CFP10 and ESAT-6, could discriminate NTM and MTBC infections. Two positive results indicate an MTBC infection, and a negative result for an M. tuberculosis-specific antigen may preliminarily predict an NTM infection. PMID:26437786

  5. Severe dopaminergic neuron loss in rhesus monkey brain impairs morphine-induced conditioned place preference

    Directory of Open Access Journals (Sweden)

    Ting Yan

    2015-10-01

    Full Text Available It is well known that dopamine is critical for reward, but the precise role of dopamine in reward remains uncertain. The aim of this study was to determine what percentage of dopaminergic neurons in the primate brain is required for the expression of conditioned reward by measuring the performance of dopamine-deficient rhesus monkeys in a morphine-induced conditioned place preference paradigm. Animals with mild Parkinsonian symptoms successfully developed and retained a morphine preference that was equivalent to control monkeys. However, these monkeys could not maintain the preference as well as controls when they retained severe Parkinsonian symptoms. On the other hand, monkeys initially in a severe Parkinsonian state developed a preference for morphine, but this preference was weaker than that of the controls. Histological results showed that the loss of dopaminergic neurons in monkeys that had severe Parkinsonian symptoms was about 80% in comparison to the control monkeys. All these data suggest that a severely impaired dopamine system alters rewarding-seeking behavior in non-human primates.

  6. Morphine-induced conditioned place preference in rhesus monkeys: Resistance to inactivation of insula and extinction.

    Science.gov (United States)

    Wu, XuJun; Zhao, Ning; Bai, Fan; Li, ChuanYu; Liu, CiRong; Wei, JingKuan; Zong, Wei; Yang, LiXin; Ryabinin, Andrey E; Ma, YuanYe; Wang, JianHong

    2016-05-01

    Drug addicts experience strong craving episodes in response to drug-associated cues. Attenuating these responses using pharmacological or behavioral approaches could aid recovery from addiction. Cue-induced drug seeking can be modeled using the conditioned place preference procedure (CPP). Our previous work showed that conditioned place preference (CPP) can be induced by administration of increasing doses of morphine in rhesus monkeys. Here, we investigated whether expression of morphine-induced CPP can be attenuated by inhibiting activity of insular cortex or by repeated unreinforced exposures to the CPP test. The insula has been demonstrated to be involved in addiction to several drugs of abuse. To test its role in morphine CPP, bilateral cannulae were implanted into the insula in seven adult monkeys. The CPP was established using a biased apparatus by intramuscular injections of morphine at increasing doses (1.5, 3.0 and 4.5mg/kg) for each monkey. After the monkeys established morphine CPP, their insulae were reversibly inactivated by bilateral microinjection with 5% lidocaine (40μl) prior to the post-conditioning test (expression) of CPP using a within-subject design. The microinjections of lidocaine failed to affect CPP expression when compared to saline injections. We subsequently investigated morphine-associated memory during six episodes of CPP tests performed in these monkeys over the following 75.0±0.2months. While the preference score showed a declining trend with repeated testing, morphine-induced CPP was maintained even on the last test performed at 75months post-conditioning. This observation indicated strong resistance of morphine-induced memories to extinction in rhesus monkeys. Although these data do not confirm involvement of insula in morphine-induced CPP, our observation that drug-associated memories can be maintained over six drug-free years following initial experience with morphine has important implications for treatment of drug addiction

  7. Moderate Level Alcohol During Pregnancy, Prenatal Stress, or Both and Limbic-Hypothalamic-Pituitary-Adrenocortical Axis Response to Stress in Rhesus Monkeys

    Science.gov (United States)

    Schneider, Mary L.; Moore, Colleen F.; Kraemer, Gary W.

    2004-01-01

    This study examined the relationship between moderate-level prenatal alcohol exposure, prenatal stress, and postnatal response to a challenging event in 6-month-old rhesus monkeys. Forty-one rhesus monkey (Macaca mulatta) infants were exposed prenatally to moderate level alcohol, maternal stress, or both. Offspring plasma cortisol and…

  8. Cytogenetic and other biological effects of 239PuO2 inhaled by the rhesus monkey

    International Nuclear Information System (INIS)

    Sixteen immature rhesus monkeys were exposed via inhalation to an insoluble, polydisperse 239PuO2 aerosol labeled with 169Yb which had an activity median aerodynamic diameter of 1.6 μm and a sigma/sub g/ of 1.6. Four groups with three monkeys per group were exposed to achieve initial 239Pu lung burdens of 1000 to 2000, 200 to 300, 20 to 65, and 2 to 10 nCi, respectively. To determine early retention and distribution of the aerosol, four additional monkeys were exposed with initial lung burdens of 200 to 600 nCi and were sacrificed 4 hr and 30 days after inhalation exposure. Two monkeys were sham exposed and served as controls. Using data derived from external whole-body counting of the 169Yb label, it was estimated that the inhaled 239PuO2 was retained in the body with an average effective half-life of 1000 days with some translocation from the lung to the pulmonary lymph nodes. Chromosome aberrations were scored in blood lymphocytes cultured 1, 3, 7, 19, 31, and 43 months after inhalation. Only in animals with cumulative lung doses greater than 1000 rad was there a significant increase in the frequency of rings and dicentrics when compared to the controls. An animal with an estimated initial lung burden of 1000 nCi showed marked alterations in respiratory function 30 days prior to his death from pulmonary fibrosis 990 days after inhalation exposure. Only slight respiratory changes were detected in the other animals evaluated. To date, three monkeys have died, two with initial lung burdens of 1800 and 1000 nCi 239Pu which died from radiation pneumonitis and the third with an initial lung burden of 20 nCi which died of gastric torsion presumably not related to Pu exposure. Comparison of survival data from rhesus monkeys with those obtained from baboons and beagles indicates that rhesus monkeys, baboons, and dogs are similar in their early response to inhaled 239PuO2

  9. Novel Helicobacter species isolated from rhesus monkeys with chronic idiopathic colitis.

    Science.gov (United States)

    Fox, J G; Handt, L; Xu, S; Shen, Z; Dewhirst, F E; Paster, B J; Dangler, C A; Lodge, K; Motzel, S; Klein, H

    2001-05-01

    Chronic, idiopathic diffuse colitis is a well recognised clinical and pathological entity in captive rhesus monkeys. Six rhesus monkeys were diagnosed with clinically debilitating, chronic diarrhoea. Histologically, colonic tissues were characterised as chronic, moderate to severe colitis and typhlitis, with diffuse mononuclear inflammation of lamina propria, reactive lymphoid hyperplasia and multifocal micro-abscesses. Colonic tissues were cultured for Salmonella spp. and Shigella spp.; all results were negative. Samples were negative for Clostridium difficile A and B toxins, and special stains of colonic tissue for acid-fast bacteria were also negative. The six diarrhoeic monkeys tested gave negative results for serum IgG antibodies to herpes B virus, STLV, SRV and SIV. Colonic tissue from the six diarrhoeic and two clinically normal monkeys with histologically confirmed colitis from the same colony were also subjected to micro-aerobic culture. Micro-aerobic cultures from all eight monkeys incubated at 37 degrees C and 42 degrees C revealed pinpoint or spreading colonies on antibiotic-containing media. Bacteria were identified as gram-negative, oxidase positive and urease negative. Of the nine strains characterised biochemically, two separate biotypes (corresponding to different species by 16S rRNA analysis) were identified. One biotype (type 1), from non-diarrhoeic monkeys and the second biotype (type 2) from diarrhoeic animals with subclinical chronic colonic inflammation, differed by catalase activity, ability to reduce nitrate to nitrite and sensitivity to cephalothin. Complete 16S rRNA analysis of five of the nine strains characterised biochemically indicated that the organisms isolated were two novel Helicobacter spp. By electron microscopy, these novel helicobacters had spiral morphology with bipolar sheathed flagella. This is the first report describing the isolation of novel Helicobacter spp. from inflamed colons of rhesus monkeys. Studies are needed to

  10. Chronic high-frequency stimulation therapy in hemiparkinsonian rhesus monkeys using an implanted human DBS system.

    Science.gov (United States)

    Cao, Yiqun; Yin, Peihao; Hu, Xiaowu; Ge, Yiqin; Zhou, Xiaoping

    2013-05-01

    Deep brain stimulation (DBS) is routinely used in the treatment of Parkinson's disease, tremor disease, dystonia, and epilepsy. This study aims to establish a hemiparkinsonian monkey model and to investigate the effect of implanted human DBS system for the chronic alleviation of parkinsonian symptoms. Hemiparkinsonism was induced in four rhesus monkeys by unilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. DBS leads were implanted stereotaxically in the right subthalamic (STN) of the monkeys. Subcutaneous extension wires were used to connect the leads to the internal pulse generators (IPG) for stimulation in two of the monkeys (human DBS test group). Post-operative imaging studies confirmed optimal locations of lead contacts. One week later, the IPG was turned on to determine the optimal stimulating parameters, using apomorphine (APO)-induced rotation as a behavioral readout. Animal behavior was scored on a scale of 0-10 over a 12-month period using the modified disability rating scale of hemiparkinsonian monkeys (DRSH). Parkinsonian symptoms in the group of monkeys with DBS improved dramatically (DRSH 3-4) compared to controls (DRSH 7-8). DBS leads were within the STN without intracranial hemorrhage, infection, or other serious complications. Histological examination showed cell necrosis and lymphocytic infiltration of the tissues around the lead and STN gliosis surrounding the lead contact. This study demonstrates that therapeutically effective human DBS systems can be established in relevant disease models in monkeys. Such combination of human DBS systems in hemiparkinsonian monkeys should be valuable in studying the mechanism of action and chronic consequences of DBS therapy in humans. PMID:22622869

  11. The serotonin transporter in rhesus monkey brain: comparison of DASB and citalopram binding sites

    International Nuclear Information System (INIS)

    We have characterized the interaction of the serotonin transporter ligand [3H]-N,N-dimethyl-2-(2-amino-4-cyanophenylthio)-benzylamine (DASB) with rhesus monkey brain in vitro using tissue homogenate binding and autoradiographic mapping. [3H]-DASB, a tritiated version of the widely used [11C] positron emission tomography tracer, was found to selectively bind to a single population of sites with high affinity (K d=0.20±0.04 nM). The serotonin transporter density (B max) obtained for rhesus frontal cortex was found to be 66±8 fmol/mg protein using [3H]-DASB, similar to the B max value obtained using the reference radioligand [3H]-citalopram, a well-characterized and highly selective serotonin reuptake inhibitor (83±22 fmol/mg protein). Specific binding sites of both [3H]-DASB and [3H]-citalopram were similarly and nonuniformly distributed throughout the rhesus central nervous system, in a pattern consistent with serotonin transporter localization reported for human brain. Regional serotonin transporter densities, estimated from optical densities of the autoradiographic images, were well correlated between the two radioligands. Finally, DASB and fluoxetine showed dose-dependent full inhibition of [3H]-citalopram binding in a competition autoradiographic study, with K i values in close agreement with those obtained from rhesus brain homogenates. This side-by-side comparison of [3H]-DASB and [3H]-citalopram binding sites in rhesus tissue homogenates and in adjacent rhesus brain slices provides additional support for the use of [11C]-DASB to assess the availability and distribution of serotonin transporters in nonhuman primates

  12. The serotonin transporter in rhesus monkey brain: comparison of DASB and citalopram binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Zeng Zhizhen [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States)]. E-mail: zhizhen_zeng@merck.com; Chen, T.-B. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Miller, Patricia J. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Dean, Dennis [Labeled Compound Synthesis Group, Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065-0900 (United States); Tang, Y.S. [Labeled Compound Synthesis Group, Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065-0900 (United States); Sur, Cyrille [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Williams, David L. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States)

    2006-05-15

    We have characterized the interaction of the serotonin transporter ligand [{sup 3}H]-N,N-dimethyl-2-(2-amino-4-cyanophenylthio)-benzylamine (DASB) with rhesus monkey brain in vitro using tissue homogenate binding and autoradiographic mapping. [{sup 3}H]-DASB, a tritiated version of the widely used [{sup 11}C] positron emission tomography tracer, was found to selectively bind to a single population of sites with high affinity (K {sub d}=0.20{+-}0.04 nM). The serotonin transporter density (B {sub max}) obtained for rhesus frontal cortex was found to be 66{+-}8 fmol/mg protein using [{sup 3}H]-DASB, similar to the B {sub max} value obtained using the reference radioligand [{sup 3}H]-citalopram, a well-characterized and highly selective serotonin reuptake inhibitor (83{+-}22 fmol/mg protein). Specific binding sites of both [{sup 3}H]-DASB and [{sup 3}H]-citalopram were similarly and nonuniformly distributed throughout the rhesus central nervous system, in a pattern consistent with serotonin transporter localization reported for human brain. Regional serotonin transporter densities, estimated from optical densities of the autoradiographic images, were well correlated between the two radioligands. Finally, DASB and fluoxetine showed dose-dependent full inhibition of [{sup 3}H]-citalopram binding in a competition autoradiographic study, with K {sub i} values in close agreement with those obtained from rhesus brain homogenates. This side-by-side comparison of [{sup 3}H]-DASB and [{sup 3}H]-citalopram binding sites in rhesus tissue homogenates and in adjacent rhesus brain slices provides additional support for the use of [{sup 11}C]-DASB to assess the availability and distribution of serotonin transporters in nonhuman primates.

  13. Comparison of the chromosomal radiosensitivity of blood lymphocytes and stem-cell spermatogonia in the rhesus monkey and the mouse

    International Nuclear Information System (INIS)

    By experiments similar to those with the mouse we studied, in the rhesus monkey (Macaca mulatta), the induction by X-rays of reciprocal translocations in steam-cell spermatogonia and of dicentric chromosomes in blood lymphocytes. Human blood lymphocytes and rhesus monkey lymphocytes showed about equal sensitivity to dicentric induction. This equal radiosensitivity of somatic cells, however, provides no clue to the quantitative extrapolation to the human situation of the data obtained on translocation induction in stem-cell spermatogonia of the rhesus monkey. In our opinion, only direct observations on induced chromosomal aberrations in germ cells of higher primates and man can play a decisive role in estimating human genetic radiation risks arising from chromosomal aberrations. (orig./AJ)

  14. Investigations of rhesus monkey video-task performance: evidence for enrichment.

    Science.gov (United States)

    Washburn, D A; Rumbaugh, D M

    1992-09-01

    We have developed the Language Research Center's Computerized Test System (LRC-CTS) for psychological research. Basically, the LRC-CTS is a battery of software tasks--computerized versions of many of the classic testing paradigms of cognitive and comparative psychology--and the hardware required to administer them. An XT- or 386-compatible computer is connected to a color monitor, onto which computer-generated stimuli are presented. Sound feedback is delivered through an external speaker/amplifier, and a joystick is used as an input device. The animals reach through the mesh of their home cages to manipulate the joystick, which causes isomorphic movements of a cursor on the screen thereby allowing animals to respond according to the varied demands of the tasks. Correct responses are rewarded with a fruit-flavored chow pellet. Using this technology, we have trained and tested rhesus monkeys, a variety of apes, human adults, and normally developing or mentally retarded human children. Other labs using the LRC-CTS are beginning to report encouraging results with other monkey species as well. From this research, a number of interesting and important psychological findings have resulted. In the present paper, however, evidence will be reviewed which suggests that the LRC-CTS is an effective means of providing environmental enrichment to singly housed rhesus monkeys. PMID:11538195

  15. Interactive effects of morphine and dopaminergic compounds on spatial working memory in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    Jian-Hong Wang; Joshua Dominie Rizak; Yan-Mei Chen; Liang Li; Xin-Tian Hu; Yuan-Ye Ma

    2013-01-01

    Opiates and dopamine (DA) play key roles in learning and memory in humans and animals.Although interactions between these neurotransmitters have been found,their functional roles remain to be fully elucidated,and their dysfunction may contribute to human diseases and addiction.Here we investigated the interactions of morphine and dopaminergic neurotransmitter systems with respect to learning and memory in rhesus monkeys by using the Wisconsin General Test Apparatus (WGTA) delayed-response task.Morphine and DA agonists (SKF-38393,apomorphine and bromocriptine) or DA antagonists (SKF-83566,haloperidol and sulpiride) were co-administered to the monkeys 30 min prior to the task.We found that dose-patterned co-administration of morphine with D1 or D2 antagonists or agonists reversed the impaired spatial working memory induced by morphine or the compounds alone.For example,morphine at 0.01 mg/kg impaired spatial working memory,while morphine (0.01 mg/kg) and apomorphine (0.01 or 0.06 mg/kg) co-treatment ameliorated this effect.Our findings suggest that the interactions between morphine and dopaminergic compounds influence spatial working memory in rhesus monkeys.A better understanding of these interactive relationships may provide insights into human addiction.

  16. Reinforcing and discriminative stimulus effects of 1-benzylpiperazine and trifluoromethylphenylpiperazine in rhesus monkeys.

    Science.gov (United States)

    Fantegrossi, W E; Winger, G; Woods, J H; Woolverton, W L; Coop, A

    2005-02-14

    1-Benzylpiperazine (BZP) and 1-(3-trifluoromethylphenyl)piperazine (TFMPP) are two designer drugs that are often sold in combination tablets via the internet. The discriminative stimulus properties and reinforcing effects of these compounds have not previously been assessed in laboratory primates. In this regard, the reinforcing effects of BZP and TFMPP (alone, and in combination) were assessed via intravenous self-administration in rhesus monkeys previously trained to self-administer cocaine, while the discriminative stimulus effects of these compounds were determined in rhesus monkeys trained to discriminate amphetamine (AMPH) from saline. BZP was an effective reinforcer in self-administration tests, and appeared to induce long-lasting direct effects on behavior following sessions where BZP intakes were large. Additionally, BZP occasioned AMPH-appropriate responding in a dose-dependent manner, and produced full generalization in all monkeys tested. In contrast, TFMPP was not self-administered by any subjects and occasioned essentially no AMPH-appropriate responding at any dose tested. Non-contingent TFMPP administration had direct effects on behavior and abolished subsequent cocaine-maintained responding. Similarly, self-administration of various ratios of BZP:TFMPP combinations engendered less responding than did BZP alone. The present results suggest that BZP has abuse liability of the amphetamine type, but that such effects are not shared by TFMPP. PMID:15664717

  17. Investigations of rhesus monkey video-task performance: evidence for enrichment

    Science.gov (United States)

    Washburn, D. A.; Rumbaugh, D. M.

    1992-01-01

    We have developed the Language Research Center's Computerized Test System (LRC-CTS) for psychological research. Basically, the LRC-CTS is a battery of software tasks--computerized versions of many of the classic testing paradigms of cognitive and comparative psychology--and the hardware required to administer them. An XT- or 386-compatible computer is connected to a color monitor, onto which computer-generated stimuli are presented. Sound feedback is delivered through an external speaker/amplifier, and a joystick is used as an input device. The animals reach through the mesh of their home cages to manipulate the joystick, which causes isomorphic movements of a cursor on the screen thereby allowing animals to respond according to the varied demands of the tasks. Correct responses are rewarded with a fruit-flavored chow pellet. Using this technology, we have trained and tested rhesus monkeys, a variety of apes, human adults, and normally developing or mentally retarded human children. Other labs using the LRC-CTS are beginning to report encouraging results with other monkey species as well. From this research, a number of interesting and important psychological findings have resulted. In the present paper, however, evidence will be reviewed which suggests that the LRC-CTS is an effective means of providing environmental enrichment to singly housed rhesus monkeys.

  18. Food intake and meal patterns in rhesus monkeys: Significance of chronic hyperinsulinemia

    International Nuclear Information System (INIS)

    To investigate the role of plasma insulin on food intake, we have examined the effect of naturally occurring chronic hyperinsulinemia on the feeding behavior of male rhesus monkeys. Two groups of monkeys, a group with normal fasting insulin concentrations (52.4 +/- 2.2 microU/ml) (mean +/- SE) and a hyperinsulinemic group (148.6 +/- 14.5 microU/ml), were selected to be similar in weight, 13.0 +/- 1.0 and 15.3 +/- 0.5 kg, respectively, prior to study. Food intake and feeding patterns were recorded and analyzed. No differences in either daily caloric intake, 815.2 +/- 27.4 versus 890.0 +/- 64.2 kcal (p less than 0.32), or feeding patterns were found. The number of meals taken per day did not differ between the two groups, 8.7 +/- 1.7 versus 6.7 +/- 1.1 (p less than 0.35), nor did meal size differ, 129 +/- 16.5 versus 110.5 +/- 16.3 (p less than 0.45). We conclude that chronic endogenous hyperinsulinemia as it occurs naturally in some obese rhesus monkeys has no significant effect on daily feeding behavior

  19. Luteal phase defects in the rhesus monkey: the significance of serum FSH:LH ratios.

    Science.gov (United States)

    Wilks, J W; Hodgen, G D; Ross, G T

    1976-12-01

    Luteal phases of an abbreviated duration or suboptimal progesterone secretion were identified in the rhesus monkey. Characterization of menstrual cycles with short luteal phases (8 days) in 5 monkeys revealed the following deviations from normal: a. a failure of serum FSH to decline progressively from an early follicular phase high to a preovulatory nadir; b. a commonly inadequate, or absent, preovulatory FSH surge; c. subnormal serum LH concentrations during both the follicular and luteal portions of the menstrual cycle; d. ratios of serum FSH:LH which did not progressively decrease during the follicular phase; and e. serum estradiol concentrations below normal values during the luteal portion of the menstrual cycle. One monkey had abnormally low serum concentrations of progesterone, although the luteal phase was 19 days in duration. Serum gonadotropin and estradiol patterns in this latter monkey were identical to those observed in monkeys with short luteal phases. It is concluded that inappropriate ratios of serum FSH:LH during the follicular phase of the menstrual cycle result in impaired corpus leteum function. The data document the usefulness of the nonhuman primate for investigating those luteal phase defects which also occur in the woman. PMID:826543

  20. Metabolism of kadsurenone and 9,10-dihydrokadsurenone in rhesus monkeys and rat liver microsomes

    International Nuclear Information System (INIS)

    The metabolism of the PAF antagonists kadsurenone and tritium-labeled 9,10-dihydrokadsurenone was studied in rhesus monkeys and rat liver microsomes. The monkey metabolites of the two drugs were isolated as their glucuronide conjugates from the urine of iv dosed males. The metabolites from both monkey and microsomal metabolism were purified by reverse phase HPLC and identified by spectral (NMR, UV, and mass spectrometric) analysis. The principal pathway of biotransformation of the tritium-labeled 9,10-dihydrokadsurenone in monkeys was hydroxylation of the C-5 propyl side chain to give two metabolites, 10-hydroxy-9,10-dihydrokadsurenone and 9-hydroxy-9,10-dihydrokadsurenone. These compounds were excreted as glucuronides. Microsomal incubation of tritium-labeled 9,10-dihydrokadsurenone yielded the 10-, 9-, and 8-hydroxy-9,10-dihydrokadsurenone as major metabolites. Kadsurenone was also metabolized at the C-5 side chain, an allyl group. The monoglucuronide of 9,10-dihydroxykadsurenone was isolated from monkey urine. Spectral analysis was not definitive as to the site of conjugation, and the structure of the metabolite was assigned as the C-10 conjugate. A major metabolite of rat liver microsomal incubation of kadsurenone was 9,10-dihydroxykadsurenone

  1. Inhalation anesthetic-induced neuronal damage in the developing rhesus monkey.

    Science.gov (United States)

    Zou, Xiaoju; Liu, Fang; Zhang, Xuan; Patterson, Tucker A; Callicott, Ralph; Liu, Shuliang; Hanig, Joseph P; Paule, Merle G; Slikker, William; Wang, Cheng

    2011-01-01

    The combination of nitrous oxide gas (N(2)O) and isoflurane (ISO) vapor is commonly used in pediatric surgical procedures for human infants and children to produce unconsciousness and analgesia. Because of obvious limitations it is difficult to thoroughly explore the effects of pediatric anesthetic agents on neurons in human infants or children. Due to the complexity of the primate brain, the monkey is often the animal model of choice for developmental neurotoxicology experiments, and it is in the rhesus monkey that the phenomenon of interest (anesthetic-induced neuronal cell death in the brain) has been previously reported. Recent reports indicate that exposure of the developing brain to general anesthetics that block N-methyl-D-aspartate (NMDA)-type glutamate receptors or potentiate gamma-aminobutyric acid (GABA) receptors can trigger widespread apoptotic cell death in rodents. The present study was performed to determine whether prolonged exposure of developing nonhuman primates to a clinically relevant combination of nitrous oxide and isoflurane produces neuronal damage. Postnatal day (PND) 5-6 rhesus monkeys were exposed to N(2)O (70%) or ISO (1.0%) alone, or N(2)O plus ISO for 8 h. Inhalation of the combination of 70% N(2)O+1% ISO produces a surgical plane of anesthesia. Six hours after completion of anesthetic administration the monkeys were examined for neurotoxic effects. No significant neurotoxic effects were observed for the monkeys exposed to N(2)O or ISO alone. However, neuronal damage was apparent when N(2)O was combined with ISO as indicated by increased numbers of caspase-3-, Silver staining- and Fluoro-Jade C-positive cells in the frontal cortex, temporal gyrus and hippocampus. Electron micrographs indicated typical swelling of the cytoplasm and nuclear condensation in the frontal cortex. These data suggest that prolonged exposure to inhaled anesthetics (a combination of N(2)O and ISO) in the developing rhesus monkey results in neuronal damage, and

  2. Viewing preferences of rhesus monkeys related to memory for complex pictures, colours and faces.

    Science.gov (United States)

    Wilson, F A; Goldman-Rakic, P S

    1994-01-31

    In order to determine the preferences of rhesus monkeys for visual stimuli, their eye movements were measured in response to presentations of complex pictures, fields of uniform colour, and of faces using the scleral search coil technique. The monkeys (n = 4) controlled both the onset and offset of the stimuli by the direction of their gaze. Each stimulus was presented 4 times, with 0 or 2, and 36 or 38 trials between successive presentations. Several trends were apparent in their scanning behaviour: (1) all 4 monkeys spent more time looking at pictures and faces compared to colour fields. As individuals, they differed in their overall propensity in looking at visual stimuli: monkeys that spent the most (or least) time looking at pictures spent the most (or least) time looking at colour fields. (2) Although the monkeys appeared to prefer pictures and faces to colour fields as measured by gaze duration, preferences for individual pictures, faces and colour fields were not evident. (3) Memory for recently presented stimuli substantially affected gaze duration which was significantly longer for the first compared to the second presentation of the pictures and faces, and memory was estimated to influence gaze duration over as many as 38 intervening trials. These effects were not significant in the case of colour fields. (4) There were no significant differences either in the average latencies to initiate eye movements or the number of saccades on the first and second presentations of pictures, colors or faces for the 4 monkeys. However, the average latencies to the first eye movement within a trial were longer for colour fields than for pictures for all 4 monkeys. Individual monkeys differed substantially in their mean latencies for the initiation of the first eye movement within a trial, which ranged from 235 ms to 414 ms in the two extreme cases. (5) At the presentation of faces, the monkeys tended to make saccades to major facial features, and only occasionally to

  3. Tissue Distribution of Memory T and B Cells in Rhesus Monkeys following Influenza A Infection.

    Science.gov (United States)

    Pichyangkul, Sathit; Yongvanitchit, Kosol; Limsalakpetch, Amporn; Kum-Arb, Utaiwan; Im-Erbsin, Rawiwan; Boonnak, Kobporn; Thitithayanont, Arunee; Jongkaewwattana, Anan; Wiboon-ut, Suwimon; Mongkolsirichaikul, Duangrat; Mahanonda, Rangsini; Spring, Michele; Chuang, Ilin; Mason, Carl J; Saunders, David L

    2015-11-01

    Studies of influenza-specific immune responses in humans have largely assessed systemic responses involving serum Ab and peripheral blood T cell responses. However, recent evidence indicates that tissue-resident memory T (TRM) cells play an important role in local murine intrapulmonary immunity. Rhesus monkeys were pulmonary exposed to 2009 pandemic H1N1 virus at days 0 and 28 and immune responses in different tissue compartments were measured. All animals were asymptomatic postinfection. Although only minimal memory immune responses were detected in peripheral blood, a high frequency of influenza nucleoprotein-specific memory T cells was detected in the lung at the "contraction phase," 49-58 d after second virus inoculation. A substantial proportion of lung nucleoprotein-specific memory CD8(+) T cells expressed CD103 and CD69, phenotypic markers of TRM cells. Lung CD103(+) and CD103(-) memory CD8(+) T cells expressed similar levels of IFN-γ and IL-2. Unlike memory T cells, spontaneous Ab secreting cells and memory B cells specific to influenza hemagglutinin were primarily observed in the mediastinal lymph nodes. Little difference in systemic and local immune responses against influenza was observed between young adult (6-8 y) and old animals (18-28 y). Using a nonhuman primate model, we revealed substantial induction of local T and B cell responses following 2009 pandemic H1N1 infection. Our study identified a subset of influenza-specific lung memory T cells characterized as TRM cells in rhesus monkeys. The rhesus monkey model may be useful to explore the role of TRM cells in local tissue protective immunity after rechallenge and vaccination. PMID:26408671

  4. Selection of unrelated donors for bone marrow transplantation studied in rhesus monkeys

    International Nuclear Information System (INIS)

    Graft versus Host disease (GvHD) remains to be a severe limitation to a more general application of bone marrow transplantation. Clinically acceptable results are restricted to those potential recipients for which a major histocompatibility complex (MHC) identical sibling donor is available. At an average family size of 2 to 3 siblings, the frequency of such donors is not more than approximately 30%. This pre-clinical study in rhesus monkeys is directed at the selection of donors for recipients which lack an MHC identical sibling. (Auth.)

  5. Effect of total body irradiation on skeletal growth and cataract formation in rhesus monkey

    International Nuclear Information System (INIS)

    The effect of total body irradiation in single doses of 400-950 rad on skeletal growth and the development of lens cataract was investigated in 21 rhesus monkeys. The results suggest that exposure to irradiation before or during adolescent growth in children may lead to bone shortening when doses of 750 rad or higher are concerned, and that treatment of children with TBI in excess of 750 rad - as is sometimes employed in conjunction with bone marrow transplantation for the treatment of leukemia - may carry a strong risk for the subsequent development of cataract formation. (C.F.)

  6. Interactions between delta9-tetrahydrocannabinol and heroin: self-administration in rhesus monkeys

    OpenAIRE

    Li, Jun-Xu; Koek, Wouter; France, Charles P.

    2012-01-01

    The cannabinoid receptor agonist delta9-tetrahydrocannabinol (THC) enhances the antinociceptive effects of mu opioid receptor agonists, raising the possibility of using a combination of THC and opioids for treating pain. This study examined the effects of noncontingent and contingent administration of THC on i.v. heroin self-administration in rhesus monkeys. Self-administration of different unit doses of heroin (0.0001–0.1 mg/kg/infusion) generated a typical inverted U-shaped dose-response cu...

  7. Radioprotective effects of CBLB502 on γ-radiated Rhesus monkey

    OpenAIRE

    Shen, Xing; Guo-lin XIONG; Xie, Ling; Ling-ling GUO; Li, Ming; Zhao, Yan-Fang; Wang, Lei; Hong, Jian; Yang, Meng; Zhao, Li; Peng, Rui-Yun; Wang, Yong; Yang, Xiao-Ming; Qing-liang LUO; Zu-yin YU

    2015-01-01

    Objective A Rhesus monkey model was employed to study the radioprotective effects of a Toll-like receptor 5 agonist, CBLB502, against 7.0Gy whole-body irradiation of 60Co gamma-rays. Methods Thirty animals were assigned to a placebo treatment group, a WR-2721 positive control group, and three CBLB502 treatment groups (n=6 animals/group). Each animal was irradiated with 7.0Gy 60Co γ and given CBLB502 at 2.5, 10 and 40μg/kg, respectively in treatment groups, or WR-2721 at 30mg/kg, or physiologi...

  8. Single subcutaneous dosing of cefovecin in rhesus monkeys (Macaca mulatta)

    DEFF Research Database (Denmark)

    Bakker, J.; Thuesen, Line Risager; Braskamp, G.; Skaanild, Mette Tingleff; Ouwerling, B.; Langermans, J.A.M.; Bertelsen, Mads Frost

    2011-01-01

    Cefovecin is a third-generation cephalosporin approved for antibacterial treatment with a 14-day dosing interval in dogs and cats. This antibiotic may also be useful for zoo and wildlife veterinary medicine, because of its broad spectrum and long duration of activity. The aim of the study was to...... substantially different than for dogs and cats. Cefovecin rapidly reached C(max) which however was lower than most of the MIC levels and with a very short t½. Therefore, cefovecin is not recommended for treating skin wounds in rhesus monkeys....

  9. A Characterization of Aerosolized Sudan Virus Infection in African Green Monkeys, Cynomolgus Macaques, and Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Donald K. Nichols

    2012-10-01

    Full Text Available Filoviruses are members of the genera Ebolavirus, Marburgvirus, and “Cuevavirus”. Because they cause human disease with high lethality and could potentially be used as a bioweapon, these viruses are classified as CDC Category A Bioterrorism Agents. Filoviruses are relatively stable in aerosols, retain virulence after lyophilization, and can be present on contaminated surfaces for extended periods of time. This study explores the characteristics of aerosolized Sudan virus (SUDV Boniface in non-human primates (NHP belonging to three different species. Groups of cynomolgus macaques (cyno, rhesus macaques (rhesus, and African green monkeys (AGM were challenged with target doses of 50 or 500 plaque-forming units (pfu of aerosolized SUDV. Exposure to either viral dose resulted in increased body temperatures in all three NHP species beginning on days 4–5 post-exposure. Other clinical findings for all three NHP species included leukocytosis, thrombocytopenia, anorexia, dehydration, and lymphadenopathy. Disease in all of the NHPs was severe beginning on day 6 post-exposure, and all animals except one surviving rhesus macaque were euthanized by day 14. Serum alanine transaminase (ALT and aspartate transaminase (AST concentrations were elevated during the course of disease in all three species; however, AGMs had significantly higher ALT and AST concentrations than cynos and rhesus. While all three species had detectable viral load by days 3-4 post exposure, Rhesus had lower average peak viral load than cynos or AGMs. Overall, the results indicate that the disease course after exposure to aerosolized SUDV is similar for all three species of NHP.

  10. Magnitude and Diversity of Cytotoxic-T-Lymphocyte Responses Elicited by Multiepitope DNA Vaccination in Rhesus Monkeys

    OpenAIRE

    Subbramanian, Ramu A.; Kuroda, Marcelo J.; Charini, William A.; Barouch, Dan H.; Costantino, Cristina; Santra, Sampa; Schmitz, Jörn E.; Martin, Kristi L.; Lifton, Michelle A.; Gorgone, Darci A.; Shiver, John W.; Letvin, Norman L.

    2003-01-01

    In an effort to develop an AIDS vaccine that elicits high-frequency cytotoxic-T-lymphocyte (CTL) responses with specificity for a diversity of viral epitopes, we explored two prototype multiepitope plasmid DNA vaccines in the simian-human immunodeficiency virus/rhesus monkey model to determine their efficiency in priming for such immune responses. While a simple multiepitope vaccine construct demonstrated limited immunogenicity in monkeys, this same multiepitope genetic sequence inserted into...

  11. IL-15 increases the frequency of effector memory CD8+ T cells in rhesus monkeys immunized with HIV vaccine

    OpenAIRE

    Li, Shirui; Qi, Xiangrong; Gao, Yingying; Hao, Yanling; Cui, Lianxian; Ruan, Li; He, Wei

    2010-01-01

    Several studies have suggested that interleukin (IL)-15 is a promising adjuvant that promotes cellular immunity when administered with human immunodeficiency virus (HIV) vaccine. Here we evaluated the effect of IL-15 plasmid on HIV-specific immune responses, especially cellular immunity, in eight rhesus monkeys. These monkeys were immunized three times with HIV DNA vaccine with or without IL-15 plasmid and boosted with recombinant Tiantan strain vaccinia virus-based HIV vaccine (rTV) 22 weeks...

  12. Effects of selective neonatal temporal lobe lesions on socioemotional behavior in infant rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Bachevalier, J; Málková, L; Mishkin, M

    2001-06-01

    Normal infant monkeys and infant monkeys with neonatal damage to either the medial temporal lobe or the inferior temporal visual area were assessed in dyadic social interactions at 2 and 6 months of age. Unlike the normal infant monkeys, which developed strong affiliative bonds and little or no behavioral disturbances, the lesioned monkeys (each of which was observed with an unoperated control) exhibited socioemotional abnormalities and aberrant behaviors. The socioemotional changes predominated at 6 months of age and were particularly severe in monkeys with medial temporal lesions. In both the pattern and time course, the socioemotional deficits produced by the neonatal medial temporal lesions bear a striking resemblance to the behavioral syndrome in children with autism. Further analysis of these lesion-induced abnormalities in nonhuman primates may therefore provide insight into this debilitating human developmental disorder. PMID:11439445

  13. Effects of anesthesia upon 18F-FDG uptake in rhesus monkey brains

    International Nuclear Information System (INIS)

    The kinetics of 18F-fluorodeoxyglucose (18F-FDG) in the monkey brain were monitored, and comparisons were made between the conscious state and when under ketamine and pentobarbital anesthesia. Rhesus monkeys were intravenously injected with 18F-FDG and followed by 60 min of PET scanning. In the conscious state, the 18F-FDG concentration reached a plateau 5 min after intravenous injection. Under ketamine anesthesia, the 18F-FDG concentration gradually increased with time in all monitored regions. At 60 min after injection, the concentration in the striatum was about 3.2 times greater than that in the conscious state, and about 4.5 times greater in the cerebral cortex. Under pentobarbital anesthesia, the 18F-FDG concentration in the occipital cortex was slightly lower. These findings demonstrate that 18F-FDG concentration in the monkey brain is significantly affected by anesthesia. The results also imply the existence of a short-term regulation mechanism for hexokinase activity in intact monkey brain. (author)

  14. Interactions between Δ(9)-tetrahydrocannabinol and heroin: self-administration in rhesus monkeys.

    Science.gov (United States)

    Li, Jun-Xu; Koek, Wouter; France, Charles P

    2012-12-01

    The cannabinoid receptor agonist Δ(9)-tetrahydrocannabinol (THC) enhances the antinociceptive effects of µ-opioid receptor agonists, raising the possibility of using a combination of THC and opioids for treating pain. This study examined the effects of noncontingent and contingent administration of THC on intravenous heroin self-administration in rhesus monkeys. Self-administration of different unit doses of heroin (0.0001-0.1 mg/kg/infusion) generated a typical inverted U-shaped dose-response curve. In one experiment (n=4), noncontingent THC (0.1-1.0 mg/kg) dose dependently shifted the heroin dose-response curve downward in three monkeys and slightly leftward in one monkey. In a second experiment (n=4), monkeys could self-administer THC alone (0.0032-0.032 mg/kg/infusion), heroin alone, or a mixture of THC and heroin. THC alone did not maintain responding above that obtained with saline; however, increasing the THC dose with heroin dose dependently decreased the number of infusions received and the rate of responding, as compared with data that were obtained with heroin alone. These results indicate that THC does not significantly enhance the positive reinforcing effects of heroin, further supporting the view that combining cannabinoid and opioid receptor agonists (e.g. for treating pain) does not increase, and might decrease, the abuse liability of individual drugs. PMID:23044830

  15. Attenuation of cocaine self-administration by chronic oral phendimetrazine in rhesus monkeys.

    Science.gov (United States)

    Czoty, P W; Blough, B E; Fennell, T R; Snyder, R W; Nader, M A

    2016-06-01

    Chronic treatment with the monoamine releaser d-amphetamine has been consistently shown to decrease cocaine self-administration in laboratory studies and clinical trials. However, the abuse potential of d-amphetamine is an obstacle to widespread clinical use. Approaches are needed that exploit the efficacy of the agonist approach but avoid the abuse potential associated with dopamine releasers. The present study assessed the effectiveness of chronic oral administration of phendimetrazine (PDM), a pro-drug for the monoamine releaser phenmetrazine (PM), to decrease cocaine self-administration in four rhesus monkeys. Each day, monkeys pressed a lever to receive food pellets under a 50-response fixed-ratio (FR) schedule of reinforcement and self-administered cocaine (0.003-0.56 mg/kg per injection, i.v.) under a progressive-ratio (PR) schedule in the evening. After completing a cocaine self-administration dose-response curve, sessions were suspended and PDM was administered (1.0-9.0 mg/kg, p.o., b.i.d.). Cocaine self-administration was assessed using the PR schedule once every 7 days while food-maintained responding was studied daily. When a persistent decrease in self-administration was observed, the cocaine dose-effect curve was re-determined. Daily PDM treatment decreased cocaine self-administration by 30-90% across monkeys for at least 4 weeks. In two monkeys, effects were completely selective for cocaine. Tolerance developed to initial decreases in food-maintained responding in the third monkey and in the fourth subject, fluctuations were observed that were lower in magnitude than effects on cocaine self-administration. Cocaine dose-effect curves were shifted down and/or rightward in three monkeys. These data provide further support for the use of agonist medications for cocaine abuse, and indicate that the promising effects of d-amphetamine extend to a more clinically viable pharmacotherapy. PMID:26964683

  16. Donepezil- and scopolamine-induced rCMRglu changes assessed by PET in conscious rhesus monkeys

    International Nuclear Information System (INIS)

    [18F]Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is a useful tool for measuring the regional cerebral metabolic rate of glucose (rCMRglu), which is an index of neuronal activity. Donepezil, an acetylcholine esterase inhibitor (AChEI), has been recommended as a treatment option for patients with Alzheimer's disease (AD). We aimed to characterize the effects of donepezil on rCMRglu using FDG-PET in non-human primates. We investigated the effects of administration of donepezil (500 μg/kg, intramuscularly (i.m.)), the non-selective muscarinic ACh receptor antagonist scopolamine (30 μg/kg, i.m.), and the coadministration of both drugs on the rCMRglu of conscious young rhesus monkeys. Donepezil increased the rCMRglu in all regions of interest except in the thalamus. Scopolamine treatment also increased the rCMRglu in all regions of interest except the cerebellum and thalamus. However, these effects disappeared with coadministration of the drugs. This PET study showed that administration of donepezil or scopolamine alone increased the rCMRglu in conscious rhesus monkeys. We also found that the donepezil-induced increase was abolished by simultaneous administration of scopolamine, suggesting that muscarinic ACh receptor function plays an important role in the effect of donepezil. (author)

  17. The induction by ionizing radiation of chromosomal aberrations in rhesus monkey pre-meiotic germ cells

    International Nuclear Information System (INIS)

    The induction of reciprocal translocations in rhesus monkey stem-cell spermatogonia was studied using multivalent analysis at metaphase of primary spermatocytes. Animals were exposed to 1 Gy γ-rays at dose rates of 140 and 0.2 mGy/min or to 0.25 Gy acute 2 MeV neutrons. Reduction of the dose from 140 mGy/min to 0.2 mGy/min did not result in a lowering of the frequencies of recovered translocations of 0.43 %. The neutron data indicated an RBE (neutrons vs. X-rays) of 2.1, which is clearly lower than the value of 4 obtained in the mouse. It is made plausible that in general mammalian species with high sensitivities for the cytotoxic effects of ionizing radiation, such as the rhesus monkey, will exhibit relatively high threshold dose rates below which no further reduction in aberration yield occurs, whereas in more resistant species, such as the mouse, the threshold dose rate will be at a very low level. Similarly, resistant species will show relatively high RBNE values for neutron irradiation and sensitive species low ones. (author). 36 refs.; 2 tabs

  18. A simple model of radial nerve injury in the rhesus monkey to evaluate peripheral nerve repair.

    Science.gov (United States)

    Wang, Dong; Huang, Xijun; Fu, Guo; Gu, Liqiang; Liu, Xiaolin; Wang, Honggang; Hu, Jun; Yi, Jianhua; Niu, Xiaofeng; Zhu, Qingtang

    2014-05-15

    Current research on bone marrow stem cell transplantation and autologous or xenogenic nerve transplantation for peripheral nerve regeneration has mainly focused on the repair of peripheral nerve defects in rodents. In this study, we established a standardized experimental model of radial nerve defects in primates and evaluated the effect of repair on peripheral nerve injury. We repaired 2.5-cm lesions in the radial nerve of rhesus monkeys by transplantation of autografts, acellular allografts, or acellular allografts seeded with autologous bone marrow stem cells. Five months after surgery, regenerated nerve tissue was assessed for function, electrophysiology, and histomorphometry. Postoperative functional recovery was evaluated by the wrist-extension test. Compared with the simple autografts, the acellular allografts and allografts seeded with bone marrow stem cells facilitated remarkable recovery of the wrist-extension functions in the rhesus monkeys. This functional improvement was coupled with radial nerve distal axon growth, a higher percentage of neuron survival, increased nerve fiber density and diameter, increased myelin sheath thickness, and increased nerve conduction velocities and peak amplitudes of compound motor action potentials. Furthermore, the quality of nerve regeneration in the bone marrow stem cells-laden allografts group was comparable to that achieved with autografts. The wrist-extension test is a simple behavioral method for objective quantification of peripheral nerve regeneration. PMID:25206757

  19. A simple model of radial nerve injury in the rhesus monkey to evaluate peripheral nerve repair

    Institute of Scientific and Technical Information of China (English)

    Dong Wang; Qingtang Zhu; Xijun Huang; Guo Fu; Liqiang Gu; Xiaolin Liu; Honggang Wang; Jun Hu; Jianhua Yi; Xiaofeng Niu

    2014-01-01

    Current research on bone marrow stem cell transplantation and autologous or xenogenic nerve transplantation for peripheral nerve regeneration has mainly focused on the repair of peripher-al nerve defects in rodents. In this study, we established a standardized experimental model of radial nerve defects in primates and evaluated the effect of repair on peripheral nerve injury. We repaired 2.5-cm lesions in the radial nerve of rhesus monkeys by transplantation of autografts, acellular allografts, or acellular allografts seeded with autologous bone marrow stem cells. Five months after surgery, regenerated nerve tissue was assessed for function, electrophysiology, and histomorphometry. Postoperative functional recovery was evaluated by the wrist-extension test. Compared with the simple autografts, the acellular allografts and allografts seeded with bone marrow stem cells facilitated remarkable recovery of the wrist-extension functions in the rhesus monkeys. This functional improvement was coupled with radial nerve distal axon growth, a higher percentage of neuron survival, increased nerve fiber density and diameter, increased myelin sheath thickness, and increased nerve conduction velocities and peak amplitudes of compound motor action potentials. Furthermore, the quality of nerve regeneration in the bone marrow stem cells-laden allografts group was comparable to that achieved with autografts. The wrist-extension test is a simple behavioral method for objective quantification of peripheral nerve regeneration.

  20. Autophagy in retinal ganglion cells in a rhesus monkey chronic hypertensive glaucoma model.

    Directory of Open Access Journals (Sweden)

    Shuifeng Deng

    Full Text Available Primary open angle glaucoma (POAG is a neurodegenerative disease characterized by physiological intraocular hypertension that causes damage to the retinal ganglion cells (RGCs. In the past, RGC damage in POAG was suggested to have been attributed to RGC apoptosis. However, in the present study, we applied a model closer to human POAG through the use of a chronic hypertensive glaucoma model in rhesus monkeys to investigate whether another mode of progressive cell death, autophagy, was activated in the glaucomatous retinas. First, in the glaucomatous retinas, the levels of LC3B-II, LC3B-II/LC3B-I and Beclin 1 increased as demonstrated by Western blot analyses, whereas early or initial autophagic vacuoles (AVi and late or degraded autophagic vacuoles (AVd accumulated in the ganglion cell layer (GCL and in the inner plexiform layer (IPL as determined by transmission electron microscopy (TEM analysis. Second, lysosome activity and autophagosome-lysosomal fusion increased in the RGCs of the glaucomatous retinas, as demonstrated by Western blotting against lysosome associated membrane protein-1 (LAMP1 and double labeling against LC3B and LAMP1. Third, apoptosis was activated in the glaucomatous eyes with increased levels of caspase-3 and cleaved caspase-3 and an increased number of TUNEL-positive RGCs. Our results suggested that autophagy was activated in RGCs in the chronic hypertensive glaucoma model of rhesus monkeys and that autophagy may have potential as a new target for intervention in glaucoma treatment.

  1. Placental transfer and metabolism of 17 alpha-ethynylestradiol-17 beta and estradiol-17 beta in the rhesus monkey

    International Nuclear Information System (INIS)

    The synthetic estrogen component of many oral contraceptives, 17 alpha-ethynylestradiol-17 beta (EE2) and the naturally occurring estrogen, estradiol-17 beta (E2) were studied in four pregnant rhesus monkeys (71% term: 108-121 days gestational age). Under ketamine anesthesia, catheters were implanted in the maternal femoral artery and fetal interplacental artery. After simultaneous i.v. administration of [3H]EE2-[14C]E2 to the maternal animal, serial blood samples were drawn from both mother and fetus. The estrogens and metabolites were identified and quantified by the comigration of radioactivity with reference standards in several high-performance liquid chromatography systems and subsequent selective enzyme hydrolysis of the conjugates. Only estrone (E1), E1 sulfate, EE2 and EE2-3 sulfate were observed in the fetal circulation, whereas the major radiolabeled compounds in the maternal circulation consisted of the above plus E2, E1 glucuronide and EE2-3 glucuronide. In order to determine whether the placenta could convert E2 to its metabolite E1, the placentas of three term rhesus monkeys were perfused in situ via the umbilical artery with 120 ml (15 ml/min) of Hanks' balanced salt solution (pH 7.4) containing [3H]E2. High-performance liquid chromatographic analysis of umbilical vein samples revealed that 96% of the E2 was metabolized to E1. These studies indicate that the placenta can metabolize the potent naturally occurring estrogen E2 to the less potent E1. In contrast, the synthetic estrogen EE2 does not undergo this placental metabolic conversion and thus enters the fetal circulation as the parent compound

  2. Differential Antagonism of Cocaine Self-Administration and Cocaine-Induced Disruptions of Learning by Haloperidol in Rhesus Monkeys

    Science.gov (United States)

    Winsauer, Peter J.; Moerschbaecher, Joseph M.; Roussell, Alison M.

    2008-01-01

    Six rhesus monkeys responding under a three-component multiple schedule were administered haloperidol to determine its effects on cocaine self-administration and on cocaine's disruptive effects on the repeated acquisition and performance of response chains. In the absence of haloperidol, 0.0032 - 0.032 mg/kg/infusion of cocaine increased response…

  3. Effects of U-75875, a peptidomimetic inhibitor of retroviral proteases, on simian immunodeficiency virus infection in rhesus monkeys.

    OpenAIRE

    Martin, L. N.; Soike, K F; Murphey-Corb, M; Bohm, R P; Roberts, E. D.; Kakuk, T J; Thaisrivongs, S; Vidmar, T J; Ruwart, M. J.; Davio, S R

    1994-01-01

    U-75875 inhibits human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus (SIV) proteases and blocks Gag-Pol protein processing and viral maturation and replication in vitro. Rhesus monkeys were treated with vehicle alone or with formulated U-75875 at doses of 7 or 20 mg/kg of body weight per day for 26 days by continuous intravenous infusion beginning 6 h prior to intravenous inoculation with 10 monkey 50% infectious doses of SIV Delta B670, and the monkeys were monitored...

  4. Selective blockade of CD28-mediated T cell costimulation protects rhesus monkeys against acute fatal experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Haanstra, Krista G; Dijkman, Karin; Bashir, Noun; Bauer, Jan; Mary, Caroline; Poirier, Nicolas; Baker, Paul; Crossan, Claire L; Scobie, Linda; 't Hart, Bert A; Vanhove, Bernard

    2015-02-15

    Costimulatory and coinhibitory receptor-ligand pairs on T cells and APC control the immune response. We have investigated whether selective blockade of CD28-CD80/86 costimulatory interactions, which preserves the coinhibitory CTLA4-CD80/86 interactions and the function of regulatory T (Treg) cells, abrogates the induction of experimental autoimmune encephalomyelitis (EAE) in rhesus monkeys. EAE was induced by intracutaneous immunization with recombinant human myelin oligodendrocyte glycoprotein (rhMOG) in CFA on day 0. FR104 is a monovalent, PEGylated-humanized Fab' Ab fragment against human CD28, cross-reactive with rhesus monkey CD28. FR104 or placebo was administered on days 0, 7, 14, and 21. FR104 levels remained high until the end of the study (day 42). Placebo-treated animals all developed clinical EAE between days 12 and 27. FR104-treated animals did not develop clinical EAE and were sacrificed at the end of the study resulting in a significantly prolonged survival. FR104 treatment diminished T and B cell responses against rhMOG, significantly reduced CNS inflammation and prevented demyelination. The inflammatory profile in the cerebrospinal fluid and brain material was also strongly reduced. Recrudescence of latent virus was investigated in blood, spleen, and brain. No differences between groups were observed for the β-herpesvirus CMV and the polyomaviruses SV40 and SA12. Cross-sectional measurement of lymphocryptovirus, the rhesus monkey EBV, demonstrated elevated levels in the blood of FR104-treated animals. Blocking rhesus monkey CD28 with FR104 mitigated autoreactive T and B cell activation and prevented CNS pathology in the rhMOG/CFA EAE model in rhesus monkeys. PMID:25589073

  5. Exploring the extent and function of higher-order auditory cortex in rhesus monkeys.

    Science.gov (United States)

    Poremba, Amy; Mishkin, Mortimer

    2007-07-01

    Just as cortical visual processing continues far beyond the boundaries of early visual areas, so too does cortical auditory processing continue far beyond the limits of early auditory areas. In passively listening rhesus monkeys examined with metabolic mapping techniques, cortical areas reactive to auditory stimulation were found to include the entire length of the superior temporal gyrus (STG) as well as several other regions within the temporal, parietal, and frontal lobes. Comparison of these widespread activations with those from an analogous study in vision supports the notion that audition, like vision, is served by several cortical processing streams, each specialized for analyzing a different aspect of sensory input, such as stimulus quality, location, or motion. Exploration with different classes of acoustic stimuli demonstrated that most portions of STG show greater activation on the right than on the left regardless of stimulus class. However, there is a striking shift to left-hemisphere "dominance" during passive listening to species-specific vocalizations, though this reverse asymmetry is observed only in the region of temporal pole. The mechanism for this left temporal pole "dominance" appears to be suppression of the right temporal pole by the left hemisphere, as demonstrated by a comparison of the results in normal monkeys with those in split-brain monkeys. PMID:17321703

  6. Pharmacokinetics of isoflavones from soy infant formula in neonatal and adult rhesus monkeys.

    Science.gov (United States)

    Doerge, Daniel R; Woodling, Kellie A; Churchwell, Mona I; Fleck, Stefanie C; Helferich, William G

    2016-06-01

    Consumption of soy infant formula represents a unique exposure scenario in which developing children ingest a mixture of endocrine-active isoflavones along with a substantial portion of daily nutrition. Genistein and daidzein were administered as glucoside conjugates to neonatal rhesus monkeys in a fortified commercial soy formula at 5, 35, and 70 days after birth. A single gavage dosing with 10 mg/kg bw genistein and 6 mg/kg bw daidzein was chosen to represent the upper range of typical daily consumption and to facilitate complete pharmacokinetic measurements for aglycone and total isoflavones and equol. Adult monkeys were also gavaged with the same formula solution at 2.8 and 1.6 mg/kg bw genistein and daidzein, respectively, and by IV injection with isoflavone aglycones (5.2 and 3.2 mg/kg bw, respectively) to determine absolute bioavailability. Significant differences in internal exposure were observed between neonatal and adult monkeys, with higher values for dose-adjusted AUC and Cmax of the active aglycone isoflavones in neonates. The magnitude and frequency of equol production by the gut microbiome were also significantly greater in adults. These findings are consistent with immaturity of metabolic and/or physiological systems in developing non-human primates that reduces total clearance of soy isoflavones from the body. PMID:27084109

  7. Histopathologic findings of pulmonary acariasis in a rhesus monkeys breeding unit Aspectos histopatológicos da acaríase pulmonar em uma criação de macacos rhesus

    OpenAIRE

    Márcia Cristina R. Andrade; Renato S. Marchevsky

    2007-01-01

    Histological lesions in the lungs of rhesus monkeys (Macaca mulatta) related with Pneumonyssus simicola were evidenced. The most prominent pathologic alterations included numerous thin-walled cysts 1-5 mm diameter scattered throughout the lungs, bronchiolitis, peribronchiolitis where the mites were found associated with pigmented and non-pigmented materials. Our study included data from 347 rhesus monkeys submitted to necropsies during 20 years. Four adult debilitated animals were found with ...

  8. Immune senescence in old and very old rhesus monkeys: reduced antibody response to influenza vaccination

    OpenAIRE

    Coe, Christopher L.; Lubach, Gabriele R.; Kinnard, Jeanne

    2012-01-01

    The health of old monkeys usually begins to deteriorate by 20 years of age, coinciding with the onset of a slowly progressing immune senescence. Changes in lymphocyte subsets and responses to several antigens have been characterized in geriatric primates, but systematic research has not been conducted on vaccination against influenza virus, a topic of considerable clinical concern for elderly humans. Antibody responses were significantly reduced to primary immunizations in old monkeys, but by...

  9. Variation of T cell subset during acute rejection after liver transplantation in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    Ran Jiang-hua; Liu Jing; Zhang Xi-bing; Zhang Sheng-ning; Wu Shu-yuan; Li Lai-bang; Li Wang; Li Li

    2014-01-01

    Abstract BACKGROUND: Looking for the early diagnosis of acute rejection indicators after liver transplantation can assess the risk after liver transplantation quickly and effectively, and T lymphocytes play the significant role in acute rejection. OBJECTIVE:To observe the relationship between acute rejection and variation of expression of T cel subset in blood after liver transplantation in rhesus monkey. METHODS: The sixteen liver transplant models in rhesus monkey which were constructed successfuly by the method of “double-cuff and one support tube” were divided into two groups randomly: experiment group (no treated by immunosuppressant in perioperative period) and control group (treated by immunosuppressant in perioperative period). Then the blood specimen and liver tissue respectively were colected at 6, 12, 24 and 72 hours after operation. The levels of alanine transferase, aspartate aminotransferase, and total bilirubin were detected with the fuly automatic biochemical analyser. The levels of CD4+/CD8+were tested by flow cytometry. The liver tissue in rhesus monkey after liver transplantation was detected by hematoxylin-eosin staining. The degree of acute rejection was evaluated by Banff Score System. RESULTS AND CONCLUSION: Acute rejection appeared in the experiment group at 12, 24, and 72 hours after liver transplantation. Levels of alanine transferase, aspartate aminotransferase, and total bilirubin were significantly higher in the experimental group than in the control group at 24 and 72 hours after transplantation (P < 0.05). The expression of CD4+/CD8+of the experiment group and control group began to rise at 6 hours after surgery, but the experiment group increased the most obvious. CD4+/CD8+ expression was significantly greater in the experimental group than in the control group at 24 and 72 hours after transplantation (P < 0.05). Morphological pathology was severer, and Banff score was higher in the experiment group than in the control group at

  10. A comparative study of the frequencies of radiation-induced chromosome aberrations in somatic and germ cells of the Rhesus monkey (Macaca mulatta)

    International Nuclear Information System (INIS)

    Frequencies of radiation-induced chromosome aberrations in spermatogonia peripheral blood lymphocytes and bone-marrow cells of the rhesus monkey (Macaca mulatta) and in human blood lymphocytes, where determined at different exposures of X-rays. The dose-response curve for the induction of reciprocal translocations in spermatogonia suggested a 'hump' at about 200 rad. The absolute frequencies of chromosome aberrations in somatic and germ cells of the rhesus monkey were low in comparison with most other mammalian species and the ratio between aberrations in the two tissues was 25 to 1 at the 100 rad level. Although the numbers of 'effective chromosome arms' in man and rhesus monkey are similar (81 vs. 83), the rhesus monkey showed a lower rate of induction of dicentrics in blood lymphocytes than man at all doses reaching statistical significance at the 300 rad level

  11. Aging: Lessons for Elderly People from Monkeys.

    Science.gov (United States)

    Crockford, Catherine

    2016-07-11

    As life expectancy increases, health in the elderly is a growing issue. Health is linked to remaining socially active, but the elderly typically narrow their social networks. The social life of aging monkeys shows interesting parallels, indicating social patterns may be rooted in evolution. PMID:27404240

  12. Associations between Parity, Hair Hormone Profiles during Pregnancy and Lactation, and Infant Development in Rhesus Monkeys (Macaca mulatta.

    Directory of Open Access Journals (Sweden)

    Amanda M Dettmer

    Full Text Available Studies examining hormones throughout pregnancy and lactation in women have been limited to single, or a few repeated, short-term measures of endocrine activity. Furthermore, potential differences in chronic hormonal changes across pregnancy/lactation between first-time and experienced mothers are not well understood, especially as they relate to infant development. Hormone concentrations in hair provide long-term assessments of hormone production, and studying these measures in non-human primates allows for repeated sampling under controlled conditions that are difficult to achieve in humans. We studied hormonal profiles in the hair of 26 female rhesus monkeys (Macaca mulatta, n=12 primiparous, to determine the influences of parity on chronic levels of cortisol (hair cortisol concentration, HCC and progesterone (hair progesterone concentration, HPC during early- to mid-pregnancy (PREG1, in late pregnancy/early lactation (PREG2/LACT1, and in peak lactation (LACT2. We also assessed infants' neurobehavioral development across the first month of life. After controlling for age and stage of pregnancy at the first hair sampling period, we found that HCCs overall peaked in PREG2/LACT1 (p=0.02, but only in primiparous monkeys (p<0.001. HPCs declined across pregnancy and lactation for all monkeys (p<0.01, and primiparous monkeys had higher HPCs overall than multiparous monkeys (p=0.02. Infants of primiparous mothers had lower sensorimotor reflex scores (p=0.02 and tended to be more irritable (p=0.05 and less consolable (p=0.08 in the first month of life. Moreover, across all subjects, HCCs in PREG2/LACT1 were positively correlated with irritability (r(s=0.43, p=0.03 and negatively correlated with sensorimotor scores (r(s=-0.41, p=0.04. Together, the present results indicate that primiparity influences both chronic maternal hormonal profiles and infant development. These effects may, in part, reflect differential reproductive and maternal effort in

  13. Aging and iron accumulation in the monkey brain

    International Nuclear Information System (INIS)

    Iron is deposited in the mammalian brain with a characteristic distribution, its amount increasing with aging. The relative abundance of iron in the globus pallidus, substantia nigra and putamen is thought to be responsible for the hypointensity of these nuclei on T2-weighted MR images, due to magnetic susceptibility effects. However, no quantitative correlation between iron content and hypointensity has been made to confirm this hypothesis. Two young (1-year-old) and two older (18-year-old) rhesus monkeys were studied with MR imaging at different field strengths (0.5, 1.5, 2.0 T). MR signal intensities from different anatomic structures were measured on T2-weighted coronal images (2,6000/80 [repetition time msec/echo time msec]). At completion of the MR studies, the monkeys were killed, coronal brain sections were stained for iron (Perls method), and optical densities of anatomic structures were measured. A quantitative correlation between the iron content and the signal intensity decrease was found on T2-weighted images in both deep and superficial cerebral structures. The detectability of magnetic susceptibility effects in a single structure is determined by the amount of iron present, with the threshold being inversely correlated to the strength of the magnetic field

  14. Lorcaserin Reduces the Discriminative Stimulus and Reinforcing Effects of Cocaine in Rhesus Monkeys.

    Science.gov (United States)

    Collins, Gregory T; Gerak, Lisa R; Javors, Martin A; France, Charles P

    2016-01-01

    Cocaine abuse and obesity are serious public health problems, and studies suggest that both dopamine and serotonin systems are involved in regulating the consumption of drugs and food. Lorcaserin has serotonin (5-HT)2C receptor agonist actions, is approved by the U.S. Food and Drug Administration for treating obesity, and might be effective for treating cocaine abuse. These studies characterized the pharmacokinetic and behavioral profiles of lorcaserin (intragastric administration) and determined the effectiveness of lorcaserin to alter discriminative stimulus and reinforcing effects of cocaine (intravenous administration) in rhesus monkeys. Administered acutely, lorcaserin dose-dependently increased the occurrence of yawning while decreasing spontaneous activity and operant responding for food. These effects appeared within 30-60 minutes of administration and began to dissipate by 240 minutes, a time course closely matching plasma concentrations of lorcaserin. In monkeys discriminating cocaine from saline, lorcaserin alone did not occasion cocaine-appropriate responding but shifted the cocaine dose-response curve to the right and down in two of three monkeys. When administered acutely, lorcaserin dose-dependently decreased the rate at which monkeys responded for infusions of cocaine. When administered chronically, 3.2 mg/kg lorcaserin reduced the rate of cocaine-maintained responding by 50% for the duration of a 14-day treatment period. Together, these results show that lorcaserin attenuates the discriminative stimulus effects of cocaine after acute administration and the reinforcing effects of cocaine after acute and repeated administration, consistent with the view that it might have utility in treating cocaine abuse. PMID:26534942

  15. Concurrent determination of bisphenol A pharmacokinetics in maternal and fetal rhesus monkeys

    International Nuclear Information System (INIS)

    Bisphenol A (BPA) is an important industrial chemical used as the monomer for polycarbonate plastic and in epoxy resins for food can liners. Worldwide biomonitoring studies consistently find a high prevalence of BPA conjugates in urine (> 90%) in amounts consistent with aggregate exposure at levels below 1 μg/kg bw/d. The current study used LC/MS/MS to measure concurrently the pharmacokinetics of aglycone (active) and conjugated (inactive) deuterated BPA (d6) in maternal and fetal rhesus monkey serum, amniotic fluid, and placenta following intravenous injection in the dam (100 μg/kg bw). Internal exposures of the fetus to aglycone d6-BPA (serum AUC) were attenuated by maternal, placental, and fetal Phase II metabolism to less than half that in the dam. Levels of aglycone and conjugated d6-BPA measured in whole placenta were consistent with a role in metabolic detoxification. The monotonic elimination of aglycone d6-BPA from the fetal compartment accompanied by persistent conjugate levels provides further evidence arguing against the hypothesis that BPA conjugates are selectively deconjugated by either the placenta or fetus. These results also provide benchmarks to guide the interpretation of human cord blood, amniotic fluid, and placenta sampling and measurement strategies as a basis for estimating fetal exposures to BPA. This study in a non-human primate model provides additional pharmacokinetic data for use in PBPK modeling of perinatal exposures to BPA from food contact, medical devices, and other environmental sources. - Highlights: ► Maternal, placental, and fetal Phase II metabolism attenuate fetal exposure to BPA. ► Serum AUC for aglycone BPA in fetal monkeys is less than half of that in the dam. ► BPA profiles in monkey fetus rule out selective deconjugation and accumulation. ► BPA levels in monkey placenta are similar to other metabolically active tissues. ► Some published human cord blood data for BPA are inconsistent with these measurements

  16. Concurrent determination of bisphenol A pharmacokinetics in maternal and fetal rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Patterson, Tucker A. [Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Twaddle, Nathan C. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Roegge, Cindy S. [Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Callicott, Ralph J. [U.S. Food and Drug Administration and Priority One Services Corp, Jefferson, AR 72079 (United States); Fisher, Jeffrey W. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Doerge, Daniel R., E-mail: daniel.doerge@fda.hhs.gov [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States)

    2013-02-15

    Bisphenol A (BPA) is an important industrial chemical used as the monomer for polycarbonate plastic and in epoxy resins for food can liners. Worldwide biomonitoring studies consistently find a high prevalence of BPA conjugates in urine (> 90%) in amounts consistent with aggregate exposure at levels below 1 μg/kg bw/d. The current study used LC/MS/MS to measure concurrently the pharmacokinetics of aglycone (active) and conjugated (inactive) deuterated BPA (d6) in maternal and fetal rhesus monkey serum, amniotic fluid, and placenta following intravenous injection in the dam (100 μg/kg bw). Internal exposures of the fetus to aglycone d6-BPA (serum AUC) were attenuated by maternal, placental, and fetal Phase II metabolism to less than half that in the dam. Levels of aglycone and conjugated d6-BPA measured in whole placenta were consistent with a role in metabolic detoxification. The monotonic elimination of aglycone d6-BPA from the fetal compartment accompanied by persistent conjugate levels provides further evidence arguing against the hypothesis that BPA conjugates are selectively deconjugated by either the placenta or fetus. These results also provide benchmarks to guide the interpretation of human cord blood, amniotic fluid, and placenta sampling and measurement strategies as a basis for estimating fetal exposures to BPA. This study in a non-human primate model provides additional pharmacokinetic data for use in PBPK modeling of perinatal exposures to BPA from food contact, medical devices, and other environmental sources. - Highlights: ► Maternal, placental, and fetal Phase II metabolism attenuate fetal exposure to BPA. ► Serum AUC for aglycone BPA in fetal monkeys is less than half of that in the dam. ► BPA profiles in monkey fetus rule out selective deconjugation and accumulation. ► BPA levels in monkey placenta are similar to other metabolically active tissues. ► Some published human cord blood data for BPA are inconsistent with these measurements.

  17. Characterization of the Sweet Taste Receptor Tas1r2 from an Old World Monkey Species Rhesus Monkey and Species-Dependent Activation of the Monomeric Receptor by an Intense Sweetener Perillartine

    Science.gov (United States)

    Cai, Chenggu; Jiang, Hua; Li, Lei; Liu, Tianming; Song, Xuejie; Liu, Bo

    2016-01-01

    Sweet state is a basic physiological sensation of humans and other mammals which is mediated by the broadly acting sweet taste receptor-the heterodimer of Tas1r2 (taste receptor type 1 member 2) and Tas1r3 (taste receptor type 1 member 3). Various sweeteners interact with either Tas1r2 or Tas1r3 and then activate the receptor. In this study, we cloned, expressed and functionally characterized the taste receptor Tas1r2 from a species of Old World monkeys, the rhesus monkey. Paired with the human TAS1R3, it was shown that the rhesus monkey Tas1r2 could respond to natural sugars, amino acids and their derivates. Furthermore, similar to human TAS1R2, rhesus monkey Tas1r2 could respond to artificial sweeteners and sweet-tasting proteins. However, the responses induced by rhesus monkey Tas1r2 could not be inhibited by the sweet inhibitor amiloride. Moreover, we found a species-dependent activation of the Tas1r2 monomeric receptors of human, rhesus monkey and squirrel monkey but not mouse by an intense sweetener perillartine. Molecular modeling and sequence analysis indicate that the receptor has the conserved domains and ligand-specific interactive residues, which have been identified in the characterized sweet taste receptors up to now. This is the first report of the functional characterization of sweet taste receptors from an Old World monkey species. PMID:27479072

  18. Cardiovascular results from a rhesus monkey flown aboard the Cosmos 1514 spaceflight

    Science.gov (United States)

    Sandler, H.; Hines, J.; Benjamin, B. A.; Halpryn, B. M.; Krotov, V. P.

    1987-01-01

    The results of the Cosmos 1514 cardiovascular experiment, in which the blood flow to the head and the carotid pressure of a rhesus monkey were measured during the 5-d spaceflight, are reported. A single cylindrical probe containing both pressure and flow transducers was chronically implanted as a cuff around the left common carotid artery; measurements were obtained for 4 min every 2 h and compared to identical recordings obtained during a preflight control period and during 12 h on a launch pad. Immediately on its insertion into orbit, mean arterial pressure increased by 10 percent and has maintained a 16-27 percent increase over the first few hours of flight before returning to baseline level. Blood flow showed reciprocal changes to pressure on orbital insertion. Cardiovascular system changes persisted into the second day of flight, with the signs of adaptation appearing on days 3-5.

  19. In vitro biosynthesis of radioactive estradiol-17 beta, 17-glucosiduronate by rhesus monkey liver

    International Nuclear Information System (INIS)

    A method for the preparation of radioactive estradiol-17 beta, 17-glucosiduronate by incubating 3H-estradiol with rhesus monkey liver microsomal preparation in the presence of uridine diphosphoglucuronic acid is described. Small but significant amounts of the conjugate were also obtained from the 150,000 pellet and cytosol fractions. The addition of NADPH to the incubation media increased the yield of radioactive-estradiol-17 beta, 17-glucosiduronate perhaps by preserving the integrity of the C-17-hydroxyl group. As expected, the effect of the reduced nucleotide was more pronounced in the fractions other than the microsome. The biosynthesized conjugate was isolated and purified by multiple column chromatography and the structure was confirmed by derivative formation, enzyme hydrolysis and crystallization of the aglycone

  20. Partial protection of SIV-infected rhesus monkeys against superinfection with a heterologous SIV isolate

    Energy Technology Data Exchange (ETDEWEB)

    Korber, Bette [Los Alamos National Laboratory

    2009-01-01

    Although there is increasing evidence that individuals already infected with human immunodeficiency virus type 1 (HIV-1) can be infected with a heterologous strain of the virus, the extent of protection against superinfection conferred by the first infection and the biologic consequences of superinfection are not well understood. We explored these questions in the simian immunodeficiency virus (SIV)/rhesus monkey model of HIV-1/AIDS. We infected cohorts of rhesus monkeys with either SIVmac251 or SIVsmE660 and then exposed animals to the reciprocal virus through intrarectal inoculations. Employing a quantitative real-time PCR assay, we determined the replication kinetics of the two strains of virus for 20 weeks. We found that primary infection with a replication-competent virus did not protect against acquisition of infection by a heterologous virus but did confer relative control of the superinfecting virus. In animals that became superinfected, there was a reduction in peak replication and rapid control of the second virus. The relative susceptibility to superinfection was not correlated with CD4(+) T-cell count, CD4(+) memory T-cell subsets, cytokine production by virus-specific CD8(+) or CD4(+) cells, or neutralizing antibodies at the time of exposure to the second virus. Although there were transient increases in viral loads of the primary virus and a modest decline in CD4(+) T-cell counts after superinfection, there was no evidence of disease acceleration. These findings indicate that an immunodeficiency virus infection confers partial protection against a second immunodeficiency virus infection, but this protection may be mediated by mechanisms other than classical adaptive immune responses.

  1. Shock titration in the rhesus monkey: effects of opiate and nonopiate analgesics.

    Science.gov (United States)

    Bloss, J L; Hammond, D L

    1985-11-01

    This study evaluated the antinociceptive effects of several opiate and nonopiate analgesics in the rhesus monkey using a discrete trial shock titration paradigm. Morphine sulfate (1, 5 and 10 mg/kg i.m.) and codeine sulfate (3, 10 and 30 mg/kg i.m.) produced a significant and dose-dependent increase in mean shock threshold that was not accompanied by a significant increase in mean response latency. The mean number of shocks terminated was significantly decreased at the highest dose of each opiate. Aspirin (100 and 300 mg/kg p.o.) or ibuprofen (200 mg/kg p.o.) did not significantly increase mean shock threshold or mean response latency or decrease mean number of shocks terminated. However, 6 mg/kg i.m. of 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin-3-ol produced a significant increase in mean shock threshold and mean response latency with no significant effect on mean number of shocks terminated. The absence of any effects of a 2-mg/kg dose of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol and the severe side effects produced by 10 mg/kg prevented determination of its dose-response relationship. Diazepam (0.5, 2 and 8 mg/kg i.m.) produced a significant, dose-dependent increase in mean shock threshold and a significant increase in mean response latency with no consistent or significant effect on mean number of shocks terminated. Doses of 2 and 8 mg/kg of diazepam also produced signs of ataxia. These results suggest that the discrete trial shock titration paradigm is suitable for demonstration of the antinociceptive effects of opiate and certain nonopiate analgesics, but not nonsteroidal anti-inflammatory analgesics in the rhesus monkey. PMID:4057079

  2. Rhesus monkey sperm cryopreservation with TEST-yolk extender in the absence of permeable cryoprotectant.

    Science.gov (United States)

    Dong, Qiaoxiang; Correa, Liane M; VandeVoort, Catherine A

    2009-02-01

    Recently, there has been increased interest in ultra-rapid freezing with mammalian spermatozoa, especially for vitrification in the absence of cryoprotectants. Sperm cryopreservation in non-human primates has been successful, but the use of frozen-thawed sperm in standard artificial insemination (AI) remains difficult, and removal of permeable cryoprotectant may offer opportunities for increased AI success. The present study intended to explore the possibility of freezing rhesus monkey sperm in the absence of permeable cryoprotectants. Specifically, we evaluated various factors such as presence or absence of egg yolk, the percentage of egg yolk in the extenders, and the effect of cooling and thawing rate on the success of freezing without permeable cryoprotectants. Findings revealed that freezing with TEST in the absence of egg yolk offers little protection (range of 20-30% yielded the most motile sperm. Cooling at a slow rate (29 degrees C/min) reduced post-thaw motility significantly for samples frozen with TEST-yolk alone, but had no effect for controls in the presence of glycerol. Similarly, slow thawing in room temperature air is detrimental for freezing without permeable cryoprotectant (<2% motility). In addition to motility, the ability of sperm to capacitate based on an increase in intracellular calcium levels upon activation with cAMP and caffeine suggested no difference between fresh and frozen-thawed motile sperm, regardless of treatment. In summary, the present study demonstrates that ejaculated and epididymal sperm from rhesus monkeys can be cryopreserved with TEST-yolk (20%) in the absence of permeable cryoprotectant when samples were loaded in a standard 0.25-mL straw, cooled rapidly in liquid nitrogen vapor at 220 degrees C/min, and thawed rapidly in a 37 degrees C water bath. This study also represents the first success of freezing without permeable cryoprotectant in non-human primates. PMID:18992734

  3. Development of a flow feedback pulse duplicator system with rhesus monkey arterial input impedance characteristics

    Science.gov (United States)

    Schaub, J. D.; Koenig, S. C.; Schroeder, M. J.; Ewert, D. L.; Drew, G. A.; Swope, R. D.; Convertino, V. A. (Principal Investigator)

    1999-01-01

    An in vitro pulsatile pump flow system that is capable of producing physiologic pressures and flows in a mock circulatory system tuned to reproduce the first nine harmonics of the input impedance of a rhesus monkey was developed and tested. The system was created as a research tool for evaluating cardiovascular function and for the design, testing, and evaluation of electrical-mechanical cardiovascular models and chronically implanted sensors. The system possesses a computerized user interface for controlling a linear displacement pulsatile pump in a controlled flow loop format to emulate in vivo cardiovascular characteristics. Evaluation of the pump system consisted of comparing its aortic pressure and flow profiles with in vivo rhesus hemodynamic waveforms in the time and frequency domains. Comparison of aortic pressure and flow data between the pump system and in vivo data showed good agreement in the time and frequency domains, however, the pump system produced a larger pulse pressure. The pump system can be used for comparing cardiovascular parameters with predicted cardiovascular model values and for evaluating such items as vascular grafts, heart valves, biomaterials, and sensors. This article describes the development and evaluation of this feedback controlled cardiovascular dynamics simulation modeling system.

  4. Induced Neurocysticercosis in Rhesus Monkeys (Macaca mulatta Produces Clinical Signs and Lesions Similar to Natural Disease in Man

    Directory of Open Access Journals (Sweden)

    N. Chowdhury

    2014-01-01

    Full Text Available Neurocysticercosis is a serious endemic zoonosis resulting in increased cases of seizure and epilepsy in humans. The genesis of clinical manifestations of the disease through experimental animal models is poorly exploited. The monkeys may prove useful for the purpose due to their behavior and cognitive responses mimicking man. In this study, neurocysticercosis was induced in two rhesus monkeys each with 12,000 and 6,000 eggs, whereas three monkeys were given placebo. The monkeys given higher dose developed hyperexcitability, epileptic seizures, muscular tremors, digital cramps at 10 DPI, and finally paralysis of limbs, followed by death on 67 DPI, whereas the monkeys given lower dose showed delayed and milder clinical signs. On necropsy, all the infected monkeys showed numerous cysticerci in the brain. Histopathologically, heavily infected monkeys revealed liquefactive necrosis and formation of irregular cystic cavities lined by atrophied parenchymal septa with remnants of neuropil of the cerebrum. In contrast, the monkeys infected with lower dose showed formation of typical foreign body granulomas characterized by central liquefaction surrounded by chronic inflammatory response. It was concluded that the inflammatory and immune response exerted by the host against cysticerci, in turn, led to histopathological lesions and the resultant clinical signs thereof.

  5. Stability of the translocation frequency following whole-body irradiation measured in rhesus monkeys

    Science.gov (United States)

    Lucas, J. N.; Hill, F. S.; Burk, C. E.; Cox, A. B.; Straume, T.

    1996-01-01

    Chromosome translocations are persistent indicators of prior exposure to ionizing radiation and the development of 'chromosome painting' to efficiently detect translocations has resulted in a powerful biological dosimetry tool for radiation dose reconstruction. However, the actual stability of the translocation frequency with time after exposure must be measured before it can be used reliably to obtain doses for individuals exposed years or decades previously. Human chromosome painting probes were used here to measure reciprocal translocation frequencies in cells from two tissues of 8 rhesus monkeys (Macaca mulatta) irradiated almost three decades previously. Six of the monkeys were exposed in 1965 to whole-body (fully penetrating) radiation and two were unexposed controls. The primates were irradiated as juveniles to single doses of 0.56, 1.13, 2.00, or 2.25 Gy. Blood lymphocytes (and skin fibroblasts from one individual) were obtained for cytogenetic analysis in 1993, near the end of the animals' lifespans. Results show identical dose-response relationships 28 y after exposure in vivo and immediately after exposure in vitro. Because chromosome aberrations are induced with identical frequencies in vivo and in vitro, these results demonstrate that the translocation frequencies induced in 1965 have not changed significantly during the almost three decades since exposure. Finally, our emerging biodosimetry data for individual radiation workers are now confirming the utility of reciprocal translocations measured by FISH in radiation dose reconstruction.

  6. Head and neck resonance in a rhesus monkey - a comparison with results from a human model

    Science.gov (United States)

    Tinniswood, Adam; Gandhi, Om P.

    1999-03-01

    The use of primates for examining the effects of electromagnetic radiation on behavioural patterns is well established. Rats have also been used for this purpose. However, the monkey is of greater interest as its physiological make-up is somewhat closer to that of the human. Since the behavioural effects are likely to occur at lower field strengths for resonant absorption conditions for the head and neck, the need for determination of resonance frequencies for this region is obvious. Numerical techniques are ideal for the prediction of coupling to each of the organs, and accurate anatomically based models can be used to pinpoint the conditions for maximum absorption in the head in order to focus the experiments. In this paper we use two models, one of a human male and the other of a rhesus monkey, and find the mass-averaged power absorption spectra for both. The frequencies at which highest absorption (i.e. resonance) occurs in both the whole body and the head and neck region are determined. The results from these two models are compared for both E-polarization and k-polarization, and are shown to obey basic electromagnetic scaling principles.

  7. Head and neck resonance in a rhesus monkey - a comparison with results from a human model

    International Nuclear Information System (INIS)

    The use of primates for examining the effects of electromagnetic radiation on behavioural patterns is well established. Rats have also been used for this purpose. However, the monkey is of greater interest as its physiological make-up is somewhat closer to that of the human. Since the behavioural effects are likely to occur at lower field strengths for resonant absorption conditions for the head and neck, the need for determination of resonance frequencies for this region is obvious. Numerical techniques are ideal for the prediction of coupling to each of the organs, and accurate anatomically based models can be used to pinpoint the conditions for maximum absorption in the head in order to focus the experiments. In this paper we use two models, one of a human male and the other of a rhesus monkey, and find the mass-averaged power absorption spectra for both. The frequencies at which highest absorption (i.e. resonance) occurs in both the whole body and the head and neck region are determined. The results from these two models are compared for both E-polarization and k-polarization, and are shown to obey basic electromagnetic scaling principles. (author)

  8. Hydrolytic enzyme activity in rhesus monkey placenta during early gestational malaria : histochemical studies

    Directory of Open Access Journals (Sweden)

    Nishi Saxena & P.S.R. Murthy

    2005-12-01

    Full Text Available Background & objectives: Early gestational malaria is found to be more fatal than late gestationalinfection but the pathophysiology of early gestational placenta, the maternofoetal organ responsiblefor maintenance of pregnancy, remains unexplored. Present study dealing with hydrolytic enzymes inearly gestational placenta of rhesus monkeys during Plasmodium cynomolgi infection was anticipatedto provide a better insight into the functional impairment of this organ during early gestationalmaternal malaria.Methods: Experimental monkeys (Macaca multtta at 2–2½ months of pregnancy were inoculatedwith P. cynomolgi bastianelli. After attaining first peak of parasitaemia the animals were anesthetisedand placentae were collected for histochemical studies. The snap-frozen, cryostat sections weresubjected to histochemical reactions for acid phosphatase and alkaline phosphatase.Results: The placental syncytiotrophoblast showed a loss in alkaline phosphatase activity, while thetrophoblast layers and phagocytic cells of the maternal blood showed increased acid phosphataseactivity during early gestational malarial infection. Morphological damage to the placental tissuewhenever occurred was associated with altered Alk pase activity.Interpretation & conclusion: The altered distribution of Ac pase and Alk pase in malaria infectedearly gestational placenta has been discussed in the light of placental function. It could be concludedby present studies that these malaria induced changes in hydrolytic enzyme activities in monkeyplacenta have a direct bearing on functional and morphological integrity of the placental tissue.These changes are apparently responsible for early gestational foetal death and abortions as reportedin literature

  9. Delay discounting of the μ-opioid receptor agonist remifentanil in rhesus monkeys.

    Science.gov (United States)

    Maguire, David R; Gerak, Lisa R; France, Charles P

    2016-04-01

    Although increased impulsivity (delay discounting) is an important risk factor for drug abuse, the impact of delay on drug taking has received relatively little attention. This study examined delay discounting of the μ-opioid receptor agonist remifentanil in rhesus monkeys (n=4) responding for intravenous infusions under a concurrent choice procedure. Dose-effect curves for remifentanil were determined by varying the dose available on one lever (0.001-0.32 μg/kg/infusion) while keeping the dose available on the other lever (0.1 μg/kg/infusion) the same. Dose-effect curves were determined when both infusions were delivered immediately and when delivery of the fixed dose was delayed (15-180 s). When both doses of remifentanil were delivered immediately, monkeys chose the large dose. Delaying delivery of the fixed dose reduced choice of that dose and increased choice of small immediately available doses. Extending previous studies, these results show that the effects of delay on choice between two doses of a μ-opioid receptor agonist are consistent with hyperbolic discounting. Delaying delivery of a preferred reinforcer (e.g. large dose of drug) reduces its effectiveness and increases the effectiveness of small immediately available doses. This effect of delay, particularly on drug self-administration, might contribute to drug abuse. PMID:26397761

  10. Estrogen formation and binding in the cerebral cortex of the developing rhesus monkey

    International Nuclear Information System (INIS)

    These studies were undertaken to determine whether estrogen receptors and the microsomal enzyme system called the aromatase complex, which is responsible for conversion of androgen to estrogen, are present in the brain of the rhesus monkey during perinatal life. Four monkeys (three females-one fetus removed on day 153 of gestation and two infants, 5 and 6 days postnatal-and 1 male, 2 days postnatal) were studied. Cytosol estrogen receptors were detected in all brain regions examined. The apparent equilibrium dissociations constants for reaction of these sites with 3H-moxestrol were similar to those for uterine and pituitary cytosol estrogen receptors (0.3-1.1 nM). Within the brain, highest levels of binding were observed in the hypothalamus-preoptic area, with fairly even, lower concentrations throughout the cortical structures. Aromatase complex activity was detected in the majority of the tissue specimens. The highest levels of estrogen formation were observed in the hypothalamus. Among the cortical samples, the highest levels of aromatase complex activity were found in regions of the association cortex. The lowest levels of aromatase activity were found in the somatosensory and motor cortices of the postnatal animals. These results suggest that locally-formed estrogen may be involved in the effects of circulating androgens on the developing primate neocortex

  11. Primary pulmonary sarcoma in a rhesus monkey after inhalation of plutonium dioxide

    International Nuclear Information System (INIS)

    A pulmonary fibrosarcoma of bronchial origin was discovered in a Rhesus monkey that died of pulmonary fibrosis 9 years after inhalation of plutonium-239 dioxide and with a radiation dose to lung of 1400 rad (14 Gy). It grew around the major bronchus of the right cardiac lung lobe and extended into the bronchial lumen and into surrounding pulmonary parenchyma. It also readily invaded muscular pulmonary arteries, resulting in infarction and scarring in the right cardiac lobe. Despite this aggressive growth, the tumor did not metastasize. The primary cause of death was severe pulmonary fibrosis involving the alveolar septa and and perivascular and peribronchial interstitium. Bullous or pericitrical emphysema was prominent. The initial lung burden of plutonium in this monkey was 270 nCi (10 kBq) which is equivalent to approximately 500 times the maximum permissible lung burden for man on a radioactivity per unit body weight basis. The time-dose relationship for survival is consistent with that of dogs and baboons that inhaled plutonium dioxide and died with lung tumors

  12. Pulmonary sarcoma in a Rhesus monkey after inhalation of plutonium dioxide

    International Nuclear Information System (INIS)

    A pulmonary fibrosarcoma of bronchial origin was discovered in a Rhesus monkey that died of pulmonary fibrosis nine years after inhalation of plutonium-239 dioxide. The tumor was well delineated but not encapsulated. It grew around the major bronchus of the right cardiac lung lobe and extended into the bronchial lumen and into surrounding pulmonary parenchyma. It also readily invaded muscular arteries, resulting in infarction and scarring in the right cardiac lobe. Despite this aggressive growth, the tumor did not metastasize. The primary cause of death was severe pulmonary fibrosis involving the alveolar septa and perivascular and peribronchial interstitium. Bullous or pericitrical emphysema was prominent. The initial lung burden of plutonium in this monkey was 270 nCi. This burden is equivalent to approx. 500 times the maximum permissible lung burden for man. The time-dose relationship for survival is consistent with that of dogs and baboons that inhaled plutonium dioxide, thus further strengthening the extrapolation of plutonium toxicity data from one species to another. 4 references, 3 figures, 1 table

  13. Effect of restricted maternal zinc intake on zinc absorption in infant rhesus monkeys

    International Nuclear Information System (INIS)

    One compensatory mechanism for marginal Zn intake may be enhanced absorption of Zn. While there is some experimental evidence to support this hypothesis from rodent models, there are few data from higher mammalian species. Such a compensatory mechanism of enhanced Zn absorption could be of value to the neonate, as poor Zn nutriture during early life has severe consequences on growth and development. The authors have investigated the absorption of Zn by infant Rhesus monkeys born to control and Zn-restricted mothers. Fasted infant monkeys (100 d) from mothers fed a 100 or 4 ppm Zn diet were intubated with an infant formula containing Zn-65. Whole body radioactivity was counted immediately after intubation and on days 10 and 17 post-intubation. Day 10 data were used to calculate apparent absorption values. Regardless of dietary group, apparent Zn absorption as high, ranging from 30-60% of the dose fed. While there was not a marked difference between the two groups in the groups in the dose absorbed, an inverse correlation was noted between infant body weight and Zn absorption. An inverse correlation was found for plasma Zn concentration and apparent Zn absorption. These results suggest that body weight and plasma Zn level, as related to Zn status and growth rate, may be predictors of Zn absorption

  14. Epigenetic mechanism underlying the development of polycystic ovary syndrome (PCOS-like phenotypes in prenatally androgenized rhesus monkeys.

    Directory of Open Access Journals (Sweden)

    Ning Xu

    Full Text Available The pathogenesis of polycystic ovary syndrome (PCOS is poorly understood. PCOS-like phenotypes are produced by prenatal androgenization (PA of female rhesus monkeys. We hypothesize that perturbation of the epigenome, through altered DNA methylation, is one of the mechanisms whereby PA reprograms monkeys to develop PCOS. Infant and adult visceral adipose tissues (VAT harvested from 15 PA and 10 control monkeys were studied. Bisulfite treated samples were subjected to genome-wide CpG methylation analysis, designed to simultaneously measure methylation levels at 27,578 CpG sites. Analysis was carried out using Bayesian Classification with Singular Value Decomposition (BCSVD, testing all probes simultaneously in a single test. Stringent criteria were then applied to filter out invalid probes due to sequence dissimilarities between human probes and monkey DNA, and then mapped to the rhesus genome. This yielded differentially methylated loci between PA and control monkeys, 163 in infant VAT, and 325 in adult VAT (BCSVD P<0.05. Among these two sets of genes, we identified several significant pathways, including the antiproliferative role of TOB in T cell signaling and transforming growth factor-β (TGF-β signaling. Our results suggest PA may modify DNA methylation patterns in both infant and adult VAT. This pilot study suggests that excess fetal androgen exposure in female nonhuman primates may predispose to PCOS via alteration of the epigenome, providing a novel avenue to understand PCOS in humans.

  15. Mucinous gastric hyperplasia in a colony of rhesus monkeys (Macaca mulatta) induced by polychlorinated biphenyl (Aroclor 1254)

    Energy Technology Data Exchange (ETDEWEB)

    Geistfeld, J.G.; Bond, M.G.; Bullock, B.C.; Varian, M.C.

    1982-02-01

    Since 1971, 45 of 259 male rhesus monkeys housed in a primate building have died of a chronic and progressive disease characterized by diarrhea, dehydration, weakness, gingivitis, emaciation, and alopecia. The principal necropsy finding in these monkeys, and in eight others killed for experimental purposes, was hypertrophic and hyperplastic mucinous gastropathy involving both the mucosa and submucosa. The toxic agent involved was identified as the polychlorinated biphenyl (PCB), Aroclor 1254. The suspected source of the toxic agent was a concrete sealer used during building construction.

  16. Toxicological consequences of feeding PCB congeners to infant rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) monkeys.

    Science.gov (United States)

    Arnold, D L; Bryce, F; Mes, J; Tryphonas, H; Hayward, S; Malcolm, S

    1999-01-01

    In a study designed to minimize interspecies extrapolation of toxicological data, nine rhesus (Macaca mulatta) and 15 cynomolgus (M. fascicularis) day-old infant monkeys were separated from their dams following parturition and hand-reared using a liquid non-human primate formulation. The infants were randomly divided into a control and a treated group which received a mixture of polychlorinated biphenyl (PCB) congeners analogous to those found in breast milk from Canadian women. The concentration of congeners in the dosing media resulted in each infant receiving a total of 7.5 microg PCB congeners/kg body weight/day. The congeners were added either to the liquid formulation or to corn oil and administered to the back of the monkey's mouth for 20 weeks. Monthly blood and adipose specimens were obtained during the dosing period and then periodically until the monkey was necropsied or taken off test (minimum of 66 weeks on test) for congener analysis. Parameters such as body weight, formula consumption, tooth eruption, somatic measurements, haematology and serum biochemistry were monitored throughout the study. In addition, a qualitative evaluation of the absorption and depletion of the various congeners was undertaken as was an immunological evaluation. For the monitored parameters, very few differences were found to be statistically significant. For the immunological parameters, the only statistically differences found were a reduction over time for immunoglobulins M and G antibodies to sheep red blood cells (cyno, P = 0.025; rhesus, P = 0.002) and a treatment-related reduction in the levels of the HLA-DR cell surface marker (mean percent, P = 0.016; absolute levels, P = 0.027). There were some qualitative differences regarding absorption and depletion rates for the various congeners, but it could not be definitely ascertained whether these differences were due to species differences or dosing mode. However, statistically significant differences were found for

  17. Power spectrum analysis of myometrial electromyogram and intrauterine pressure changes in the pregnant rhesus monkey in late gestation.

    Science.gov (United States)

    Hsu, H W; Figueroa, J P; Honnebier, M B; Wentworth, R; Nathanielsz, P W

    1989-08-01

    Various methods have been used to quantify myometrial activity in the pregnant rhesus monkey during the last third of gestation. A precise definition of activity must retain the characteristics of epoch duration, amplitude, and the repetitive frequencies of active epochs. We used Fast Fourier Transform and power spectrum analysis to determine whether the patterns of myometrial contractility consist predominantly of contractions or contractures. This analysis allows quantification of activity represented by each of these patterns of activity. We applied these methods to myometrial electromyogram and intrauterine pressure recordings in pregnant rhesus monkeys to characterize the changes in myometrial activity that occur after surgery, after intravenous indomethacin administration, and when food is withdrawn for 48 hours. We conclude that changes in the frequency pattern of myometrial activity provide important information in relation to labor and delivery contractions. PMID:2764063

  18. Biological characteristics of different epidemic enterovirus 71 strains and their pathogeneses in neonatal mice and rhesus monkeys.

    Science.gov (United States)

    Zhongping, Xie; Hua, Li; Ting, Yang; Zhengling, Liu; Min, Feng; Tianhong, Xie; Runxiang, Long; Dong, Shen; Guangju, Jiang; Lei, Yue; Rong, Yang; Fangyu, Luo; Qihan, Li

    2016-02-01

    Hand, foot and mouth disease (HFMD) has been prevalent in China since 2008. Enterovirus 71 (EV71) is a common causative agent of HFMD, and various strains of EV71 are prevalent worldwide. The EV71C4 subgenotype is the most endemic strain in China. However, few studies investigating the biological characteristics and pathogeneses of different C4 strains have been reported. Therefore, the current study investigated 19 clinical EV71 strains in neonatal ICR mice and neonatal rhesus monkeys by comparing pathogenicity; the virulence of different viral passages, dosages, and routes of infection; and the effects produced by subject animal age. These 19 clinical EV71 strains, which were of the same subtype, displayed varying pathogenic effects. Three strains (HE31, 231 and 262) induced limb paralysis in neonatal ICR mice. In addition, the degree of virulence was largely dependent upon the dose, route of infection, and number of passages of the challenge virus, as well as the ages of the infected animals. The present study provides valuable basic data to enable further research into EV71 pathogenesis and to facilitate the development of new drugs and vaccines. PMID:26555165

  19. Environmental Context Differentially Affects Behavioral, Leukocyte, Cortisol and Interleukin-6 Responses to Low Doses of Endotoxin in the Rhesus Monkey

    OpenAIRE

    Willette, Auriel A.; Lubach, Gabriele R.; Coe, Christopher L.

    2007-01-01

    Bacterial infections and proinflammatory cytokines induce behavioral and physiological responses associated with withdrawal and sickness behavior. These effects in rodents are often exacerbated by stressful environmental contexts. To model this synergistic effect of arousal and stress, low doses of lipopolysaccharide (LPS), 4 or 40 ng/kg, were administered to rhesus monkeys in different environmental contexts. Activity, emotional and social behaviors, cortisol, interleukin-6 (IL-6), and perip...

  20. Dose-response studies on the spermatogonial stem cells of the rhesus monkey (Macaca mulatta) after X irradiation

    International Nuclear Information System (INIS)

    Studies of the dose response of the spermatogonial stem cells in the rhesus monkey were performed at intervals of 130 and 160 days after graded doses of X irradiation. The D0 of the spermatogonial stem cells was established using the total numbers of the type A spermatogonia that were present at 130 and 160 days after irradiation and was found to be 1.07 Gy; the 95% confidence interval was 0.90-1.34 Gy

  1. Detection and cellular localization of lead by electron probe analysis in the diagnosis of suspected lead poisoning in rhesus monkeys

    International Nuclear Information System (INIS)

    Lead poisoning of unknown source was diagnosed histologically in 2 rhesus monkeys (Macaca mulatta) by finding acid-fast intranuclear inclusion bodies in the epithelial cells of renal cortical tubules. The presence of lead in the inclusions was determined by scanning electron microscopy/energy dispersive x-ray analysis using sections from paraffin embedded tissues. This observation indicates the usefulness of this technique for the detection and cellular localization of lead in tissues, even from archival material

  2. Pre-clinical toxicity & immunobiological evaluation of DNA rabies vaccine & combination rabies vaccine in rhesus monkeys (Macaca mulatta)

    OpenAIRE

    Kumar, Dinesh B; Kumar, Uday P; Krishna, Prasanna T; Kalyanasundaram, S.; Suresh, P; Jagadeesan, V; S. Hariharan; Naidu, Nadamuni A; Krishnaswamy, Kamala; Rangarajan, PN; Srinivasan, VA; Reddy, GS; Sesikeran, B.

    2013-01-01

    Background & objectives: Pre-clinical toxicology evaluation of biotechnology products is a challenge to the toxicologist. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed recombinant DNA anti-rabies vaccine DRV (100 mu g)] and combination rabies vaccine CRV (100 mu g DRV and 1.25 IU of cell culture-derived inactivated rabies virus vaccine)], which are intended for clinical use by intramuscular route in Rhesus monkeys. Methods: As per t...

  3. Disposition of nafarelin acetate, a potent agonist of luteinizing hormone-releasing hormone, in rats and rhesus monkeys

    International Nuclear Information System (INIS)

    Nafarelin acetate, [6-(3-(2-naphthyl)-D-Ala)]-luteinizing hormone-releasing hormone (LHRH), is a synthetic LHRH agonist. In the suppression of estrus in female rats, nafarelin acetate was about 200 times as potent as LHRH. The authors have studied the distribution and excretion of radiolabeled nafarelin acetate administered iv to rats and rhesus monkeys and have also compared the pharmacokinetics of nafarelin acetate to LHRH in these two species. Distribution of a single 100-micrograms dose [14C]nafarelin acetate into tissues in male rats was rapid and of the 13 tissues assayed, highest concentrations of radioactivity were observed in the kidneys, liver, and intestines. The urine to feces ratio of nafarelin-associated 14C was 4:1 in rhesus monkeys and 1:3 in rats. Nafarelin acetate and LHRH given iv to female rhesus monkeys in approximately equimolar doses had terminal plasma t1/2 values of 120 min and 33 min, and systemic clearance values of 2.7 ml/min/kg and 31.4 ml/min/kg, respectively. In female rats, the plasma t1/2 was 33.6 min for nafarelin acetate and 6.7 min for LHRH, and the systemic clearance values for nafarelin acetate and LHRH were 12.0 ml/min/kg and 57.6 ml/min/kg, respectively, after approximately equimolar doses

  4. Association of activating KIR copy number variation of NK cells with containment of SIV replication in rhesus monkeys.

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    Ina Hellmann

    2011-12-01

    Full Text Available While the contribution of CD8⁺ cytotoxic T lymphocytes to early containment of HIV-1 spread is well established, a role for NK cells in controlling HIV-1 replication during primary infection has been uncertain. The highly polymorphic family of KIR molecules expressed on NK cells can inhibit or activate these effector cells and might therefore modulate their activity against HIV-1-infected cells. In the present study, we investigated copy number variation in KIR3DH loci encoding the only activating KIR receptor family in rhesus monkeys and its effect on simian immunodeficiency virus (SIV replication during primary infection in rhesus monkeys. We observed an association between copy numbers of KIR3DH genes and control of SIV replication in Mamu-A*01⁻ rhesus monkeys that express restrictive TRIM5 alleles. These findings provide further evidence for an association between NK cells and the early containment of SIV replication, and underscore the potential importance of activating KIRs in stimulating NK cell responses to control SIV spread.

  5. Changes of dopamine transporter function in striatum during acute morphine addiction and its abstinence in rhesus monkey

    Institute of Scientific and Technical Information of China (English)

    XIAO Zhuang-wei; CAO Chu-yu; WANG Zhao-xin; LI Jun-xiong; LIAO Hai-yong; ZHANG Xue-xin

    2006-01-01

    Background Although dopamine transporter (DAT) is essential for addiction, the effect of additive drugs on DAT function is still controversial, especially for opiates. We investigated the functional changes of dopamine transporter in striatum of rhesus monkeys during acute morphine injection and its abstinence.Methods Four rhesus monkeys, 6 to 9 years old, two male and two female, were examined for 12 days. Single photon emission computed tomography (SPECT) was performed with 99Tcm-TRODAT-1 as the radiopharmaceutical dopamine transporter agent during different stages of acute morphine injection and its abstinence. The ratios of SPECT signal between striatum and cerebellum (ST/CB) were calculated.Results The ST/CB ratio declined significantly on the first day of morphine injection and continued declining with more morphine injections. After abstinence, the ratio increased with time, but was still significantly lower on the 5th day of abstinence than the normal level.Conclusions In rhesus monkey, acute morphine injection has both rapid and lasting effects on DAT by downregulating its function. The decline was partially reversible following morphine abstinence. The results suggest that striatum is one effective target of morphine and that the DAT function in striatum is one indicator for morphine addiction.

  6. Global gene expression analysis of peripheral blood mononuclear cells in rhesus monkey infants with CA16 infection-induced HFMD.

    Science.gov (United States)

    Song, Jie; Hu, Yajie; Hu, Yunguang; Wang, Jingjing; Zhang, Xiaolong; Wang, Lichun; Guo, Lei; Wang, Yancui; Ning, Ruotong; Liao, Yun; Zhang, Ying; Zheng, Huiwen; Shi, Haijing; He, Zhanlong; Li, Qihan; Liu, Longding

    2016-03-01

    Coxsackievirus A16 (CA16) is a dominant pathogen that results in hand, foot, and mouth disease and causes outbreaks worldwide, particularly in the Asia-Pacific region. However, the underlying molecular mechanisms remain unclear. Our previous study has demonstrated that the basic CA16 pathogenic process was successfully mimicked in rhesus monkey infant. The present study focused on the global gene expression changes in peripheral blood mononuclear cells of rhesus monkey infants with hand, foot, and mouth disease induced by CA16 infection at different time points. Genome-wide expression analysis was performed with Agilent whole-genome microarrays and established bioinformatics tools. Nine hundred and forty-eight significant differentially expressed genes that were associated with 5 gene ontology categories, including cell communication, cell cycle, immune system process, regulation of transcription and metabolic process were identified. Subsequently, the mapping of genes related to the immune system process by PANTHER pathway analysis revealed the predominance of inflammation mediated by chemokine and cytokine signaling pathways and the interleukin signaling pathway. Ultimately, co-expressed genes and their networks were analyzed. The results revealed the gene expression profile of the immune system in response to CA16 in rhesus monkey infants and suggested that such an immune response was generated as a result of the positive mobilization of the immune system. This initial microarray study will provide insights into the molecular mechanism of CA16 infection and will facilitate the identification of biomarkers for the evaluation of vaccines against this virus. PMID:26775814

  7. Radical curative efficacy of tafenoquine combination regimens in Plasmodium cynomolgi-infected Rhesus monkeys (Macaca mulatta

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    Kenworthy David

    2011-07-01

    Full Text Available Abstract Background Tafenoquine is an 8-aminoquinoline being developed for radical cure (blood and liver stage elimination of Plasmodium vivax. During monotherapy treatment, the compound exhibits slow parasite and fever clearance times, and toxicity in glucose-6-phosphate dehydrogenase (G6PD deficiency is a concern. Combination with other antimalarials may mitigate these concerns. Methods In 2005, the radical curative efficacy of tafenoquine combinations was investigated in Plasmodium cynomolgi-infected naïve Indian-origin Rhesus monkeys. In the first cohort, groups of two monkeys were treated with a three-day regimen of tafenoquine at different doses alone and in combination with a three-day chloroquine regimen to determine the minimum curative dose (MCD. In the second cohort, the radical curative efficacy of a single-day regimen of tafenoquine-mefloquine was compared to that of two three-day regimens comprising tafenoquine at its MCD with chloroquine or artemether-lumefantrine in groups of six monkeys. In a final cohort, the efficacy of the MCD of tafenoquine against hypnozoites alone and in combination with chloroquine was investigated in groups of six monkeys after quinine pre-treatment to eliminate asexual parasites. Plasma tafenoquine, chloroquine and desethylchloroquine concentrations were determined by LC-MS in order to compare doses of the drugs to those used clinically in humans. Results The total MCD of tafenoquine required in combination regimens for radical cure was ten-fold lower (1.8 mg/kg versus 18 mg/kg than for monotherapy. This regimen (1.8 mg/kg was equally efficacious as monotherapy or in combination with chloroquine after quinine pre-treatment to eliminate asexual stages. The same dose of (1.8 mg/kg was radically curative in combination with artemether-lumefantrine. Tafenoquine was also radically curative when combined with mefloquine. The MCD of tafenoquine monotherapy for radical cure (18 mg/kg appears to be biologically

  8. Emergence and evolution of inter-specific segregating retrocopies in cynomolgus monkey (Macaca fascicularis) and rhesus macaque (Macaca mulatta)

    Science.gov (United States)

    Zhang, Xu; Zhang, Qu; Su, Bing

    2016-01-01

    Retroposition is an RNA-mediated mechanism to generate gene duplication, and is believed to play an important role in genome evolution and phenotypic adaptation in various species including primates. Previous studies suggested an elevated rate of recent retroposition in the rhesus macaque genome. To better understand the impact of retroposition on macaque species which have undergone an adaptive radiation approximately 3–6 million years ago, we developed a bioinformatics pipeline to identify recently derived retrocopies in cynomolgus monkeys. As a result, we identified seven experimentally validated young retrocopies, all of which are polymorphic in cynomolgus monkeys. Unexpectedly, five of them are also present in rhesus monkeys and are still segregating. Molecular evolutionary analysis indicates that the observed inter-specific polymorphism is attribute to ancestral polymorphism. Further population genetics analysis provided strong evidence of balancing selection on at least one case (Crab-eating monkey retrocopy 6, or CER6) in both species. CER6 is in adjacent with an immunoglobulin related gene and may be involved in host-pathogen interaction, a well-known target of balancing selection. Altogether, our data support that retroposition is an important force to shape genome evolution and species adaptation. PMID:27600022

  9. Production of rhesus monkey cloned embryos expressing monomeric red fluorescent protein by interspecies somatic cell nuclear transfer

    International Nuclear Information System (INIS)

    Highlights: • Rhesus monkey cells were electroporated with a plasmid containing mRFP1, and an mRFP1-expressing cell line was generated. • For the first time, mRFP1-expressing rhesus monkey cells were used as donor cells for iSCNT. • The effect of VPA on the development of embryos cloned using iSCNT was determined. - Abstract: Interspecies somatic cell nuclear transfer (iSCNT) is a promising method to clone endangered animals from which oocytes are difficult to obtain. Monomeric red fluorescent protein 1 (mRFP1) is an excellent selection marker for transgenically modified cloned embryos during somatic cell nuclear transfer (SCNT). In this study, mRFP-expressing rhesus monkey cells or porcine cells were transferred into enucleated porcine oocytes to generate iSCNT and SCNT embryos, respectively. The development of these embryos was studied in vitro. The percentage of embryos that underwent cleavage did not significantly differ between iSCNT and SCNT embryos (P > 0.05; 71.53% vs. 80.30%). However, significantly fewer iSCNT embryos than SCNT embryos reached the blastocyst stage (2.04% vs. 10.19%, P < 0.05). Valproic acid was used in an attempt to increase the percentage of iSCNT embryos that developed to the blastocyst stage. However, the percentages of embryos that underwent cleavage and reached the blastocyst stage were similar between untreated iSCNT embryos and iSCNT embryos treated with 2 mM valproic acid for 24 h (72.12% vs. 70.83% and 2.67% vs. 2.35%, respectively). These data suggest that porcine-rhesus monkey interspecies embryos can be generated that efficiently express mRFP1. However, a significantly lower proportion of iSCNT embryos than SCNT embryos reach the blastocyst stage. Valproic acid does not increase the percentage of porcine-rhesus monkey iSCNT embryos that reach the blastocyst stage. The mechanisms underling nuclear reprogramming and epigenetic modifications in iSCNT need to be investigated further

  10. Production of rhesus monkey cloned embryos expressing monomeric red fluorescent protein by interspecies somatic cell nuclear transfer

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Hai-Ying; Kang, Jin-Dan; Li, Suo; Jin, Jun-Xue; Hong, Yu; Jin, Long; Guo, Qing; Gao, Qing-Shan; Yan, Chang-Guo; Yin, Xi-Jun, E-mail: yinxj33@msn.com

    2014-02-21

    Highlights: • Rhesus monkey cells were electroporated with a plasmid containing mRFP1, and an mRFP1-expressing cell line was generated. • For the first time, mRFP1-expressing rhesus monkey cells were used as donor cells for iSCNT. • The effect of VPA on the development of embryos cloned using iSCNT was determined. - Abstract: Interspecies somatic cell nuclear transfer (iSCNT) is a promising method to clone endangered animals from which oocytes are difficult to obtain. Monomeric red fluorescent protein 1 (mRFP1) is an excellent selection marker for transgenically modified cloned embryos during somatic cell nuclear transfer (SCNT). In this study, mRFP-expressing rhesus monkey cells or porcine cells were transferred into enucleated porcine oocytes to generate iSCNT and SCNT embryos, respectively. The development of these embryos was studied in vitro. The percentage of embryos that underwent cleavage did not significantly differ between iSCNT and SCNT embryos (P > 0.05; 71.53% vs. 80.30%). However, significantly fewer iSCNT embryos than SCNT embryos reached the blastocyst stage (2.04% vs. 10.19%, P < 0.05). Valproic acid was used in an attempt to increase the percentage of iSCNT embryos that developed to the blastocyst stage. However, the percentages of embryos that underwent cleavage and reached the blastocyst stage were similar between untreated iSCNT embryos and iSCNT embryos treated with 2 mM valproic acid for 24 h (72.12% vs. 70.83% and 2.67% vs. 2.35%, respectively). These data suggest that porcine-rhesus monkey interspecies embryos can be generated that efficiently express mRFP1. However, a significantly lower proportion of iSCNT embryos than SCNT embryos reach the blastocyst stage. Valproic acid does not increase the percentage of porcine-rhesus monkey iSCNT embryos that reach the blastocyst stage. The mechanisms underling nuclear reprogramming and epigenetic modifications in iSCNT need to be investigated further.

  11. Radioprotective effects of CBLB502 on γ-radiated Rhesus monkey

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    Xing SHEN

    2015-06-01

    Full Text Available Objective A Rhesus monkey model was employed to study the radioprotective effects of a Toll-like receptor 5 agonist, CBLB502, against 7.0Gy whole-body irradiation of 60Co gamma-rays. Methods Thirty animals were assigned to a placebo treatment group, a WR-2721 positive control group, and three CBLB502 treatment groups (n=6 animals/group. Each animal was irradiated with 7.0Gy 60Co γ and given CBLB502 at 2.5, 10 and 40μg/kg, respectively in treatment groups, or WR-2721 at 30mg/kg, or physiological saline 0.3ml/kg for the placebo treatment group. The treatment was given once by intramuscular injection 30 min before irradiation. All irradiated animals received symptomatic treatment based on same guidelines. General observation, peripheral blood tests, hemopoietic progenitor cell colony-counting, and histopathological examination were performed. Results We found that 10 or 40μg/kg CBLB502 treatment resulted in 100% survival, while the survival rate was 33% in placebo treatment group. Hematopoietic recovery in the WR-2721 treatment group was marginally superior to the irradiation control group. Nadirs of peripheral white cell and platelet counts of animals treated with 40μg/kg of CBLB502 were significantly higher than those of the placebo treatment group (P<0.05. CBLB502 at 40μg/kg also gave a shortened duration of low platelet count, earlier recovery time, reduced the amount of blood transfusion and damage to the bone marrow and intestine. Conclusion All Rhesus monkeys irradiated with 7.0Gy 60Co γ-rays would suffer from severe acute radiation sickness of hematopoietic system. CBLB502 at 40μg/kg is radioprotective in this model and a single intramuscular injection of CBLB502 in a dose of 40μg/kg 30min before irradiation gives better radioprotective effects than WR-2721. DOI: 10.11855/j.issn.0577-7402.2015.04.07

  12. Systemic administration of 6-OHDA to rhesus monkeys upregulates HLA-DR expression in brain microvasculature

    Directory of Open Access Journals (Sweden)

    Joers V

    2014-09-01

    Full Text Available Valerie Joers,1,2 Scott Vermilyea,1,2 Kristine Dilley,1 Marina E Emborg1–3 1Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, 2Neuroscience Training Program, 3Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA Background: We recently developed a nonhuman primate model of cardiac dysautonomia by systemic dosing of the catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA. The aim of this study was to assess whether systemic 6-OHDA affects the central nervous system of nonhuman primates, in particular the dopaminergic nigrostriatal system. Methods: Brain sections from adult rhesus monkeys that received systemic 6-OHDA (50 mg/kg intravenously; n=5 and were necropsied 3 months later, as well as normal controls (n=5 were used in this study. Tissue was cut frozen at 40 µm on a sliding microtome, processed for immunohistochemistry, and blindly evaluated. Results: Neither the optical density of tyrosine hydroxylase immunoreactivity (TH-ir; a dopaminergic neuronal marker in the caudate and putamen nucleus nor the TH-ir cell number and volume in the substantia nigra showed significant differences between groups. Yet within groups, statistical analysis revealed significant individual differences in the 6-OHDA-treated group, with two animals showing a lower cell count and volume. Optical density quantification of α-synuclein-ir in the substantia nigra did not show differences between groups. As α-synuclein intracellular distribution was noted to vary between animals, it was further evaluated with a semiquantitative scale. A greater intensity and presence of α-synuclein-positive nigral cell bodies was associated with larger TH-positive nigral cell volumes. Increased human leukocyte antigen (HLA-DR; a microglial marker expression was observed in 6-OHDA-treated animals compared with controls. HLA-DR-ir was primarily localized in endothelial cells and perivascular spaces throughout

  13. Preclinical evaluation of a urokinase plasminogen activator receptor-targeted nanoprobe in rhesus monkeys

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    Chen Y

    2015-10-01

    Full Text Available Yushu Chen,1 Li Gong,2 Ning Gao,3 Jichun Liao,1 Jiayu Sun,1 Yuqing Wang,1 Lei Wang,1 Pengjin Zhu,1 Qing Fan,1 Yongqiang Andrew Wang,4 Wen Zeng,2 Hui Mao,3 Lily Yang,5 Fabao Gao11Molecular Imaging Center, Department of Radiology, West China Hospital, Sichuan University, Chengdu, 2Sichuan Primed Bio-Tech Group Co, Ltd, Chengdu, People’s Republic of China; 3Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, 4Ocean NanoTech, LLC, San Diego, CA, 5Department of Surgery, Emory University School of Medicine, Atlanta, GA, USAPurpose: To translate a recombinant peptide containing the amino-terminal fragment (ATF of urokinase plasminogen activator receptor-targeted magnetic iron oxide (IO nanoparticles (uPAR-targeted human ATF-IONPs into clinical applications, we conducted a pilot study to evaluate the toxicity and pharmacokinetics of this nanoparticle in normal rhesus monkeys.Methods: We assessed the changes in the following: magnetic resonance imaging (MRI signals from pretreatment stage to 14 days posttreatment, serum iron concentrations from 5 minutes posttreatment to 12 weeks posttreatment, routine blood examination and serum chemistry analysis results from pretreatment stage to 12 weeks after administration, and results of staining of the liver with Perls’ Prussian Blue and hematoxylin–eosin at 24 hours and 3 months posttreatment in two rhesus monkeys following an intravenous administration of the targeted nanoparticles either with a polyethylene glycol (ATF-PEG-IONP or without a PEG (ATF-IONP coating.Results: The levels of alkaline phosphatase, alanine transaminase, and direct bilirubin in the two monkeys increased immediately after the administration of the IONPs but returned to normal within 20 days and stayed within the normal reference range 3 months after the injection. The creatinine levels of the two monkeys stayed within the normal range during the study. In addition, red blood cells

  14. Molecularly engineered live-attenuated chimeric West Nile/dengue virus vaccines protect rhesus monkeys from West Nile virus

    International Nuclear Information System (INIS)

    Two molecularly engineered, live-attenuated West Nile virus (WN) vaccine candidates were highly attenuated and protective in rhesus monkeys. The vaccine candidates are chimeric viruses (designated WN/DEN4) bearing the membrane precursor and envelope protein genes of WN on a backbone of dengue 4 virus (DEN4) with or without a deletion of 30 nucleotides (Δ30) in the 3' noncoding region of DEN4. Viremia in WN/DEN4- infected monkeys was reduced 100-fold compared to that in WN- or DEN4-infected monkeys. WN/DEN4-3'Δ30 did not cause detectable viremia, indicating that it is even more attenuated for monkeys. These findings indicate that chimerization itself and the presence of the Δ30 mutation independently contribute to the attenuation phenotype for nonhuman primates. Despite their high level of attenuation in monkeys, the chimeras induced a moderate-to-high titer of neutralizing antibodies and prevented viremia in monkeys challenged with WN. The more attenuated vaccine candidate, WN/DEN4-3'Δ30, will be evaluated first in our initial clinical studies

  15. Sympathoadrenal responses to cold and ketamine anesthesia in the rhesus monkey.

    Science.gov (United States)

    Kolka, M A; Elizondo, R S; Weinberg, R P

    1983-04-01

    The effect of cold exposure on the sympathoadrenal system in primates was studied with and without ketamine anesthesia in eight adult rhesus monkeys. Each monkey was placed in a primate chair at a thermoneutral temperature (25 degrees C) for 1 h (control) followed by cold exposure (12 degrees C) for 3 h or placed in a circulating water bath (28 degrees C) to induce a decrease in core temperature (Tre) to 35 and 33 degrees C. Plasma catecholamines were analyzed by high-pressure liquid chromatography with electrochemical detection (60-65% recovery, coefficient of variation = 15%). The 3-h cold exposure was associated with a 175% increase above control levels of norepinephrine (NE) and a 100% increase in epinephrine (E). Decreases were evident in Tre (0.5 degree C), mean skin temperature (Tsk, 5.5 degrees C), and mean body temperature (Tb, 2.0 degrees C). Continuous infusion of ketamine (0.65 mg . kg-1 . min-1) resulted in no change in the plasma levels of NE and E from the control levels. Tre, Tsk, and Tb all showed greater declines with the addition of ketamine infusion to the cold exposure. Water exposure (28 degrees C) under ketamine anesthesia resulted in a drop in Tre to 33 degrees C within 1 h. Plasma levels of NE and E were unchanged from control values at Tre of 35 and 33 degrees C. The data suggest that the administration of ketamine abolished both the thermoregulatory response and the catecholamine response to acute cold exposure. PMID:6853296

  16. Neurovirulence of yellow fever 17DD vaccine virus to rhesus monkeys

    International Nuclear Information System (INIS)

    The yellow fever 17D virus is attenuated and used for human vaccination. Two of its substrains, 17D-204 and 17DD, are used for vaccine production. One of the remarkable properties of this vaccine is limited viral replication in the host but with significant dissemination of the viral mass, yielding a robust and long-lived neutralizing antibody response. The vaccine has excellent records of efficacy and safety and is cheap, used as a single dose, and there are well-established production methodology and quality control procedures which include the monkey neurovirulence test (MNTV). The present study aims at a better understanding of YF 17DD virus attenuation and immunogenicity in the MNVT with special emphasis on viremia, seroconversion, clinical and histological lesions scores, and their intrinsic variability across the tests. Several MNVTs were performed using the secondary seed lot virus 17DD 102/84 totaling 49 rhesus monkeys. Viremia was never higher than the accepted limits established in international requirements, and high levels of neutralizing antibodies were observed in all animals. None of the animals showed visceral lesions. We found that the clinical scores for the same virus varied widely across the tests. There was a direct correlation between the clinical scores in animals with clinical signs of encephalitis and a higher degree of central nervous system (CNS) histological lesions, with an increase of lesions in areas of the CNS such as the substantia nigra, nucleus caudatus, intumescentia cervicalis, and intumescentia ventralis. The histological scores were shown to be less prone to individual variations and had a more homogeneous value distribution among the tests. Since 17DD 102/84 seed virus has been used for human vaccine production and immunization for 16 years with the vaccine being safe and efficacious, it demonstrates that the observed variations across the MNVTs do not influence its effect on humans

  17. Kinetics of 11C-labeled opiates in the brain of rhesus monkeys

    International Nuclear Information System (INIS)

    The regional uptake in the brain of Rhesus monkeys of i.v. administered 11C-labeled morphine, codeine, heroin and pethidine was studied by means of positron emission tomography. The technique measures the sum of parent drug and radiolabeled metabolites. (For the sake of simplicity the drug derived radioactivity is denoted by the drug name.) Morphine had a limited uptake to discrete areas of the brain. The maximum normalized uptake, with respect to dose per kilogram body weight, was about 0.2, i.e., 20% of the calculated activity if the drug had been evenly distributed throughout the body of the monkey. Maximum radioactivity appeared 30 to 45 min after injection. Morphine left the brain slowly with an estimated half-life of more than 2 hr. An area with a normalized uptake of about 1.0 was detected centrally in the lowest horizontal transsection of the skull. The origin of this area was identified as the pituitary. Codeine, heroin and pethidine were taken up to the brain to a larger extent than morphine, with maximum normalized uptakes of 2.6, 4.6 and 6.3, respectively. Maximum radioactivities of these drugs were achieved earlier and the elimination rates were faster than for morphine. Differences in the uptake of these drugs to the brain, as well as differences in time to maximal normalized uptake and rate of disappearance are considered to reflect differences in the lipophilic character between the drugs. Pethidine had the most rapid and extensive uptake followed by heroin, codeine and morphine in order of decreasing lipophilicity

  18. Kinetics of 11C-labeled opiates in the brain of rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Hartvig, P.; Bergstroem, K.; Lindberg, B.; Lundberg, P.O.; Lundqvist, H.; Langstroem, B.; Svaerd, H.; Rane, A.

    1984-07-01

    The regional uptake in the brain of Rhesus monkeys of i.v. administered 11C-labeled morphine, codeine, heroin and pethidine was studied by means of positron emission tomography. The technique measures the sum of parent drug and radiolabeled metabolites. (For the sake of simplicity the drug derived radioactivity is denoted by the drug name.) Morphine had a limited uptake to discrete areas of the brain. The maximum normalized uptake, with respect to dose per kilogram body weight, was about 0.2, i.e., 20% of the calculated activity if the drug had been evenly distributed throughout the body of the monkey. Maximum radioactivity appeared 30 to 45 min after injection. Morphine left the brain slowly with an estimated half-life of more than 2 hr. An area with a normalized uptake of about 1.0 was detected centrally in the lowest horizontal transsection of the skull. The origin of this area was identified as the pituitary. Codeine, heroin and pethidine were taken up to the brain to a larger extent than morphine, with maximum normalized uptakes of 2.6, 4.6 and 6.3, respectively. Maximum radioactivities of these drugs were achieved earlier and the elimination rates were faster than for morphine. Differences in the uptake of these drugs to the brain, as well as differences in time to maximal normalized uptake and rate of disappearance are considered to reflect differences in the lipophilic character between the drugs. Pethidine had the most rapid and extensive uptake followed by heroin, codeine and morphine in order of decreasing lipophilicity.

  19. Imaging of aromatase distribution in rat and rhesus monkey brains with [{sup 11}C]vorozole

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Kayo [Division of Pharmacology, Department of Neuroscience, Uppsala University, Uppsala SE-75124 (Sweden); Uppsala Imanet, Uppsala SE-75109 (Sweden)]. E-mail: kayo.takahashi@uppsala.imanet.se; Bergstroem, Mats [Uppsala Imanet, Uppsala SE-75109 (Sweden); Department of Pharmaceutical Biosciences, Uppsala University, Uppsala SE-75124 (Sweden); Fraendberg, Pernilla [Uppsala Imanet, Uppsala SE-75109 (Sweden); Vesstroem, Eva-Lotta [Uppsala Imanet, Uppsala SE-75109 (Sweden); Watanabe, Yasuyoshi [Department of Physiology, Osaka City University Graduate School of Medicine, Osaka 545-8585 (Japan); Langstroem, Bengt [Uppsala Imanet, Uppsala SE-75109 (Sweden)

    2006-07-15

    Aromatase is an enzyme that converts androgens to estrogens and may play a role in mood and mental status. The aim of this study was to demonstrate that brain aromatase distribution could be evaluated with a novel positron emission tomography (PET) tracer [{sup 11}C]vorozole. Vorozole is a nonsteroidal aromatase inhibitor that reversibly binds to the heme domain of aromatase. In vitro experiments in rat brain, using frozen section autoradiography, illustrated specific binding in the medial amygdala (MA), the bed nucleus of stria terminalis (BST) and the preoptic area (POA) of male rat brain. Specific binding in female rat brain was found in the MA and the BST; however, the signals were lower than those of males. The K {sub d} of [{sup 11}C]vorozole binding to aromatase in MA was determined to be 0.60{+-}0.06 nM by Scatchard plot analysis using homogenates. An in vivo PET study in female rhesus monkey brain demonstrated the uptake of [{sup 11}C]vorozole in the amygdala, where the uptake was blocked by the presence of excess amounts of unlabeled vorozole. Thus, this tracer has a high affinity for brain aromatase and could have a potential for in vivo aromatase imaging. This technique might enable the investigation of human brain aromatase in healthy and diseased persons.

  20. Rhesus monkeys correctly read the goal-relevant gestures of a human agent.

    Science.gov (United States)

    Hauser, Marc D; Glynn, David; Wood, Justin

    2007-08-01

    When humans point, they reveal to others their underlying intent to communicate about some distant goal. A controversy has recently emerged based on a broad set of comparative and phylogenetically relevant data. In particular, whereas chimpanzees (Pan troglodytes) have difficulty in using human-generated communicative gestures and actions such as pointing and placing symbolic markers to find hidden rewards, domesticated dogs (Canis familiaris) and silver foxes (Urocyon cinereoargenteus) readily use such gestures and markers. These comparative data have led to the hypothesis that the capacity to infer communicative intent in dogs and foxes has evolved as a result of human domestication. Though this hypothesis has met with challenges, due in part to studies of non-domesticated, non-primate animals, there remains the fundamental question of why our closest living relatives, the chimpanzees, together with other non-human primates, generally fail to make inferences about a target goal of an agent's communicative intent. Here, we add an important wrinkle to this phylogenetic pattern by showing that free-ranging rhesus monkeys (Macaca mulatta) draw correct inferences about the goals of a human agent, using a suite of communicative gestures to locate previously concealed food. Though domestication and human enculturation may play a significant role in tuning up the capacity to infer intentions from communicative gestures, these factors are not necessary. PMID:17540661

  1. Effect of ionizing radiation on prostaglandins and gastric secretion in rhesus monkeys

    International Nuclear Information System (INIS)

    Early radiation toxicity is characterized by nausea and vomiting. We have previously shown that gastric emptying, gastric motility, and gastric secretion were suppressed after total body exposure to irradiation. In the present studies, we evaluated the relation between vomiting and gastric function in nine rhesus monkeys and explored the possible role of prostaglandins (PG) in these phenomena. The concentration of PG in plasma and gastric juice was determined using a standard radioimmunoassay and gastric acid output was measured concurrently using a marker dilution technique. The animals were studied in the basal state and after total body exposure to 800 cGy 60Co delivered at a rate of 500 cGy/min. Acid output was abolished from 40 min to 2 h after irradiation but had returned to preirradiation levels 2 days later. Plasma PGE2 and PGI2 (as measured by 6-keto-PGF1 alpha determination) were not significantly modified by irradiation. In contrast, irradiation produced an immediate significant increase (P less than 0.05) in gastric juice concentration of PGE2 (318 +/- 80 to 523 +/- 94 pg/ml; mean +/- SE) and PGI2 (230 +/- 36 to 346 +/- 57 pg/ml); both had returned to basal levels 2 days later. Thus, an increase in gastric juice concentration of both PGE2 and PGI2 is associated with the radiation induced suppression of acid output

  2. New noninvasive imaging technique for cataract evaluation in the rhesus monkey

    Science.gov (United States)

    DiCarlo, Cheryl D.; Boppart, Stephen A.; Gagliano, Donald A.; Amnotte, Rodney E.; Smith, Audrey B.; Hammer, Daniel X.; Cox, Ann B.; Hee, Michael R.; Fujimoto, James G.; Swanson, Eric A.; Roach, William P.

    1995-05-01

    We present the first in vivo study using Optical Coherence Tomography (OCT) as the imaging device for lenticular cataracts in the geriatric rhesus monkey. OCT is a non-invasive imaging technique that produces a 2D cross sectional image of intraocular tissue similar to ultrasound B scan. In OCT the images are formed by measuring optical reflections from the tissue. Eighteen geriatric subjects with documented lenticular opacities and one control subject were imaged. The OCT images produced are compared to current and previous clinical cataract grading exams and slit-lamp photography. Histopathology was collected on one subject and is compared to the OCT image. OCT provides information on nuclear, cortical and subcapsular opacities. The image formation is presented based on a color coded computer generated log reflective scale. The log reflective scale is converted to a qualitative grading system. Although movement and shadow artifact can occur, these are readily identifiable and can be differentiated from underlying lenticular abnormalities. OCT has great potential to assist in further characterization of cataracts.

  3. Cholinergic neuronal differentiation of bone marrow mesenchymal stem cells in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The purpose of the present study was to determine the best cholinergic neuronal differentiation method of rhesus monkey bone marrow mesenchymal stem cells(BMSCs).Four methods were used to induce differentiation,and the groups were assigned accordingly:basal inducing group(culture media,bFGF,and forskolin);SHH inducing group(SHH,inducing group);RA inducing group(RA,basal inducing group);and SHH+RA inducing group(SHH,RA,and basal inducing group).All groups displayed neuronal morphology and increased expression of nestin and neuron-specific enolase.The basal inducing group did not express synapsin,and cells from the SHH inducing group did not exhibit neuronal resting membrane potential.In contrast,results demonstrated that BMSCs from the RA and SHH+RA inducing groups exhibited neuronal resting membrane potential,and cells from the SHH+RA inducing group expressed higher levels of synapsin and acetylcholine.In conclusion,the induction of cholinergic differentiation through SHH+RA was determined to be superior to the other methods.

  4. Contractile properties of rat, rhesus monkey, and human type I muscle fibers

    Science.gov (United States)

    Widrick, J. J.; Romatowski, J. G.; Karhanek, M.; Fitts, R. H.

    1997-01-01

    It is well known that skeletal muscle intrinsic maximal shortening velocity is inversely related to species body mass. However, there is uncertainty regarding the relationship between the contractile properties of muscle fibers obtained from commonly studied laboratory animals and those obtained from humans. In this study we determined the contractile properties of single chemically skinned fibers prepared from rat, rhesus monkey, and human soleus and gastrocnemius muscle samples under identical experimental conditions. All fibers used for analysis expressed type I myosin heavy chain as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Allometric coefficients for type I fibers from each muscle indicated that there was little change in peak tension (force/fiber cross-sectional area) across species. In contrast, both soleus and gastrocnemius type I fiber maximal unloaded shortening velocity (Vo), the y-intercept of the force-velocity relationship (Vmax), peak power per unit fiber length, and peak power normalized for fiber length and cross-sectional area were all inversely related to species body mass. The present allometric coefficients for soleus fiber Vo (-0.18) and Vmax (-0.11) are in good agreement with published values for soleus fibers obtained from common laboratory and domesticated mammals. Taken together, these observations suggest that the Vo of slow fibers from quadrupeds and humans scale similarly and can be described by the same quantitative relationships. These findings have implications in the design and interpretation of experiments, especially those that use small laboratory mammals as a model of human muscle function.

  5. Imaging of aromatase distribution in rat and rhesus monkey brains with [11C]vorozole

    International Nuclear Information System (INIS)

    Aromatase is an enzyme that converts androgens to estrogens and may play a role in mood and mental status. The aim of this study was to demonstrate that brain aromatase distribution could be evaluated with a novel positron emission tomography (PET) tracer [11C]vorozole. Vorozole is a nonsteroidal aromatase inhibitor that reversibly binds to the heme domain of aromatase. In vitro experiments in rat brain, using frozen section autoradiography, illustrated specific binding in the medial amygdala (MA), the bed nucleus of stria terminalis (BST) and the preoptic area (POA) of male rat brain. Specific binding in female rat brain was found in the MA and the BST; however, the signals were lower than those of males. The K d of [11C]vorozole binding to aromatase in MA was determined to be 0.60±0.06 nM by Scatchard plot analysis using homogenates. An in vivo PET study in female rhesus monkey brain demonstrated the uptake of [11C]vorozole in the amygdala, where the uptake was blocked by the presence of excess amounts of unlabeled vorozole. Thus, this tracer has a high affinity for brain aromatase and could have a potential for in vivo aromatase imaging. This technique might enable the investigation of human brain aromatase in healthy and diseased persons

  6. Stereoselectivity in the disposition and metabolism of the uricosuric-diuretic agent, indacrinone, in Rhesus monkeys

    International Nuclear Information System (INIS)

    The physiological disposition following intravenous dosing of the separate enantiomers of indacrinone-14C (I), and of their major metabolite, 4'-hydroxyindacrinone-14C (M), was studied in the rhesus monkey. Pharmacokinetic analysis indicated that the disposition of I and M was stereoselective. In the case of the enantiomers of I, the areas under the curves of plasma concentration vs. time were about sevenfold greater for the (S)(+)- as compared to the (R)(-)-enantiomer. Renal and plasma clearances of (R)(-)-I were five to seven times greater than those of (S)(+)-I. Total urinary recovery of unchanged drug and metabolite accounted for 70% of the administered dose of either enantiomer. The systemic availability of (R)(-)-M from (R)(-)-I was approximately 21% of the dose, whereas that of (S)(+)-M from (S)(+)-I was only 4%. More pronounced differences were noted in the kinetics of metabolite disposition. The AUC values were about 27 times greater for (S)(+)-M than (R)(-)-M, and the renal and plasma clearances were approximately 25-fold higher for (R)(-)-M as compared to (S)(+)-M. The volume of distribution of (S)(+)-M was only 12% of that observed with (R)(+)-M. There was no evidence of glucuronide or sulfate conjugates of any of the enantiomers. These findings are consistent with the pharmacological activity attributed to the different enantiomers

  7. Biobehavioral consequences of prenatal exposure to a matrilineal overthrow and relocation in captive infant rhesus (Macaca mulatta) monkeys.

    Science.gov (United States)

    Herrington, Joshua A; Del Rosso, Laura A; Capitanio, John P

    2016-09-01

    There is a general consensus that perinatal experiences help to shape infant behavior; however, relatively little is known about the effects of prenatal experience on postnatal phenotype in non-human primates. The current study sought to take advantage of a naturally occurring incident in a captive population of rhesus monkeys. Following a matrilineal overthrow in an outdoor field cage, pregnant female rhesus macaques were relocated from outdoor to indoor housing. Using data collected from the California National Primate Research Center's Biobehavioral Assessment Program, we assessed infants born to mothers that were in their first or second trimester of pregnancy during the overthrow and relocation, and compared their data with that of animals from two control groups born in the same year: indoor mother raised infants and field cage reared infants. Our results suggest that the experience of an overthrow and relocation during the first trimester elevated postnatal emotional responsiveness, while the same experience in the second trimester resulted in modified HPA axis regulation, elevated glucocorticoid output following maternal separation, and lower hematocrit levels compared to control groups. These data add to a growing body of literature that prenatal experiences represent a significant contribution to postnatal phenotypic variability. Findings such as ours have implications for studies in captive management and the management of captive rhesus monkey populations. Am. J. Primatol. 78:895-903, 2016. © 2016 Wiley Periodicals, Inc. PMID:27150125

  8. Protection of rhesus monkeys from fatal Lassa fever by vaccination with a recombinant vaccinia virus containing the Lassa virus glycoprotein gene.

    OpenAIRE

    Fisher-Hoch, S P; McCormick, J. B.; Auperin, D; Brown, B G; Castor, M; Perez, G; Ruo, S; Conaty, A; Brammer, L.; S. Bauer

    1989-01-01

    Lassa fever is an acute febrile disease of West Africa, where there are as many as 300,000 infections a year and an estimated 3000 deaths. As control of the rodent host is impracticable at present, the best immediate prospect is vaccination. We tested as potential vaccines in rhesus monkeys a closely related virus, Mopeia virus (two monkeys), and a recombinant vaccinia virus containing the Lassa virus glycoprotein gene, V-LSGPC (four monkeys). Two monkeys vaccinated with the New York Board of...

  9. The migration of 111Indium-labelled polymorphonuclear leucocytes into the oral cavity in the rhesus monkey

    International Nuclear Information System (INIS)

    The route of migration of polymorphonuclear leucocytes (PMNL) from blood to the oral cavity was examined in rhesus monkeys. PMNL were isolated from the peripheral blood of eleven rhesus monkeys by dextran sedimentation, radiolabelled with 111Indium and administered intravenously. Sequential samples of crevicular fluid washings (CFW), mixed and parotid saliva and mucosal washings were taken after injection of the labelled PMNL and harvested on glass fibre discs. Highest numbers of labelled PMNL were detected in CFW. CEll-associated radioactivity was detected in CFW within 20 min of injection of labelled PMNL and reached a maximal level 1 hour after injection. PMNL were found in CFW from monkeys with clinically normal gingiva but the number of labelled PMNL in CFW increased with increasing gingival index. Significant number of PMNL migrated into mixed saliva within 30 min, and low numbers of PMNL were detected in mucosal washings and in parotid saliva after 30 min. The results indicate that the migration time of the PMNL from blood to the oral cavity is less than 30 min, irrespective of the gingival index, that the gingival crevice is the main route of entry of PMNL to the oral cavity and that the numbers of PMNL migrating to the crevice increase as the gingival index rises. (author)

  10. Short-term testosterone manipulations do not affect cognition or motor function but differentially modulate emotions in young and older male rhesus monkeys.

    Science.gov (United States)

    Kelly, Brian; Maguire-Herring, Vanessa; Rose, Christian M; Gore, Heather E; Ferrigno, Stephen; Novak, Melinda A; Lacreuse, Agnès

    2014-11-01

    Human aging is characterized by declines in cognition and fine motor function as well as improved emotional regulation. In men, declining levels of testosterone (T) with age have been implicated in the development of these age-related changes. However, studies examining the effects of T replacement on cognition, emotion and fine motor function in older men have not provided consistent results. Rhesus monkeys (Macaca mulatta) are excellent models for human cognitive aging and may provide novel insights on this issue. We tested 10 aged intact male rhesus monkeys (mean age=19, range 15-25) on a battery of cognitive, motor and emotional tasks at baseline and under low or high T experimental conditions. Their performance was compared to that of 6 young males previously tested in the same paradigm (Lacreuse et al., 2009; Lacreuse et al., 2010). Following a 4-week baseline testing period, monkeys were treated with a gonadotropin releasing hormone agonist (Depot Lupron, 200 μg/kg) to suppress endogenous T and were tested on the task battery under a 4-week high T condition (injection of Lupron+T enanthate, 20 mg/kg, n=8) or 4-week low T condition (injection of Lupron+oil vehicle, n=8) before crossing over to the opposite treatment. The cognitive tasks consisted of the Delayed Non-Matching-to-Sample (DNMS), the Delayed Response (DR), and the Delayed Recognition Span Test (spatial-DRST). The emotional tasks included an object Approach-Avoidance task and a task in which monkeys were played videos of unfamiliar conspecifics in different emotional context (Social Playbacks). The fine motor task was the Lifesaver task that required monkeys to remove a Lifesaver candy from rods of different complexity. T manipulations did not significantly affect visual recognition memory, working memory, reference memory or fine motor function at any age. In the Approach-Avoidance task, older monkeys, but not younger monkeys, spent more time in proximity of novel objects in the high T condition

  11. Sleeve bridging of the rhesus monkey ulnar nerve with muscular branches of the pronator teres: multiple amplification of axonal regeneration

    Directory of Open Access Journals (Sweden)

    Yu-hui Kou

    2015-01-01

    Full Text Available Multiple-bud regeneration, i.e., multiple amplification, has been shown to exist in peripheral nerve regeneration. Multiple buds grow towards the distal nerve stump during proximal nerve fiber regeneration. Our previous studies have verified the limit and validity of multiple amplification of peripheral nerve regeneration using small gap sleeve bridging of small donor nerves to repair large receptor nerves in rodents. The present study sought to observe multiple amplification of myelinated nerve fiber regeneration in the primate peripheral nerve. Rhesus monkey models of distal ulnar nerve defects were established and repaired using muscular branches of the right forearm pronator teres. Proximal muscular branches of the pronator teres were sutured into the distal ulnar nerve using the small gap sleeve bridging method. At 6 months after suture, two-finger flexion and mild wrist flexion were restored in the ulnar-sided injured limbs of rhesus monkey. Neurophysiological examination showed that motor nerve conduction velocity reached 22.63 ± 6.34 m/s on the affected side of rhesus monkey. Osmium tetroxide staining demonstrated that the number of myelinated nerve fibers was 1,657 ± 652 in the branches of pronator teres of donor, and 2,661 ± 843 in the repaired ulnar nerve. The rate of multiple amplification of regenerating myelinated nerve fibers was 1.61. These data showed that when muscular branches of the pronator teres were used to repair ulnar nerve in primates, effective regeneration was observed in regenerating nerve fibers, and functions of the injured ulnar nerve were restored to a certain extent. Moreover, multiple amplification was subsequently detected in ulnar nerve axons.

  12. Cloning and Analysis of microRNAs Encoded by the Primate γ-Herpesvirus Rhesus Monkey Rhadinovirus

    OpenAIRE

    Schäfer, Alexandra; Cai, Xuezhong; Bilello, John P.; Desrosiers, Ronald C.; Cullen, Bryan R.

    2007-01-01

    Several pathogenic human herpesviruses have recently been shown to express virally encoded microRNAs in infected cells. Although the function of these microRNAs is largely unknown, they are hypothesized to play a role in mediating viral replication by down-regulating cellular mRNAs encoding antiviral factors. Here, we report the cloning and analysis of microRNAs encoded by Rhesus Monkey Rhadinovirus (RRV), an animal virus model for the pathogenic human γ-herpesvirus Kaposi’s Sarcoma-Associate...

  13. Differential Antagonism of Cocaine Self-Administration and Cocaine-Induced Disruptions of Learning by Haloperidol in Rhesus Monkeys

    OpenAIRE

    Winsauer, Peter J.; Moerschbaecher, Joseph M.; Roussell, Alison M

    2008-01-01

    Six rhesus monkeys responding under a three-component multiple schedule were administered haloperidol to determine its effects on cocaine self-administration and on cocaine's disruptive effects on the repeated acquisition and performance of response chains. In the absence of haloperidol, 0.0032–0.032 mg/kg/infusion of cocaine increased response rate and the number of infusions in the self-administration component when compared to saline administration, whereas 0.1–0.32 mg/kg/infusion decrease...

  14. Patterns of transfer of tritiated progesterone into blood and cerebrospinal fluid of rhesus monkeys following diverse methods of administration

    International Nuclear Information System (INIS)

    Tritiated progesterone (3H-P) was administered to adult ovariectomized rhesus monkeys by different routes and methods. About 200 Ci of 3H-P was administered to each monkey by intravenous injection, as eye drops, intranasal spray of a solution containing 3H-P or intranasal spray of powdered dextrose containing adsorbed 3H-P. Radioactivity was estimated in cerebrospinal fluid (csf) and serum at 5, 10, 15, 30, 60 and 120 min after administering the steroid, and the data expressed as ratios radioactivity (dpm/ml) in csf and serum. There was no difference in csf: serum ratios following intravenous or ocular routes of administration. The intransal routes of administration differed from the intravenous and the ocular routes in that the ratios showed a slow but gradual increase and also higher values. (author)

  15. Reproductive dysfunction in rhesus monkeys exposed to low levels of polychlorinated biphenyls (Aroclor 1248)

    Energy Technology Data Exchange (ETDEWEB)

    Barsotti, D.A.; Marlar, R.J.; Allen, J.R.

    1976-01-01

    Eighteen female and four male adult Rhesus monkeys were fed the polychlorinated biphenyl (PCB) Aroclor 1248 at levels of either 2.5 or 5.0 ppM in the diet. These levels are equal to, and 50% of, the concentration allowed in certain foods destined for human consumption. After consuming these diets for 2 months, some of the females developed acne, alopecia, erythema and swelling of the eyelids, and by 6 months all females exhibited these changes to some degree. Modifications in serum lipids developed gradually, with a trend towards hypocholesterolaemia, hypolipidaemia and decreased serum triglycerides. In addition there was a shift in the plasma albumin/globulin ratio and an increase in serum glutamic-pyruvic transaminase activity. Analysis of subcutaneous fat showed an accumulation of the PCB isomers in the adipose tissue. The concentrations in this tissue reached a plateau, after which only slight variations were observed. Within 4 months, menstrual cycles were altered: menostaxis and menorrhagia occurred frequently and at times amenorrhoea was apparent. The ability of the animals to maintain pregnancy was impaired, as indicated by frequent resorptions and abortions. When infants were born they were small, and the transplacental movement of PCBs was evident from analyses of skin biopsies of neonates and of autopsy tissue from one stillborn. Moreover, additional accumulation of PCBs occurred in infants during breast feeding. All males fed 5.0 ppM PCB exhibited only slight periorbital oedema and erythema after 14 months on the diet and showed no alterations in their breeding capacities. The data presented indicate that long-term, low-level exposure of female non-human primates to PCBs can affect many important biological parameters.

  16. Dopaminergic dysregulation in prefrontal cortex of rhesus monkeys following cocaine self-administration

    Directory of Open Access Journals (Sweden)

    Scot eMcIntosh

    2013-08-01

    Full Text Available Chronic cocaine administration regulates the expression of several proteins related to dopaminergic signaling and synaptic function in the mesocorticolimbic pathway, including the prefrontal cortex. Functional abnormalities in the prefrontal cortex are hypothesized to be due in part to the expression of proteins involved in dopamine signaling and plasticity. Adult male rhesus monkeys self-administered cocaine (i.v. under limited (n=4 and extended access conditions (n=6. The abundance of surrogate markers of dopamine signaling and plasticity in the dorsolateral prefrontal cortex (DLPFC, orbitofrontal cortex (OFC and anterior cingulate cortex (ACC were examined: glycosylated and non-glycosylated forms of the dopamine transporter (efficiency of dopamine transport, tyrosine hydroxylase (TH; marker of dopamine synthesis and phosphorylated TH at Serine 30 and 40 (markers of enzyme activity, extracellular signal-regulated kinase 1 and 2 (ERK1 and ERK 2 and phosphorylated ERK1 and ERK2 (phosphorylates TH Serine 31; markers of synaptic plasticity, and markers of synaptic integrity, spinophilin and post-synaptic density protein 95 (roles in dopamine signaling and response to cocaine. Extended cocaine access increased non-glycosylated and glycosylated DAT in DLPFC and OFC. While no differences in TH expression were observed between groups for any of the regions, extended access induced significant elevations in pTHSer31 in all regions. In addition, a slight but significant reduction in phosphorylated pTHSer40 was found in the DLPFC. Phosphorylated ERK2 was increased in all regions; however, pERK1 was decreased in ACC and OFC but increased in DLPFC. PSD-95 was increased in the OFC but not in DLPFC or ACC. Furthermore, extended cocaine self-administration elicited significant increases in spinophilin protein expression in all regions. Results from the study provide insight into the biochemical alterations occurring in primate prefrontal cortex.

  17. Multilineage differentiation of rhesus monkey embryonic stem cells in three-dimensional culture systems

    Science.gov (United States)

    Chen, Silvia S.; Revoltella, Roberto P.; Papini, Sandra; Michelini, Monica; Fitzgerald, Wendy; Zimmerberg, Joshua; Margolis, Leonid

    2003-01-01

    In the course of normal embryogenesis, embryonic stem (ES) cells differentiate along different lineages in the context of complex three-dimensional (3D) tissue structures. In order to study this phenomenon in vitro under controlled conditions, 3D culture systems are necessary. Here, we studied in vitro differentiation of rhesus monkey ES cells in 3D collagen matrixes (collagen gels and porous collagen sponges). Differentiation of ES cells in these 3D systems was different from that in monolayers. ES cells differentiated in collagen matrixes into neural, epithelial, and endothelial lineages. The abilities of ES cells to form various structures in two chemically similar but topologically different matrixes were different. In particular, in collagen gels ES cells formed gland-like circular structures, whereas in collagen sponges ES cells were scattered through the matrix or formed aggregates. Soluble factors produced by feeder cells or added to the culture medium facilitated ES cell differentiation into particular lineages. Coculture with fibroblasts in collagen gel facilitated ES cell differentiation into cells of a neural lineage expressing nestin, neural cell adhesion molecule, and class III beta-tubulin. In collagen sponges, keratinocytes facilitated ES cell differentiation into cells of an endothelial lineage expressing factor VIII. Exogenous granulocyte-macrophage colony-stimulating factor further enhanced endothelial differentiation. Thus, both soluble factors and the type of extracellular matrix seem to be critical in directing differentiation of ES cells and the formation of tissue-like structures. Three-dimensional culture systems are a valuable tool for studying the mechanisms of these phenomena.

  18. Spaceflight effects on single skeletal muscle fiber function in the rhesus monkey

    Science.gov (United States)

    Fitts, R. H.; Desplanches, D.; Romatowski, J. G.; Widrick, J. J.

    2000-01-01

    The purpose of this investigation was to understand how 14 days of weightlessness alters the cellular properties of individual slow- and fast-twitch muscle fibers in the rhesus monkey. The diameter of the soleus (Sol) type I, medial gastrocnemius (MG) type I, and MG type II fibers from the vivarium controls averaged 60 +/- 1, 46 +/- 2, and 59 +/- 2 microm, respectively. Both a control 1-G capsule sit (CS) and spaceflight (SF) significantly reduced the Sol type I fiber diameter (20 and 13%, respectively) and peak force, with the latter declining from 0.48 +/- 0.01 to 0.31 +/- 0.02 (CS group) and 0.32 +/- 0.01 mN (SF group). When the peak force was expressed as kiloNewtons per square meter (kN/m(2)), only the SF group showed a significant decline. This group also showed a significant 15% drop in peak fiber stiffness that suggests that fewer cross bridges were contracting in parallel. In the MG, SF but not CS depressed the type I fiber diameter and force. Additionally, SF significantly depressed absolute (mN) and relative (kN/m(2)) force in the fast-twitch MG fibers by 30% and 28%, respectively. The Ca(2+) sensitivity of the type I fiber (Sol and MG) was significantly reduced by growth but unaltered by SF. Flight had no significant effect on the mean maximal fiber shortening velocity in any fiber type or muscle. The post-SF Sol type I fibers showed a reduced peak power and, at peak power, an elevated velocity and decreased force. In conclusion, CS and SF caused atrophy and a reduced force and power in the Sol type I fiber. However, only SF elicited atrophy and reduced force (mN) in the MG type I fiber and a decline in relative force (kN/m(2)) in the Sol type I and MG type II fibers.

  19. EVALUATION OF IMMUNOTOXICITY OF THE THERAPEUTIC DRUG PROLONGED ACTION FOR MULTIPLE SCLEROSIS ON RHESUS MONKEYS

    Directory of Open Access Journals (Sweden)

    A. B. Dzheliya

    2015-10-01

    Full Text Available This article presents the results of immunotoxicity study of a novel slow-release drug for multiple sclerosis treatment based on recombinant human interferon beta-1а. The test article is polyethylene glycol (PEG-conjugated interferon beta-1a. Performed modification allows to improve pharmacokinetic parameters, decrease immunogenicity and elevate tolerance that significantly increases safety of the test article. The study is performed in nonhuman primates – rhesus monkeys (Macaca mulatta. The species, used in this study, is susceptible to human interferon beta-1a that has previously been shown in specific activity studies. Dynamics of peripheral blood lymphocyte subsets composition, activated lymphocyte count (based on the presence of early activation marker, serum antibodies (IgM, IgG, IgA and IgE level and ratio were assessed within in vivo experiments. The effect of interferon beta-1a on CD69 expression was examined in mononuclear cells culture. It was shown that the test article causes changes in lymphocyte subsets ratio (decrease of NK-cells relative count with T-lymphocytes relative count elevation in primates’ peripheral blood. Revealed changes were reversible and dose-independent. It was not shown that the test article have reliable effect on CD69 expression rate. There was no evidence of test article effect on level and ratio of serum antibodies and polymorphonucleocytes phagocytic rate in the absence of additional antigenic exposure. The results obtained during the experiment indicate the absence of pathological effect of the test article on the nonhuman primates’ immune system.

  20. Association fiber pathways to the frontal cortex from the superior temporal region in the rhesus monkey

    International Nuclear Information System (INIS)

    The projections to the frontal cortex that originate from the various areas of the superior temporal region of the rhesus monkey were investigated with the autoradiographic technique. The results demonstrated that the rostral part of the superior temporal gyrus (areas Pro, Ts1, and Ts2) projects to the proisocortical areas of the orbital and medial frontal cortex, as well as to the nearby orbital areas 13, 12, and 11, and to medial areas 9, 10, and 14. These fibers travel to the frontal lobe as part of the uncinate fascicle. The middle part of the superior temporal gyrus (areas Ts3 and paAlt) projects predominantly to the lateral frontal cortex (areas 12, upper 46, and 9) and to the dorsal aspect of the medial frontal lobe (areas 9 and 10). Only a small number of these fibers terminated within the orbitofrontal cortex. The temporofrontal fibers originating from the middle part of the superior temporal gyrus occupy the lower portion of the extreme capsule and lie just dorsal to the fibers of the uncinate fascicle. The posterior part of the superior temporal gyrus projects to the lateral frontal cortex (area 46, dorsal area 8, and the rostralmost part of dorsal area 6). Some of the fibers from the posterior superior temporal gyrus run initially through the extreme capsule and then cross the claustrum as they ascend to enter the external capsule before continuing their course to the frontal lobe. A larger group of fibers curves round the caudalmost Sylvian fissure and travels to the frontal cortex occupying a position just above and medial to the upper branch of the circular sulcus. This latter pathway constitutes a part of the classically described arcuate fasciculus

  1. Intrinsic connections and architectonics of posterior parietal cortex in the rhesus monkey

    International Nuclear Information System (INIS)

    By means of autoradiographic and ablation-degeneration techniques, the intrinsic cortical connections of the posterior parietal cortex in the rhesus monkey were traced and correlated with a reappraisal of cerebral architectonics. Two major rostral-to-caudal connectional sequences exist. One begins in the dorsal postcentral gyrus (area 2) and proceeds, through architectonic divisions of the superior parietal lobule (areas PE and PEc), to a cortical region on the medial surface of the parietal lobe (area PGm). This area has architectonic features similar to those of the caudal inferior parietal lobule (area PG). The second sequence begins in the ventral post/central gyrus (area 2) and passes through the rostral inferior parietal lobule (areas PG and PFG) to reach the caudal inferior parietal lobule (area PG). Both the superior parietal lobule and the rostral inferior parietal lobule also send projections to various other zones located in the parietal opercular region, the intraparietal sulcus, and the caudalmost portion of the cingulate sulcus. Areas PGm and PG, on the other hand, project to each other, to the cingulate region, to the caudalmost portion of the superior temporal gyrus, and to the upper bank of the superior temporal sulcus. Finally, a reciprocal sequence of connections, directed from caudal to rostral, links together many of the above-mentioned parietal zones. With regard to the laminar pattern of termination, the rostral-to-caudal connections are primarily distributed in the form of cortical ''columns'' while the caudal-to-rostral connections are found mainly over the first cortical cell layer

  2. Depressive-Like Behavioral Response of Adult Male Rhesus Monkeys during Routine Animal Husbandry Procedure

    Directory of Open Access Journals (Sweden)

    Michael B Hennessy

    2014-09-01

    Full Text Available Social isolation is a major risk factor for the development of depressive illness; yet, no practical nonhuman primate model is available for studying processes involved in this effect. In a first study, we noted that adult male rhesus monkeys housed individually indoors occasionally exhibited a hunched, depressive-like posture. Therefore, Study 2 investigated the occurrence of a hunched posture by adult males brought from outdoor social groups to indoor individual housing. We also scored two other behaviors—lying on the substrate and day time sleeping—that convey an impression of depression. During the first week of observation following individual housing, 18 of 26 adult males exhibited the hunched posture and 21 of 26 displayed at least one depressive-like behavior. Over 2 weeks, 23 of 26 males showed depressive-like behavior during a total of only 20 min observation. Further, the behavior during the first week was positively related to the level of initial response to a maternal separation procedure experienced in infancy. In Study 3, more than half of 23 adult males of a new sample displayed depressive-like behavior during 10 min of observation each of Weeks 7 to 14 of individual housing. The surprisingly high frequency of depressive-like behavior in Studies 2 and 3 may have been due to recording behavior via camera with no human in the room to elicit competing responses. These results suggest that a common animal husbandry procedure might provide a practical means for examining effects of social isolation on depression-related endpoints in a nonhuman primate. The findings also suggest that trait-like differences in emotional responsiveness during separation in infancy may predict differences in responsiveness during social isolation in adulthood.

  3. Depressive-like behavioral response of adult male rhesus monkeys during routine animal husbandry procedure.

    Science.gov (United States)

    Hennessy, Michael B; McCowan, Brenda; Jiang, Jing; Capitanio, John P

    2014-01-01

    Social isolation is a major risk factor for the development of depressive illness; yet, no practical nonhuman primate model is available for studying processes involved in this effect. In a first study, we noted that adult male rhesus monkeys housed individually indoors occasionally exhibited a hunched, depressive-like posture. Therefore, Study 2 investigated the occurrence of a hunched posture by adult males brought from outdoor social groups to indoor individual housing. We also scored two other behaviors-lying on the substrate and day time sleeping-that convey an impression of depression. During the first week of observation following individual housing, 18 of 26 adult males exhibited the hunched posture and 21 of 26 displayed at least one depressive-like behavior. Over 2 weeks, 23 of 26 males showed depressive-like behavior during a total of only 20 min observation. Further, the behavior during the first week was positively related to the level of initial response to a maternal separation procedure experienced in infancy. In Study 3, more than half of 23 adult males of a new sample displayed depressive-like behavior during 10 min of observation each of Weeks 7-14 of individual housing. The surprisingly high frequency of depressive-like behavior in Studies 2 and 3 may have been due to recording behavior via camera with no human in the room to elicit competing responses. These results suggest that a common animal husbandry procedure might provide a practical means for examining effects of social isolation on depression-related endpoints in a nonhuman primate. The findings also suggest that trait-like differences in emotional responsiveness during separation in infancy may predict differences in responsiveness during social isolation in adulthood. PMID:25249954

  4. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys.

    Science.gov (United States)

    Warren, Travis K; Jordan, Robert; Lo, Michael K; Ray, Adrian S; Mackman, Richard L; Soloveva, Veronica; Siegel, Dustin; Perron, Michel; Bannister, Roy; Hui, Hon C; Larson, Nate; Strickley, Robert; Wells, Jay; Stuthman, Kelly S; Van Tongeren, Sean A; Garza, Nicole L; Donnelly, Ginger; Shurtleff, Amy C; Retterer, Cary J; Gharaibeh, Dima; Zamani, Rouzbeh; Kenny, Tara; Eaton, Brett P; Grimes, Elizabeth; Welch, Lisa S; Gomba, Laura; Wilhelmsen, Catherine L; Nichols, Donald K; Nuss, Jonathan E; Nagle, Elyse R; Kugelman, Jeffrey R; Palacios, Gustavo; Doerffler, Edward; Neville, Sean; Carra, Ernest; Clarke, Michael O; Zhang, Lijun; Lew, Willard; Ross, Bruce; Wang, Queenie; Chun, Kwon; Wolfe, Lydia; Babusis, Darius; Park, Yeojin; Stray, Kirsten M; Trancheva, Iva; Feng, Joy Y; Barauskas, Ona; Xu, Yili; Wong, Pamela; Braun, Molly R; Flint, Mike; McMullan, Laura K; Chen, Shan-Shan; Fearns, Rachel; Swaminathan, Swami; Mayers, Douglas L; Spiropoulou, Christina F; Lee, William A; Nichol, Stuart T; Cihlar, Tomas; Bavari, Sina

    2016-03-17

    The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg(-1) GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the

  5. Expression of insulin-like growth factor-1 mRNA and protein level of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    Huanmin Gao; Rui Zhang; Yunliang Guo

    2006-01-01

    BACKGROUND: Insulin-like growth factor-I(IGF-1), as one of the important members of growth factor family,participants in the regulation of many physiological functions and behaviors, having very strong neuroprotective effect. However, the expression of IGF-1 following cerebral ischemia/reperfusion is still disputed.OBJ ECTIVE: To observe the expression of IGF-1 and protein of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkey.DESIGN: A completely randomized grouping design, controlled animal experimentSETTING: Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University.MATERIALS: ① Totally 17 rhesus monkeys , of either gender, aged 4 to 5 years, were enrolled . Seven rhesus monkeys observed with gene chip were randomly divided into 2 groups: sham operation group (n=3)and ischemia/reperfusion group (n=4). Ten rhesus monkeys observed with in situ hybridization and immunohistochemistry method were randomly divided into 2 groups: sham operation group (n=3)and ischemia/reperfusion group (n=7). Rhesus monkeys observed under microscope were divided into 2 groups: sham operation group (n=6) and ischamia/reperfusion group (n=11). ② Materials used in the experiment: cresyl violet (Sigma Company, America); immunohistochemical reagent kit ( Huamei Bio-engineering Company); In situ hybridization reagent kit (Boshide Bio-engineering Co. Ltd, Wuhan); 12 800 dots chip (Boxing Company,Shanghai).METHODS: This experiment was carried out at the Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University from January 2001 to December 2003. ① The onset area of middle cerebral artery was blocked for 2 hours, middle cerebral artery ischemia/reperfusion models were created.② After ischemia/reperfusion for 24 hours, cerebral tissue sections of rhesus monkeys were prepared and stained with cresyl violet. Image analysis was performed with 500IW

  6. Mechanisms of Withdrawal-Associated Increases in Heroin Self-Administration: Pharmacologic Modulation of Heroin vs. Food Choice in Heroin-Dependent Rhesus Monkeys

    OpenAIRE

    Negus, S. Stevens; Rice, Kenner C.

    2008-01-01

    Opioid withdrawal can produce a constellation of physiological and behavioral signs, including an increase in opioid self-administration. Different mechanisms mediate different withdrawal signs, and the present study used pharmacologic tools to assess mechanisms underlying withdrawal-associated increases in opioid reinforcement. Five rhesus monkeys were rendered heroin dependent via daily 21-hr heroin self-administration sessions. One hr after each heroin self-administration session, monkeys ...

  7. Long-Term Exposure to Oral Methylphenidate or dl-Amphetamine Mixture in Peri-Adolescent Rhesus Monkeys: Effects on Physiology, Behavior, and Dopamine System Development

    OpenAIRE

    Soto, Paul L.; Wilcox, Kristin M.; Zhou, Yun; Ator, Nancy A.; Riddle, Mark A.; Wong, Dean F.; Weed, Michael R.

    2012-01-01

    The stimulants methylphenidate and amphetamine are used to treat children with attention deficit/hyperactivity disorder over important developmental periods, prompting concerns regarding possible long-term health impact. This study assessed the effects of such a regimen in male, peri-adolescent rhesus monkeys on a variety of cognitive/behavioral, physiological, and in vivo neurochemical imaging parameters. Twice daily (0900 and 1200 hours), for a total of 18 months, juvenile male monkeys (8 p...

  8. Optimal Iron Fortification of Maternal Diet during Pregnancy and Nursing For Investigating and Preventing Iron Deficiency in Young Rhesus Monkeys1

    OpenAIRE

    Coe, Christopher L.; Lubach, Gabriele R.; Busbridge, Mark; Chapman, Richard S.

    2013-01-01

    The realization that pregnant and infant monkeys were challenged by high nutritional needs for iron led vendors to markedly increase iron concentrations in commercial diets. Yet, no systematic research was conducted to investigate the consequences of this important dietary change. Hematology and iron panels were determined for 142 infant rhesus monkeys gestated and reared on 3 different diets varying in iron concentration (180, 225 or 380 mg Fe/kg). Anemia was significantly more prevalent in ...

  9. Quantitative histological studies on aging changes in cerebral cortex of rhesus monkey and albino rat with notes on effects of prolonged low-dose ionizing irradiation in the rat

    International Nuclear Information System (INIS)

    Brains of a series of eight young adult control (150 days) and eight middle-aged control (550 days) rats were fixed by a two-stage perfusion procedure employing Heidenhain's 'susa' solution. An equal number of rats were exposed to γ-irradiation at 6.5 R/day beginning on the 50th postnatal day and were sacrificed in the same manner and at the same age levels as the previous group. Paraffin sections were cut at 20 and 6 μ from cerebral cortical area 3 in the rat brains. Sections used for cell counts were stained with Harris' hematoxylin and eosin or iron hematoxylin, gallocyanin, acid fuchsin and ponceau de xylidene. Counts of neurons and glia were carried out at 20 equally spaced submolecular depth levels, and cell frequency profiles were plotted for each of the two cell types. The mean neuron and glial packing density for the total depth of the submolecular cortex of area 3 was not significantly different in young adult and middle-aged controls or in young adult irradiated (total dose 650 R) and control animals. However, statistical evaluation of data for relative depth levels 7 through 20 indicated that the packing density in this zone was significantly less (P<0.02) in middle-aged controls than in young adult animals. In middle-aged irradiated rats (total dose about 3250 R) neuron and glial packing densities for total depth of submolecular cortex were not significantly different than in control animals at the same age level. However, the values obtained for neuron packing density at relative depth levels 1 through 8 were significantly lower in middle-aged irradiated than in middle-aged control rats. The neuron packing density in middle-aged irradiated rats was significantly lower than in the young adult irradiated males. In electron micrographs, an increase in the amount of glycogen granules in astrocyte cell processes in cerebral cortex of irradiated middle-aged rats was noted, but there was no evidence of any other ultrastructural alterations

  10. Monkeying around with HIV vaccines: using rhesus macaques to define ‘gatekeepers’ for clinical trials

    OpenAIRE

    Shedlock, Devon J.; Silvestri, Guido; David B. Weiner

    2009-01-01

    Rhesus macaques are an important animal model for the study of human disease and the development of vaccines against HIV and AIDS. HIV vaccines have been benchmarked in rhesus macaque preclinical challenge studies using chimeric viruses made up of parts of HIV and simian immunodeficency viruses. However, the lack of efficacy in a recent clinical trial calls for a re-evaluation of the scientific assumptions regarding the predictive value of using data generated from rhesus macaques as a ‘gatek...

  11. Further evaluation of [11C]MP-10 as a radiotracer for phosphodiesterase 10A: PET imaging study in rhesus monkeys and brain tissue metabolite analysis.

    Science.gov (United States)

    Lin, Shu-Fei; Labaree, David; Chen, Ming-Kai; Holden, Daniel; Gallezot, Jean-Dominique; Kapinos, Michael; Teng, Jo-Ku; Najafzadeh, Soheila; Plisson, Christophe; Rabiner, Eugenii A; Gunn, Roger N; Carson, Richard E; Huang, Yiyun

    2015-02-01

    [(11)C]MP-10 is a potent and specific PET tracer previously shown to be suitable for imaging the phosphodiesterase 10A (PDE10A) in baboons with reversible kinetics and high specific binding. However, another report indicated that [(11)C]MP-10 displayed seemingly irreversible kinetics in rhesus monkeys, potentially due to the presence of a radiolabeled metabolite capable of penetrating the blood-brain-barrier (BBB) into the brain. This study was designed to address the discrepancies between the species by re-evaluating [(11)C]MP-10 in vivo in rhesus monkey with baseline scans to assess tissue uptake kinetics and self-blocking scans with unlabeled MP-10 to determine binding specificity. Ex vivo studies with one rhesus monkey and 4 Sprague-Dawley rats were also performed to investigate the presence of radiolabeled metabolites in the brain. Our results indicated that [(11)C]MP-10 displayed reversible uptake kinetics in rhesus monkeys, albeit slower than in baboons. Administration of unlabeled MP-10 reduced the binding of [(11)C]MP-10 in a dose-dependent manner in all brain regions including the cerebellum. Consequently, the cerebellum appeared not to be a suitable reference tissue in rhesus monkeys. Regional volume of distribution (VT) was mostly reliably derived with the multilinear analysis (MA1) method. In ex vivo studies in the monkey and rats only negligible amount of radiometabolites was seen in the brain of either species. In summary, results from the present study strongly support the suitability of [(11)C]MP-10 as a radiotracer for PET imaging and quantification of PDE10A in nonhuman primates. PMID:25450608

  12. Histopathologic findings of pulmonary acariasis in a rhesus monkeys breeding unit Aspectos histopatológicos da acaríase pulmonar em uma criação de macacos rhesus

    Directory of Open Access Journals (Sweden)

    Márcia Cristina R. Andrade

    2007-12-01

    Full Text Available Histological lesions in the lungs of rhesus monkeys (Macaca mulatta related with Pneumonyssus simicola were evidenced. The most prominent pathologic alterations included numerous thin-walled cysts 1-5 mm diameter scattered throughout the lungs, bronchiolitis, peribronchiolitis where the mites were found associated with pigmented and non-pigmented materials. Our study included data from 347 rhesus monkeys submitted to necropsies during 20 years. Four adult debilitated animals were found with pulmonary acariasis which showed a very low incidence of parasite (1.2% in the colony. Most of the published literature described as common and widespread pulmonary acariasis in Old World monkeys. The present study confirms the ubiquity of P. simicola in captive born and raised rhesus monkeys that would compromise experimental studies involving the respiratory system.Foram evidenciadas lesões histológicas nos pulmões de macacos rhesus (Macaca mulatta relacionadas ao Pneumonyssus simicola. As principais alterações incluíram numerosos cistos variando de 1-5 mm de diâmetro, com paredes finas e amplamente distribuídos nos pulmões; bronquiolite e peribronquiolite, onde os ácaros foram encontrados associados com materiais particulados pigmentados ou não. Nosso estudo incluiu dados de 347 macacos rhesus submetidos a necropsias no decorrer de 20 anos. A acaríase pulmonar foi diagnosticada em quatro animais adultos debilitados, o que representou uma incidência muito baixa do parasita (1,2% na colônia. A literatura descreve uma alta incidência de acaríase pulmonar em macacos do Velho Mundo. O presente estudo confirma a ubiqüidade do P. simicola em macacos rhesus nascidos e manejados em cativeiro, que compromete sua utilização em estudos experimentais envolvendo o sistema respiratório.

  13. Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Reed F. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States); Hammoud, Dima A. [Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Lackemeyer, Matthew G.; Yellayi, Srikanth [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States); Solomon, Jeffrey [Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Bohannon, Jordan K.; Janosko, Krisztina B.; Jett, Catherine; Cooper, Kurt [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States); Blaney, Joseph E. [Office of the Scientific Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Jahrling, Peter B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States); Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States)

    2015-07-15

    Cowpox virus (CPXV) inoculation of nonhuman primates (NHPs) has been suggested as an alternate model for smallpox (Kramski et al., 2010, PLoS One, 5, e10412). Previously, we have demonstrated that intrabronchial inoculation of CPXV-Brighton Red (CPXV-BR) into cynomolgus monkeys resulted in a disease that shared many similarities to smallpox; however, severe respiratory tract disease was observed (Smith et al., 2011, J. Gen. Virol.). Here we describe the course of disease after small particle aerosol exposure of rhesus monkeys using computed tomography (CT) to monitor respiratory disease progression. Subjects developed a severe respiratory disease that was uniformly lethal at 5.7 log{sub 10} PFU of CPXV-BR. CT indicated changes in lung architecture that correlated with changes in peripheral blood monocytes and peripheral oxygen saturation. While the small particle aerosol inoculation route does not accurately mimic human smallpox, the data suggest that CT can be used as a tool to monitor real-time disease progression for evaluation of animal models for human diseases. - Highlights: • Small particle aerosol exposure of rhesus results in a severe respiratory disease. • CT findings correlated with peripheral oxygen saturation and monocyte increases. • Virus dissemination was limited and mainly confined to the respiratory tract. • CT provides insight into pathogenesis to aid development of animal models of disease.

  14. X-ray-induced reciprocal translocations in stem-cell spermatogonia of the rhesus monkey: Dose and fractionation responses

    International Nuclear Information System (INIS)

    Rhesus monkeys received total body or local testes X-irradiation with unfractionated (50, 300, 400, 800 and 850 rad) or fractionated (200+200 rad with 24-h interval) exposures. At different times after irradiation, chromosomal analysis was made of C-banded dividing spermatocytes. The observed frequencies of translocation configurations confirmed earlier results about the low induction rate of reciprocal translocations in stem-cell spermatogonia of the rhesus monkey. The absence of any translocation induction at doses of 400 rad and higher indicates an extreme insensitivity of surviving radiation-resistant stem cells for the induction of this type of genetic damage. The frequency of translocations following a fractionated exposure to 400 rad, which is above the peak yield for single exposures, was clearly higher than that obtained when the same dose was applied as a single exposure (0.7 l versus 0%), but significantly lower than expected on the basis of additivity of the two fractions (0.71% versus 1.98%). (orig.)

  15. Protection from radiation-induced damage of spermatogenesis in the rhesus monkey (Macaca mulatta) by follicle-stimulating hormone

    International Nuclear Information System (INIS)

    In adult rhesus monkeys a two- to threefold increase in the number of spermatogonia was found at Day 75 after 1 Gy of X-irradiation when the animals were pretreated with two intramuscular injections of follicle-stimulating hormone (FSH) each day. Also the percentage of cross-sections of seminiferous tubules showing spermatogonia (repopulation index) was much higher when FSH was given before irradiation. At 75 days postirradiation the repopulation index was 39 +/- 10% after irradiation alone and 81 +/- 11% when FSH pretreatment was applied. The pretreatment with two injections of FSH each day during 16 days caused an increase in the number of proliferating A spermatogonia. In view of earlier results in the mouse, where proliferating spermatogonial stem cells appeared more radioresistant than quiescent ones, it is suggested that the protective effects of FSH treatment are caused by the increase in the proliferative activity of the A spermatogonia and consequently of the spermatogonial stem cells. The results indicate that in the rhesus monkey the maximal protective effect of FSH is reached after a period of treatment between 7 and 16 days

  16. Outbreak of Tuberculosis in a Colony of Rhesus Monkeys (Macaca mulatta) after Possible Indirect Contact with a Human TB Patient.

    Science.gov (United States)

    Mätz-Rensing, K; Hartmann, T; Wendel, G M; Frick, J S; Homolka, S; Richter, E; Munk, M H; Kaup, F-J

    2015-01-01

    Simian tuberculosis is one of the most important bacterial diseases of non-human primates. Outbreaks of tuberculosis have been reported in primate colonies almost as long as these animals have been used experimentally or kept in zoological gardens. Significant progress has been made in reducing the incidence of tuberculosis in captive non-human primates, but despite reasonable precautions, outbreaks continue to occur. The most relevant reason is the high incidence of tuberculosis (TB) amongst the human population, in which tuberculosis is regarded as an important re-emerging disease. Furthermore, many non-human primate species originate from countries with a high burden of human TB. Therefore, Mycobacterium tuberculosis remains a significant threat in animals imported from countries with high rates of human infection. We report an outbreak of tuberculosis among a group of rhesus monkeys (Macaca mulatta) living in a closed, long-term colony. The outbreak coincided with reactivation of a TB infection in a co-worker who never had direct access to the animal house or laboratories. Eleven of 26 rhesus monkeys developed classical chronic active tuberculosis with typical caseous granulomata of varying size within different organs. The main organ system involved was the lung, suggesting an aerosol route of infection. Such an outbreak has significant economic consequences due to animal loss, disruption of research and costs related to disease control. Precautionary measures must be improved in order to avoid TB in non-human primate colonies. PMID:26166434

  17. Autoradiographic localization of 3H-dihydrotestosterone in the preoptic area, hypothalamus, and amygdala of a male rhesus monkey

    International Nuclear Information System (INIS)

    In a preliminary study, autoradiography was used to localize target cells for 3H-dihydrotestosterone (DHT), a non-aromatizable androgen, in the brain of the rhesus monkey. One castrated male was injected intravenously with 2 mCi of 3H-DHT (0.42 μg/kg), and was killed one hour later. Neurons that concentrated radioactivity in their nuclei were located in widespread areas of the brain, which included the medial and suprachiasmatic preoptic nuclei, bed nucleus of the stria terminalis, lateral septal nucleus, anterior hypothalamic area, ventromedial, arcuate, dorsomedial, and paraventricular hypothalamic nuclei, ventral premammillary nucleus, and medial, cortical, basal accessory, and lateral amygdaloid nuclei. These results indicate that the topographic distribution of androgen target neurons is considerably wider than that observed in a study using 3H-testosterone (T) in the male rhesus monkey. However, further work is needed to elucidate these differences before attempting correlations between behavioral activity and androgen receptors in the brain

  18. Liver injury in rhesus monkeys subcutaneously injected with 2.3.7.8-tetrachlorodibenzo-p-dioxin

    Energy Technology Data Exchange (ETDEWEB)

    Tatsumi, Korenaga; Fukusato, Toshio [Teikyo Univ., Tokyo (Japan). School of Medicine; Kubota, Shunichiro; Ohta, Mari [Tokyo Univ. (Japan); Asaoka, Kazuo [Kyoto Univ., Aichi (Japan); Murata, Nobuo [Teikyo Univ., Kawasaki (Japan). Mizonokuchi Hospital, School of Medicine; Nomizu, Motoyoshi [Hokkaido Univ., Sapporo (Japan); Arima, Akihiro [Shin Nippon Biomedical Laboratories, Ltd., Kagoshima (Japan)

    2004-09-15

    2.3.7.8-tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic member of dioxins which are environmentally and biologically stable. Exposure to these compounds results in wide variety of effects including immunological dysfunction, tetragenecity and carcinogenesis. The liver is one of the central organs in which TCDD metabolized after absorption into the human and animal bodies. In experiments using rodents, TCDD accumulates and remains stable in the fatty tissues and liver for a long time. Kinetic profile of TCDD in our experiments using rhesus monkeys demonstrated the higher concentrations of TCDD in the fat, liver, and mammary gland. TCDD-induced liver injury in humans has been reported in Japan (PCB), Taiwan (PCB or PCDF), Italy (Sebeso, TCDD), and Vietnam (TCDD). Considerating the pronounced difference between species observed in some studies on non-human primates to assess effects of relatively low dose of TCDD, in the present study, liver injury in rhesus monkeys after a single subcutaneous administration of low dose of TCDD during pregnancy was investigated.

  19. Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease

    International Nuclear Information System (INIS)

    Cowpox virus (CPXV) inoculation of nonhuman primates (NHPs) has been suggested as an alternate model for smallpox (Kramski et al., 2010, PLoS One, 5, e10412). Previously, we have demonstrated that intrabronchial inoculation of CPXV-Brighton Red (CPXV-BR) into cynomolgus monkeys resulted in a disease that shared many similarities to smallpox; however, severe respiratory tract disease was observed (Smith et al., 2011, J. Gen. Virol.). Here we describe the course of disease after small particle aerosol exposure of rhesus monkeys using computed tomography (CT) to monitor respiratory disease progression. Subjects developed a severe respiratory disease that was uniformly lethal at 5.7 log10 PFU of CPXV-BR. CT indicated changes in lung architecture that correlated with changes in peripheral blood monocytes and peripheral oxygen saturation. While the small particle aerosol inoculation route does not accurately mimic human smallpox, the data suggest that CT can be used as a tool to monitor real-time disease progression for evaluation of animal models for human diseases. - Highlights: • Small particle aerosol exposure of rhesus results in a severe respiratory disease. • CT findings correlated with peripheral oxygen saturation and monocyte increases. • Virus dissemination was limited and mainly confined to the respiratory tract. • CT provides insight into pathogenesis to aid development of animal models of disease

  20. Relationship between discriminative stimulus effects and plasma methamphetamine and amphetamine levels of intramuscular methamphetamine in male rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L; Smith, Douglas A; Kisor, David F; Poklis, Justin L

    2016-02-01

    Methamphetamine is a globally abused drug that is metabolized to amphetamine, which also produces abuse-related behavioral effects. However, the contributing role of methamphetamine metabolism to amphetamine in methamphetamine's abuse-related subjective effects is unknown. This preclinical study was designed to determine 1) the relationship between plasma methamphetamine levels and methamphetamine discriminative stimulus effects and 2) the contribution of the methamphetamine metabolite amphetamine in the discriminative stimulus effects of methamphetamine in rhesus monkeys. Adult male rhesus monkeys (n=3) were trained to discriminate 0.18mg/kg intramuscular (+)-methamphetamine from saline in a two-key food-reinforced discrimination procedure. Time course of saline, (+)-methamphetamine (0.032-0.32mg/kg), and (+)-amphetamine (0.032-0.32mg/kg) discriminative stimulus effects were determined. Parallel pharmacokinetic studies were conducted in the same monkeys to determine plasma methamphetamine and amphetamine levels after methamphetamine administration and amphetamine levels after amphetamine administration for correlation with behavior in the discrimination procedure. Both methamphetamine and amphetamine produced full, ≥90%, methamphetamine-like discriminative stimulus effects. Amphetamine displayed a slightly, but significantly, longer duration of action than methamphetamine in the discrimination procedure. Both methamphetamine and amphetamine behavioral effects were related to methamphetamine and amphetamine plasma levels by a clockwise hysteresis loop indicating acute tolerance had developed to the discriminative stimulus effects. Furthermore, amphetamine levels after methamphetamine administration were absent when methamphetamine stimulus effects were greatest and peaked when methamphetamine discriminative stimulus effects returned to saline-like levels. Overall, these results demonstrate the methamphetamine metabolite amphetamine does not contribute to

  1. Three-dimensional organization of otolith-ocular reflexes in rhesus monkeys. III. Responses To translation

    Science.gov (United States)

    Angelaki, D. E.

    1998-01-01

    The three-dimensional (3-D) properties of the translational vestibulo-ocular reflexes (translational VORs) during lateral and fore-aft oscillations in complete darkness were studied in rhesus monkeys at frequencies between 0.16 and 25 Hz. In addition, constant velocity off-vertical axis rotations extended the frequency range to 0.02 Hz. During lateral motion, horizontal responses were in phase with linear velocity in the frequency range of 2-10 Hz. At both lower and higher frequencies, phase lags were introduced. Torsional response phase changed more than 180 degrees in the tested frequency range such that torsional eye movements, which could be regarded as compensatory to "an apparent roll tilt" at the lowest frequencies, became anticompensatory at all frequencies above approximately 1 Hz. These results suggest two functionally different frequency bandwidths for the translational VORs. In the low-frequency spectrum (frequency independent. At higher frequencies however, both horizontal and torsional response sensitivity and phase exhibit a similar frequency dependence, suggesting a common role during head translation. During up-down motion, vertical responses were in phase with translational velocity at 3-5 Hz but phase leads progressively increased for lower frequencies (>90 degrees at frequencies frequency response characteristics of the translational VORs were fitted by "periphery/brain stem" functions that related the linear acceleration input, transduced by primary otolith afferents, to the velocity signals providing the input to the velocity-to-position neural integrator and the oculomotor plant. The lowest-order, best-fit periphery/brain stem model that approximated the frequency dependence of the data consisted of a second order transfer function with two alternating poles (at 0.4 and 7.2 Hz) and zeros (at 0.035 and 3.4 Hz). In addition to clearly differentiator dynamics at low frequencies (less than approximately 0.5 Hz), there was no frequency bandwidth

  2. Radiolabeling human peripheral blood stem cells for positron emission tomography (PET imaging in young rhesus monkeys.

    Directory of Open Access Journals (Sweden)

    Alice F Tarantal

    Full Text Available These studies focused on a new radiolabeling technique with copper ((64Cu and zirconium ((89Zr for positron emission tomography (PET imaging using a CD45 antibody. Synthesis of (64Cu-CD45 and (89Zr-CD45 immunoconjugates was performed and the evaluation of the potential toxicity of radiolabeling human peripheral blood stem cells (hPBSC was assessed in vitro (viability, population doubling times, colony forming units. hPBSC viability was maintained as the dose of (64Cu-TETA-CD45 increased from 0 (92% to 160 µCi/mL (76%, p>0.05. Radiolabeling efficiency was not significantly increased with concentrations of (64Cu-TETA-CD45 >20 µCi/mL (p>0.50. Toxicity affecting both growth and colony formation was observed with hPBSC radiolabeled with ≥40 µCi/mL (p0.05, and a trend towards increased radiolabeling efficiency was noted as the dose of (89Zr-Df-CD45 increased, with a greater level of radiolabeling with 160 µCi/mL compared to 0-40 µCi/mL (p<0.05. A greater than 2,000 fold-increase in the level of (89Zr-Df-CD45 labeling efficiency was observed when compared to (64Cu-TETA-CD45. Similar to (64Cu-TETA-CD45, toxicity was noted when hPBSC were radiolabeled with ≥40 µCi/mL (p<0.05 (growth, colony formation. Taken together, 20 µCi/mL resulted in the highest level of radiolabeling efficiency without altering cell function. Young rhesus monkeys that had been transplanted prenatally with 25×10(6 hPBSC expressing firefly luciferase were assessed with bioluminescence imaging (BLI, then 0.3 mCi of (89Zr-Df-CD45, which showed the best radiolabeling efficiency, was injected intravenously for PET imaging. Results suggest that (89Zr-Df-CD45 was able to identify engrafted hPBSC in the same locations identified by BLI, although the background was high.

  3. The Macaque Social Responsiveness Scale (mSRS: A Rapid Screening Tool for Assessing Variability in the Social Responsiveness of Rhesus Monkeys (Macaca mulatta.

    Directory of Open Access Journals (Sweden)

    Eric J Feczko

    Full Text Available Understanding the biological mechanisms underlying human neuropsychiatric disorders, such as autism spectrum disorder (ASD, has been hindered by the lack of a robust, translational animal model. Rhesus monkeys (Macaca mulatta display many of the same social behaviors that are affected in ASD, making them an excellent animal species in which to model social impairments. However, the social impairments associated with ASD may reflect extreme ends of a continuous distribution of traits. Thus, to validate the rhesus monkey as an animal model for studying social impairments that has strong translational relevance for ASD, researchers need an easily-implemented measurement tool that can quantify variation in social behavior dimensionally. The Social Responsiveness Scale (SRS is a 65-item survey that identifies both typical and atypical social behaviors in humans that covary with ASD symptom severity. A chimpanzee SRS has already been validated and the current study adapted this tool for use in the rhesus monkey (mSRS. Fifteen raters completed the mSRS for 105 rhesus monkeys living at the Yerkes National Primate Research Center. The mSRS scores showed a unimodal distribution with a positive skew that identified 6 statistical outliers. Inter-rater reliability was very strong, but only 17 of the 36 questions showed positive intra-item reliability. The results of an exploratory factor analysis identified 3 factors that explained over 60% of the variance, with 12 items significantly loading onto the primary factor. These items reflected behaviors associated with social avoidance, social anxiety or inflexibility and social confidence. These initial findings are encouraging and suggest that variability in the social responsiveness of rhesus monkeys can be quantified using the mSRS: a tool that has strong translational relevance for human disorders. With further modification, the mSRS may provide an promising new direction for research on the biological

  4. The Macaque Social Responsiveness Scale (mSRS): A Rapid Screening Tool for Assessing Variability in the Social Responsiveness of Rhesus Monkeys (Macaca mulatta).

    Science.gov (United States)

    Feczko, Eric J; Bliss-Moreau, Eliza; Walum, Hasse; Pruett, John R; Parr, Lisa A

    2016-01-01

    Understanding the biological mechanisms underlying human neuropsychiatric disorders, such as autism spectrum disorder (ASD), has been hindered by the lack of a robust, translational animal model. Rhesus monkeys (Macaca mulatta) display many of the same social behaviors that are affected in ASD, making them an excellent animal species in which to model social impairments. However, the social impairments associated with ASD may reflect extreme ends of a continuous distribution of traits. Thus, to validate the rhesus monkey as an animal model for studying social impairments that has strong translational relevance for ASD, researchers need an easily-implemented measurement tool that can quantify variation in social behavior dimensionally. The Social Responsiveness Scale (SRS) is a 65-item survey that identifies both typical and atypical social behaviors in humans that covary with ASD symptom severity. A chimpanzee SRS has already been validated and the current study adapted this tool for use in the rhesus monkey (mSRS). Fifteen raters completed the mSRS for 105 rhesus monkeys living at the Yerkes National Primate Research Center. The mSRS scores showed a unimodal distribution with a positive skew that identified 6 statistical outliers. Inter-rater reliability was very strong, but only 17 of the 36 questions showed positive intra-item reliability. The results of an exploratory factor analysis identified 3 factors that explained over 60% of the variance, with 12 items significantly loading onto the primary factor. These items reflected behaviors associated with social avoidance, social anxiety or inflexibility and social confidence. These initial findings are encouraging and suggest that variability in the social responsiveness of rhesus monkeys can be quantified using the mSRS: a tool that has strong translational relevance for human disorders. With further modification, the mSRS may provide an promising new direction for research on the biological mechanisms underlying

  5. Effects of 50 MeV/sub d→ Be/ neutron irradiation on Rhesus monkey cervical spinal cord

    International Nuclear Information System (INIS)

    The cervical spinal cords of ten Rhesus monkeys were irradiated with 50 MeV/sub d → Be/ neutrons according to one of two dosage schedules: (1) 1300 rad/ sub nγ/ in nine fractions over 29 days, and (2) 1550 rad/sub nγ/ in nine fractions over 29 days. These doses are equivalent to 4000 rad/sub eq/ and 4800 rad/sub eq/, respectively, with 60Co using an RBE of 3.1 for late effects (conventional 200 rad per day fractionation). Whereas none of five monkeys that received a spinal cord dose of 1300 rad/sub nγ/ developed signs of neurologic dysfunction, all five animals that were irradiated to a dose of 1550 rad/sub nγ/ developed significant radiation myelitis. The histopathologic changes correlated well with the clinical observations. All of the animals that received 1550 rad/sub nγ/ exhibited severe malacia and moderate to severe demyelination of the white matter of the cervical spinal cord. The histopathologic changes in the monkeys irradiated with 1300 rad/sub nγ/ were minimal by comparison

  6. Effects of Odanacatib on bone mineralization density distribution in thoracic spine and femora of ovariectomized adult rhesus monkeys: a quantitative backscattered electron imaging study.

    Science.gov (United States)

    Fratzl-Zelman, Nadja; Roschger, Paul; Fisher, John E; Duong, Le T; Klaushofer, Klaus

    2013-03-01

    Odanacatib (ODN) has been developed as a selective inhibitor of cathepsin K, the major cysteine protease in osteoclasts. In adult rhesus monkeys, treatment with ODN prevents ovariectomy-induced bone loss in lumbar vertebrae and hip. In this study, we evaluate the effects of ODN on bone mineralization density distribution (BMDD) by quantitative backscattered electron imaging in vertebral spongiosa, distal femoral metaphyseal and cortical shaft from monkeys (aged 16-23 years), treated with vehicle (n=5) or ODN (6 mg/kg, n=4 or 30 mg/kg, n=4, PO daily) for 21 months. Dual-energy X-ray absorptiometry was measured in a subset of distal femoral samples. In lumbar vertebrae there was a shift to higher mineralization in samples from ODN-treated groups, compared to vehicle: CaMean (+4%), CaPeak (+3%), CaWidth (-9%), CaLow (-28%) in the 6 mg/kg group and CaMean (+5.1%, p<0.023), CaPeak (+3.4%, p<0.046), CaWidth (-15.7%, p=0.06) and CaLow (-38.2%, p<0.034) in the 30 mg/kg group. In distal femoral metaphyseal cancellous bone, there was a clear tendency toward a dose-dependent increase in matrix mineralization, as in the spine. However, primary and osteonal bone of the distal cortical diaphyses showed no significant change in BMDD, whereas bone mineral density was significantly increased after treatment. In ovariectomized monkeys, this study shows that ODN treatment increased trabecular BMDD, consistent with its previously reported ability to reduce cancellous remodeling. Here, ODN also showed no changes in BMDD in cortical bone sites, consistent with its actions on maintaining endocortical and stimulating periosteal bone formation. PMID:23179105

  7. Protection of rhesus monkeys from fatal Lassa fever by vaccination with a recombinant vaccinia virus containing the Lassa virus glycoprotein gene.

    Science.gov (United States)

    Fisher-Hoch, S P; McCormick, J B; Auperin, D; Brown, B G; Castor, M; Perez, G; Ruo, S; Conaty, A; Brammer, L; Bauer, S

    1989-01-01

    Lassa fever is an acute febrile disease of West Africa, where there are as many as 300,000 infections a year and an estimated 3000 deaths. As control of the rodent host is impracticable at present, the best immediate prospect is vaccination. We tested as potential vaccines in rhesus monkeys a closely related virus, Mopeia virus (two monkeys), and a recombinant vaccinia virus containing the Lassa virus glycoprotein gene, V-LSGPC (four monkeys). Two monkeys vaccinated with the New York Board of Health strain of vaccinia virus as controls died after challenge with Lassa virus. The two monkeys vaccinated with Mopeia virus developed antibodies measurable by radioimmunoprecipitation prior to challenge, and they survived challenge by Lassa virus with minimal physical or physiologic disturbances. However, both showed a transient, low-titer Lassa viremia. Two of the four animals vaccinated with V-LSGPC had antibodies to both Lassa glycoproteins, as determined by radioimmunoprecipitation. All four animals survived a challenge of Lassa virus but experienced a transient febrile illness and moderate physiologic changes following challenge. Virus was recoverable from each of these animals, but at low titer and only during a brief period, as observed for the Mopeia-protected animals. We conclude that V-LSGPC can protect rhesus monkeys against death from Lassa fever. PMID:2911575

  8. The archetype enhancer of simian virus 40 DNA is duplicated during virus growth in human cells and rhesus monkey kidney cells but not in green monkey kidney cells

    International Nuclear Information System (INIS)

    Archetype SV40, obtained directly from its natural host, is characterized by a single 72-bp enhancer element. In contrast, SV40 grown in cell culture almost invariably exhibits partial or complete duplication of the enhancer region. This distinction has been considered important in studies of human tumor material, since SV40-associated tumor isolates have been described having a single enhancer region, suggesting natural infection as opposed to possible contamination by laboratory strains of virus. However, the behavior of archetypal SV40 in cultured cells has never been methodically studied. In this study we reengineered nonarchetypal 776-SV40 to contain a single 72-bp enhancer region and used this reengineered archetypal DNA to transfect a number of simian and human cell lines. SV40 DNA recovered from these cells was analyzed by restriction endonuclease analysis, PCR, and DNA sequencing. Reengineered archetype SV40 propagated in green monkey TC-7 or BSC-1 kidney cells remained without enhancer region duplication even after extensive serial virus passage. Archetype SV40 grown in all but one of the rhesus or human cell lines initially appeared exclusively archetypal. However, when virus from these cell types was transferred to green monkey cells, variants with partial enhancer duplication appeared after as little as a single passage. These findings suggest (1) that virus with a single 72-bp enhancer may persist in cultured cells of simian and human origin; (2) that variants with partially duplicated enhancer regions may arise within cell lines in quantities below limits of detection; (3) that these variants may enjoy a selective advantage in cell types other than those from which they arose (e.g., green monkey kidney cells); and (4) that certain cell lines may support a selective growth advantage for the variants without supporting their formation. Our data indicate that enhancer duplication may also occur in human as well as rhesus kidney cells. Thus, detection of

  9. Ozone and allergen exposure during postnatal development alters the frequency and airway distribution of CD25+ cells in infant rhesus monkeys

    International Nuclear Information System (INIS)

    The epidemiologic link between air pollutant exposure and asthma has been supported by experimental findings, but the mechanisms are not understood. In this study, we evaluated the impact of combined ozone and house dust mite (HDM) exposure on the immunophenotype of peripheral blood and airway lymphocytes from rhesus macaque monkeys during the postnatal period of development. Starting at 30 days of age, monkeys were exposed to 11 cycles of filtered air, ozone, HDM aerosol, or ozone + HDM aerosol. Each cycle consisted of ozone delivered at 0.5 ppm for 5 days (8 h/day), followed by 9 days of filtered air; animals received HDM aerosol during the last 3 days of each ozone exposure period. Between 2-3 months of age, animals co-exposed to ozone + HDM exhibited a decline in total circulating leukocyte numbers and increased total circulating lymphocyte frequency. At 3 months of age, blood CD4+/CD25+ lymphocytes were increased with ozone + HDM. At 6 months of age, CD4+/CD25+ and CD8+/CD25+ lymphocyte populations increased in both blood and lavage of ozone + HDM animals. Overall volume of CD25+ cells within airway mucosa increased with HDM exposure. Ozone did not have an additive effect on volume of mucosal CD25+ cells in HDM-exposed animals, but did alter the anatomical distribution of this cell type throughout the proximal and distal airways. We conclude that a window of postnatal development is sensitive to air pollutant and allergen exposure, resulting in immunomodulation of peripheral blood and airway lymphocyte frequency and trafficking

  10. The role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in comparison with whole egg yolk for sperm cryopreservation in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    Qiao-Xiang Dong; Sarah E Rodenburg; Dana Hill; Catherine A VandeVoort

    2011-01-01

    Low-density lipoprotein (LDL) extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-density lipoprotein (HDL) in egg yolk may have a negative effect on post-thaw survival. The role of LDL and HDL in sperm cryopreservation of rhesus monkeys has not been explored. The present study evaluates their effect in comparison with egg yolk with or without the addition of permeable cryoprotectant (glycerol) on sperm cryopreservation of rhesus macaques. In addition, various additives intended to change the lipid composition of LDL-sperm membrane complex have also been tested for their effectiveness in preserving post-thaw viability. Our findings indicated that LDL is the main component in egg yolk that is responsible for its protective role for sperm cryopreservation in rhesus monkeys. Regardless of the presence or absence of glycerol, the protective role of LDL is similar to that of egg yolk and we did not observe any superiority in post-thaw survival with LDL when compared to egg yolk. Modifying the lipid composition of LDL-sperm membrane complex with the addition of cholesterol, cholesterol loaded cyclodextrin and phosphatidylcholine also did not yield any improvements in post-thaw survival; while addition of methyl-β-cyclodextrin reduced post-thaw motility. HDL plays a neutral role in sperm cryopreservation of rhesus monkeys. The present study suggests that egg yolk may still hold advantages when compared with LDL as effective components in extenders for sperm cryopreservation in rhesus monkeys.

  11. Evaluation of the Differences of Myocardial Fibers between Acute and Chronic Myocardial Infarction: Application of Diffusion Tensor Magnetic Resonance Imaging in a Rhesus Monkey Model

    Science.gov (United States)

    Wang, Yuqing; Cai, Wei; Wang, Lei; Xia, Rui; Chen, Wei; Zheng, Jie

    2016-01-01

    Objective To understand microstructural changes after myocardial infarction (MI), we evaluated myocardial fibers of rhesus monkeys during acute or chronic MI, and identified the differences of myocardial fibers between acute and chronic MI. Materials and Methods Six fixed hearts of rhesus monkeys with left anterior descending coronary artery ligation for 1 hour or 84 days were scanned by diffusion tensor magnetic resonance imaging (MRI) to measure apparent diffusion coefficient (ADC), fractional anisotropy (FA) and helix angle (HA). Results Comparing with acute MI monkeys (FA: 0.59 ± 0.02; ADC: 5.0 ± 0.6 × 10-4 mm2/s; HA: 94.5 ± 4.4°), chronic MI monkeys showed remarkably decreased FA value (0.26 ± 0.03), increased ADC value (7.8 ± 0.8 × 10-4mm2/s), decreased HA transmural range (49.5 ± 4.6°) and serious defects on endocardium in infarcted regions. The HA in infarcted regions shifted to more components of negative left-handed helix in chronic MI monkeys (-38.3 ± 5.0°–11.2 ± 4.3°) than in acute MI monkeys (-41.4 ± 5.1°–53.1 ± 3.7°), but the HA in remote regions shifted to more components of positive right-handed helix in chronic MI monkeys (-43.8 ± 2.7°–66.5 ± 4.9°) than in acute MI monkeys (-59.5 ± 3.4°–64.9 ± 4.3°). Conclusion Diffusion tensor MRI method helps to quantify differences of mechanical microstructure and water diffusion of myocardial fibers between acute and chronic MI monkey's models. PMID:27587961

  12. Development of a high-titer retrovirus producer cell line capable of gene transfer into rhesus monkey hematopoietic stem cells

    International Nuclear Information System (INIS)

    Retroviral-mediated gene transfer into primitive hematopoietic cells has been difficult to achieve in large-animal models. The authors have developed an amphotropic producer clone that generates >1010 recombinant retroviral particles (colony-forming units) per ml of culture medium. Autologous rhesus monkey bone marrow cells were cocultured with either high or low titer producer clones for 4-6 days and reinfused into sublethally irradiated animals. The proviral genome was detected in blood and bone-marrow cells from all three animals reconstituted with cells cocultured with the high-titer producer cells. In contrast, three animals reconstituted with bone marrow cocultured with the low-titer producer clone exhibited no evidence of gene transfer

  13. Effect of spaceflight on the isotonic contractile properties of single skeletal muscle fibers in the rhesus monkey

    Science.gov (United States)

    Fitts, R. H.; Romatowski, J. G.; Blaser, C.; De La Cruz, L.; Gettelman, G. J.; Widrick, J. J.

    2000-01-01

    Experiments from both Cosmos and Space Shuttle missions have shown weightlessness to result in a rapid decline in the mass and force of rat hindlimb extensor muscles. Additionally, despite an increased maximal shortening velocity, peak power was reduced in rat soleus muscle post-flight. In humans, declines in voluntary peak isometric ankle extensor torque ranging from 15-40% have been reported following long- and short-term spaceflight and prolonged bed rest. Complete understanding of the cellular events responsible for the fiber atrophy and the decline in force, as well as the development of effective countermeasures, will require detailed knowledge of how the physiological and biochemical processes of muscle function are altered by spaceflight. The specific purpose of this investigation was to determine the extent to which the isotonic contractile properties of the slow- and fast-twitch fiber types of the soleus and gastrocnemius muscles of rhesus monkeys (Macaca mulatta) were altered by a 14-day spaceflight.

  14. Evaluation of blood-brain barrier permeability changes in rhesus monkeys and man using 82Rb and positron emission tomography

    International Nuclear Information System (INIS)

    Dynamic positron tomography of the brain with /sup 82/Rb, obtained from a portable generator [/sup 82/Sr (25 days) - /sup 82/Rb (76 sec)], provides a means of studying blood-brain barrier (BBB) permeability in physiological and clinical investigations. The BBB in rhesus monkeys was opened unilaterally be intracarotid infusion of 3 M urea. This osmotic barrier opening allowed entry into the brain of intravenously administered rubidium chloride. The BBB opening was demonstrated noninvasively using /sup 82/Rb and positron emission tomography and corroborated by the accumulation of /sup 86/Rb in tissue samples. Positron emission tomography studies can be repeated every 5 min and indicate that dynamic tomography or static imaging can be used to study BBB permeability changes induced by a wide variety of noxious stimuli. Brain tumors in human subjects are readily detected because of the usual BBB permeability disruption in and around the tumors

  15. Evaluation of blood--brain barrier permeability changes in rhesus monkeys and man using 82Rb and positron emission tomography

    International Nuclear Information System (INIS)

    Dynamic positron tomography of the brain with 82Rb, obtained from a portable generator [82Sr (25 days) -- 82Rb (76 sec)], provides a means of studying blood-brain barrier (BBB) permeability in physiological and clinical investigations. The BBB in rhesus monkeys was opened unilaterally by intracarotid infusion of 3 M urea. This osmotic barrier opening allowed entry into the brain of intravenously administered rubidium chloride. The BBB opening was demonstrated noninvasively using 82Rb and positron emission tomography and corroborated by the accumulation of 86Rb in tissue samples. Positron emission tomography studies can be repeated every 5 min and indicate that dynamic tomography or static imaging can be used to study BBB permeability changes induced by a wide variety of noxious stimuli. Brain tumors in human subjects are readily detected because of the usual BBB permeability disruption in and around the tumors

  16. Note on hand use in the manipulation of joysticks by rhesus monkeys (Macaca mulatta) and chimpanzees (Pan troglodytes)

    Science.gov (United States)

    Hopkins, William D.; Washburn, David A.; Rumbaugh, Duane M.

    1989-01-01

    MacNeilage et al. (1987) have proposed that nonhuman primate handedness may be contingent on the specific task requirements, with visual-spatial tasks yielding left-hand preferences and fine-motor tasks producing right-hand preferences. This study reports hand preferences in the manipulation of joysticks by 2 rhesus monkeys and 3 chimpanzees. Reach data were also collected for comparison with preference data for manipulation of the joystick. The data indicated that all 5 subjects demonstrated significant right-hand preferences in manipulating the joystick. In contrast, no significant hand preferences were found for the reach data. Reaction-time data also indicated that the right hand could perform a perceptual-motor task better than the left hand in all 5 subjects. Overall, the data indicate that reach tasks may not be sensitive enough measures to produce reliable hand preferences, whereas tasks that assess fine-motor control produce significant hand preferences.

  17. Evidence for a partial deficiency of the LDL (apo B,E) receptor within a family of rhesus monkeys with a spontaneous hypercholesterolemia

    International Nuclear Information System (INIS)

    Spontaneous hypercholesterolemia is rare among non-human primates. Through screening of a rhesus monkey colony they have identified a family in which 3 out of its 6 members have a persistent hypercholesterolemia on a cholesterol-free Purina Chow diet and are high responders to a dietary fat challenge. On a basal diet the 3 affected animals also exhibited high plasma levels of LDL and apoB. To shed light on the mechanism of the hypercholesterolemia they have grown in culture fibroblasts from skin biopsies obtained from all members of the rhesus monkey family and 12 control. Binding studies at 40C and ligand blotting experiments using 125I-LDL of either normolipidemic rhesus monkeys or human subjects have shown that the fibroblasts from the 3 monkeys with a spontaneous hypercholesterolemia have a significant reduction of the number of LDL receptor and to the same extent as fibroblasts derived from subjects with heterozygous FH studied at the same time. The data suggest that the spontaneous elevation of plasma cholesterol observed in the 3 family members is related, at least in part, to a defective uptake of LDL by the LDL receptor pathway

  18. Dynamic Response-by-Response Models of Matching Behavior in Rhesus Monkeys

    Science.gov (United States)

    Lau, Brian; Glimcher, Paul W.

    2005-01-01

    We studied the choice behavior of 2 monkeys in a discrete-trial task with reinforcement contingencies similar to those Herrnstein (1961) used when he described the matching law. In each session, the monkeys experienced blocks of discrete trials at different relative-reinforcer frequencies or magnitudes with unsignalled transitions between the…

  19. Effects of several benzodiazepines, alone and in combination with flumazenil, in rhesus monkeys trained to discriminate pentobarbital from saline.

    Science.gov (United States)

    Woolverton, W L; Nader, M A

    1995-12-01

    The purpose of the present study was to further investigate the relationship between the DS effects of PB and those of benzodiazepines (BZs) and to begin to collect pharmacological information concerning receptor mechanisms involved in this behavioral effect of BZs. Rhesus monkeys (n = 3), trained to discriminate pentobarbital (PB; 10 mg/kg, IG) from saline under a discrete-trials shock avoidance procedure, were given IG diazepam (0.3-10 mg/kg), chlordiazepoxide (1.0-30 mg/kg), or etizolam (0.3-10 mg/kg) alone and in combination with flumazenil (0.01-1.7 mg/kg, IM). Flumazenil was administered 10 min prior to the administration of saline, PB or the BZs. All three BZs fully substituted for PB in all monkeys. Diazepam was the most potent with a mean ED50 of 0.81 mg/kg (SEM = 0.04) while chlordiazepoxide was the least potent (mean ED50 = 5.78 mg/kg, SEM = 1.22 mg/kg). The ED50 for etizolam was 1.22 mg/kg (SEM = 0.37 mg/kg). Pretreatment with flumazenil (0.01-1.0 mg/kg) resulted in a dose-related parallel shift to the right in the dose-response function for PB-appropriate responding in all monkeys for all three BZs. The mean (n = 3) pKB value with 0.1 mg/kg flumazenil was 6.51 (SEM = 0.42) for diazepam and 6.57 (SEM = 0.17) for chlordiazepoxide. This value could not be calculated for etizolam because only one monkey was tested with 0.1 mg/kg flumazenil. However, the mean pKB for etizolam considering all monkeys and all doses of flumazenil was 6.58 (SEM = 0.47). Apparent pA2 values for flumazenil with diazepam were 6.02 for one monkey and 7.11 for another. All three BZs tended to increase average latency to respond. Apparent pKB and pA2 analysis may prove useful for elucidating receptor mechanisms involved in the behavioral effects of BZs. PMID:8748392

  20. [18F]Fluoroazabenzoxazoles as potential amyloid plaque PET tracers: synthesis and in vivo evaluation in rhesus monkey

    International Nuclear Information System (INIS)

    Introduction: An 18F-labeled positron emission tomography (PET) tracer for amyloid plaque is desirable for early diagnosis of Alzheimer's disease, particularly to enable preventative treatment once effective therapeutics are available. Similarly, such a tracer would be useful as a biomarker for enrollment of patients in clinical trials for evaluation of antiamyloid therapeutics. Furthermore, changes in the level of plaque burden as quantified by an amyloid plaque PET tracer may provide valuable insights into the effectiveness of amyloid-targeted therapeutics. This work describes our approach to evaluate and select a candidate PET tracer for in vivo quantification of human amyloid plaque. Methods: Ligands were evaluated for their in vitro binding to human amyloid plaques, lipophilicity and predicted blood–brain barrier permeability. Candidates with favorable in vitro properties were radiolabeled with 18F and evaluated in vivo. Baseline PET scans in rhesus monkey were conducted to evaluate the regional distribution and kinetics of each tracer using tracer kinetic modeling methods. High binding potential in cerebral white matter and cortical grey matter was considered an unfavorable feature of the candidate tracers. Results: [18F]MK-3328 showed the most favorable combination of low in vivo binding potential in white matter and cortical grey matter in rhesus monkeys, low lipophilicity (Log D=2.91) and high affinity for human amyloid plaques (IC50=10.5±1.3 nM). Conclusions: [18F]MK-3328 was identified as a promising PET tracer for in vivo quantification of amyloid plaques, and further evaluation in humans is warranted.

  1. The Latency-Associated Nuclear Antigen of Rhesus Monkey Rhadinovirus Inhibits Viral Replication through Repression of Orf50/Rta Transcriptional Activation

    OpenAIRE

    DeWire, Scott M.; Damania, Blossom

    2005-01-01

    Rhesus monkey rhadinovirus (RRV) is a gamma-2-herpesvirus that is closely related to Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8. We have previously reported that the transcript for RRV latency-associated nuclear antigen (R-LANA) is expressed during lytic replication in rhesus fibroblasts. In this article, we report the development of a latent culture system for RRV and show that mRNA specific for R-LANA is expressed during latency as well. We have characterized the R-LANA pro...

  2. 正常猕猴与人的视网膜电图比较%The Comparation of the Electroretinogram (ERG) between Normal Rhesus Monkeys and Humans

    Institute of Scientific and Technical Information of China (English)

    夏峰; 安晶; 张磊; 刘锐; 张作明

    2012-01-01

    Objective To compare the difference between the electroretinogram (ERG) normal rhesus monkeys and humans, and provide a base for further study on the application of rhesus monkey retinal disease as an experiment model. Methods The electroretnogram (ERG) was recorded in 7 normal rhesus monkey (14 eyes) and 8 human (16 eyes). The recording items of ERG included rod response b wave, cone response, max response a and b waves, oscillatory potential 02, 30Hz flicker ERG 2P. The results were statistically tested. Results The ERG waveform results in rhesus monkey are similar to those in humans, but the amplitudes were decreased and the implicit times were prolonged compared with the humans, and the differences in the amplitude of the Cone ERG and the flicker ERG were not statistically significant. Conclusions The retinal function in rhesus monkey is quite similar to those in humans in the ERG recording. Rhesus monkey is a good animal model for the study on human retinal disease especially the macular.%目的 比较正常猕猴与人视网膜电图异同,为进一步利用猕猴建立动物模型研究视网膜疾病打下基础.方法 健康成年猕猴7只(14只眼)与8例(16只眼)正常人进行视网膜电图检测,对两者Rod-ERG中的b波,Max-ERG的a、b波,Cone-ERG的b波峰时值及波幅和OPs的O2值,Flicker-ERG的P值进行统计学检验.结果 猕猴与人的视网膜电图波形结果较为相似,各指标与人的结果相比,潜伏期短,幅值低,但Cone-ERG和FlickerERG两者幅值差异不具有统计学意义.结论 视网膜电图检测从功能上证明猕猴较其他常用实验动物更接近人,尤其表现在视锥细胞及黄斑区功能,可用作人类视网膜疾病尤其是黄斑区病变的良好动物模型.

  3. Rhesus monkey rhadinovirus (RRV): construction of a RRV-GFP recombinant virus and development of assays to assess viral replication

    International Nuclear Information System (INIS)

    Rhesus monkey rhadinovirus (RRV) is a γ-2-herpesvirus that is closely related to Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8). Lack of an efficient culture system to grow high titers of virus, and the lack of an in vivo animal model system, has hampered the study of KSHV replication and pathogenesis. RRV is capable of replicating to high titers on fibroblasts, thus facilitating the construction of recombinant rhadinoviruses. In addition, the ability to experimentally infect naieve rhesus macaques with RRV makes it an excellent model system to study γ-herpesvirus replication. Our study describes, for the first time, the construction of a GFP-expressing RRV recombinant virus using a traditional homologous recombination strategy. We have also developed two new methods for determining viral titers of RRV including a traditional viral plaque assay and a quantitative real-time PCR assay. We have compared the replication of wild-type RRV with that of the RRV-GFP recombinant virus in one-step growth curves. We have also measured the sensitivity of RRV to a small panel of antiviral drugs. The development of both the recombination strategy and the viral quantitation assays for RRV will lay the foundation for future studies to evaluate the contribution of individual genes to viral replication both in vitro and in vivo

  4. Occurrence of specific influenza antibodies in saliva and nasal secretion of monkeys (Macacus rhesus) after oral administration of influenza vaccine inactivated by gamma rays

    International Nuclear Information System (INIS)

    Antibodies in nasal secretion and saliva were measured in 10 Macacus rhesus wich had been immunized orally with a 60Co-gamma-inactivated influenza vaccine. Prior to immunization monkeys had no detectable antibodies against hemagglutinin (HA) and neuraminidase, resp. in sera or secretions. Oral immunization using intraoesophageal tubing, induced the occurrence of both antiobodies in pilocarpine-stimulated secretions within 28 days but not in sera. 6 monkeys reacted with increasing HA antibodies in nasal secretions and 10 monkeys with increasing neuraminidase antibodies. Salivary HA antibodies occurred in 8 of 10 and neuraminidase antibodies in 9 of 10 animals. In most cases antibodies occurred in both secretions simultaneously. These results demonstrate the stimulation of antibodies specific to influenza in the respiratory tract of monkeys after oral immunization with an inactivated vaccine, for the first time. (author)

  5. Analysis of the Intestinal Pathological Changes in Dead Rhesus Monkeys Bred under Captive Conditions%人工饲养条件下死亡实验恒河猴肠道病理改变特点分析

    Institute of Scientific and Technical Information of China (English)

    赵玺龙; 杨举伦; 宋蜀伶; 徐文漭; 潘鑫艳; 黎贵芸; 李锋

    2011-01-01

    目的 观察人工饲养条件下实验恒河猴肠道病理改变,探讨实验猴肠道疾病分布规律和病理改变特点,丰富实验猴自发病变基本研究资料.方法 对1998 ~2008年云南地区饲养的自然死亡的155只恒河猴(年龄2~20岁)的肠道进行病理检查,按年龄分为幼年组、成年组、老年组,并对观察结果进行统计学分析.结果 155例恒河猴中58例检出肠道病变,有慢性肠炎、急性肠炎、黏膜充血水肿、出血、糜烂、溃疡、穿孔、寄生虫共8种主要病变,出现率最高的为急性肠炎(20.00%).实验猴不同年龄组肠道病变类型分布基本相同,肠道病变率随年龄增长而增高,不同年龄组间统计学分析差异无显著性.结论 人工饲养条件下死亡实验猴肠道病变检出率较高,急性肠炎是实验猴的主要致死原因之一,实验猴肠道病理改变随年龄增长而病变加重.对实验猴饲养和研究时,应重视肠道病变因素,尤其是急性肠炎.死亡实验猴肠道病变研究对实验猴的质量控制和相关动物实验有重要指导价值.%Objective To observe the intestinal pathological changes of dead rhesus monkeys bred under captive conditions, and to explore the rule of distribution of characteristic pathological changes. Methods One hundred and fiftyfive naturally died monkeys in the age of 2 to 20 years, bred in institutes in Yunnan province, were autopsied from 1998 to 2008. The monkeys were divided into young, adult and old groups according to their age. The intestinal changes were investigated by routine histopathological examination and analysis by chi-square test. Results Of the 155 monkeys, 58 animals had intestinal lesions (37.42%). The main lesions included chronic enteritis, acute enteritis, bleeding and erosion, ulcers, perforation, parasite infections and others. All kinds of intestinal lesions occurred in the 3 age groups. Among these lesions the incidence rate of acute enteritis is the

  6. Acute respiratory bronchiolitis: an ultrastructural and autoradiographic study of epithelial cell injury and renewal in Rhesus monkeys exposed to ozone

    International Nuclear Information System (INIS)

    The pathogenesis of acute respiratory bronchiolitis was examined in Rhesus monkeys exposed to 0.8 ppM ozone for 4 to 50 hours. Epithelial injury and renewal were qualitatively and quantitatively characterized by correlated techniques of scanning and transmission electron microscopy as well as by light-microscopic autoradiography following labeling with tritiated thymidine. Extensive degeneration and necrosis of Type 1 epithelial cells occurred on the respiratory bronchiolar wall during the initial 4 to 12 hours of exposure. Increased numbers of labeled epithelial cells were present in this region after 18 hours of exposure, and the highest labeling index (18%) was measured after 50 hours of exposure. Most (67 to 80%) of the labeled cells and all the mitotic epithelial cells (22) observed ultrastructurally were cuboidal bronchiolar epithelial cells. Of the labeled epithelial cells, 20 to 33% were Type 2 epithelial cells. After 50 hours of exposure the respiratory bronchiolar epithelium was hyperplastic. The predominant inflammatory cell in respiratory bronchiolar exudate was the alveolar macrophage. Monkeys that were exposed for 50 hours and allowed to recover in unozonized air for 7 days had incomplete resolution of respiratory bronchiolar epithelial hyperplasia. The results indicate that Type 1 epithelial cells lining respiratory bronchioles are the cell types most sensitive to injury and that both cuboidal bronchiolar epithelial cells and Type 2 epithelial cells function as stem cells in epithelial renewal

  7. Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease.

    Science.gov (United States)

    Johnson, Reed F; Hammoud, Dima A; Lackemeyer, Matthew G; Yellayi, Srikanth; Solomon, Jeffrey; Bohannon, Jordan K; Janosko, Krisztina B; Jett, Catherine; Cooper, Kurt; Blaney, Joseph E; Jahrling, Peter B

    2015-07-01

    Cowpox virus (CPXV) inoculation of nonhuman primates (NHPs) has been suggested as an alternate model for smallpox (Kramski et al., 2010, PLoS One, 5, e10412). Previously, we have demonstrated that intrabronchial inoculation of CPXV-Brighton Red (CPXV-BR) into cynomolgus monkeys resulted in a disease that shared many similarities to smallpox; however, severe respiratory tract disease was observed (Smith et al., 2011, J. Gen. Virol.). Here we describe the course of disease after small particle aerosol exposure of rhesus monkeys using computed tomography (CT) to monitor respiratory disease progression. Subjects developed a severe respiratory disease that was uniformly lethal at 5.7 log10 PFU of CPXV-BR. CT indicated changes in lung architecture that correlated with changes in peripheral blood monocytes and peripheral oxygen saturation. While the small particle aerosol inoculation route does not accurately mimic human smallpox, the data suggest that CT can be used as a tool to monitor real-time disease progression for evaluation of animal models for human diseases. PMID:25776759

  8. Similarities in the immunoglobulin response and VH gene usage in rhesus monkeys and humans exposed to porcine hepatocytes

    Directory of Open Access Journals (Sweden)

    Borie Dominic C

    2006-03-01

    Full Text Available Abstract Background The use of porcine cells and organs as a source of xenografts for human patients would vastly increase the donor pool; however, both humans and Old World primates vigorously reject pig tissues due to xenoantibodies that react with the polysaccharide galactose α (1,3 galactose (αGal present on the surface of many porcine cells. We previously examined the xenoantibody response in patients exposed to porcine hepatocytes via treatment(s with bioartficial liver devices (BALs, composed of porcine cells in a support matrix. We determined that xenoantibodies in BAL-treated patients are predominantly directed at porcine αGal carbohydrate epitopes, and are encoded by a small number of germline heavy chain variable region (VH immunoglobulin genes. The studies described in this manuscript were designed to identify whether the xenoantibody responses and the IgVH genes encoding antibodies to porcine hepatocytes in non-human primates used as preclinical models are similar to those in humans. Adult non-immunosuppressed rhesus monkeys (Macaca mulatta were injected intra-portally with porcine hepatocytes or heterotopically transplanted with a porcine liver lobe. Peripheral blood leukocytes and serum were obtained prior to and at multiple time points after exposure, and the immune response was characterized, using ELISA to evaluate the levels and specificities of circulating xenoantibodies, and the production of cDNA libraries to determine the genes used by B cells to encode those antibodies. Results Xenoantibodies produced following exposure to isolated hepatocytes and solid organ liver grafts were predominantly encoded by genes in the VH3 family, with a minor contribution from the VH4 family. Immunoglobulin heavy-chain gene (VH cDNA library screening and gene sequencing of IgM libraries identified the genes as most closely-related to the IGHV3-11 and IGHV4-59 germline progenitors. One of the genes most similar to IGHV3-11, VH3-11cyno, has

  9. Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Wong Brian A

    2005-10-01

    Full Text Available Abstract Background Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation. Methods Subchronic (6 hr/day, 5 days/week inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4–6 animals/exposure concentration was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m3 for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m3 for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point was exposed to manganese sulfate at 1.5 mg Mn/m3 and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett's multiple comparison. Histopathological findings were evaluated using a Pearson's Chi-Square test. Results Animals exposed to manganese sulfate at ≥0.3 mg Mn/m3 for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m3 for ≥15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure. Conclusion High-dose subchronic manganese sulfate inhalation is

  10. SHIV-1157i and passaged progeny viruses encoding R5 HIV-1 clade C env cause AIDS in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Siddappa Nagadenahalli B

    2008-10-01

    Full Text Available Abstract Background Infection of nonhuman primates with simian immunodeficiency virus (SIV or chimeric simian-human immunodeficiency virus (SHIV strains is widely used to study lentiviral pathogenesis, antiviral immunity and the efficacy of AIDS vaccine candidates. SHIV challenges allow assessment of anti-HIV-1 envelope responses in primates. As such, SHIVs should mimic natural HIV-1 infection in humans and, to address the pandemic, encode HIV-1 Env components representing major viral subtypes worldwide. Results We have developed a panel of clade C R5-tropic SHIVs based upon env of a Zambian pediatric isolate of HIV-1 clade C, the world's most prevalent HIV-1 subtype. The parental infectious proviral clone, SHIV-1157i, was rapidly passaged through five rhesus monkeys. After AIDS developed in the first animal at week 123 post-inoculation, infected blood was infused into a sixth monkey. Virus reisolated at this late stage was still exclusively R5 tropic and mucosally transmissible. Here we describe the long-term follow-up of this initial cohort of six monkeys. Two have remained non-progressors, whereas the other four gradually progressed to AIDS within 123–270 weeks post-exposure. Two progressors succumbed to opportunistic infections, including a case of SV40 encephalitis. Conclusion These data document the disease progression induced by the first mucosally transmissible, pathogenic R5 non-clade B SHIV and suggest that SHIV-1157i-derived viruses, including the late-stage, highly replication-competent SHIV-1157ipd3N4 previously described (Song et al., 2006, display biological characteristics that mirror those of HIV-1 clade C and support their expanded use for AIDS vaccine studies in nonhuman primates.

  11. Methamphetamine-like discriminative stimulus effects of bupropion and its two hydroxy metabolites in male rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L; Smith, Douglas A; Blough, Bruce E

    2016-04-01

    The dopamine transporter (DAT) inhibitor and nicotinic acetylcholine (nACh) receptor antagonist bupropion is being investigated as a candidate 'agonist' medication for methamphetamine addiction. In addition to its complex pharmacology, bupropion also has two distinct pharmacologically active metabolites. However, the mechanism by which bupropion produces methamphetamine-like 'agonist' effects remains unknown. The aim of the present study was to determine the role of DAT inhibition, nACh receptor antagonism, and the hydroxybupropion metabolites in the methamphetamine-like discriminative stimulus effects of bupropion in rhesus monkeys. In addition, varenicline, a partial agonist at the nACh receptor, and risperidone, a dopamine antagonist, were tested as controls. Monkeys (n=4) were trained to discriminate 0.18 mg/kg intramuscular methamphetamine from saline in a two-key food-reinforced discrimination procedure. The potency and time course of methamphetamine-like discriminative stimulus effects were determined for all compounds. Bupropion, methylphenidate, and 2S,3S-hydroxybupropion produced full, at least 90%, methamphetamine-like effects. 2R,3R-Hydroxybupropion, mecamylamine, and nicotine also produced full methamphetamine-like effects, but drug potency was more variable between monkeys. Varenicline produced partial methamphetamine-like effects, whereas risperidone did not. Overall, these results suggest DAT inhibition as the major mechanism of the methamphetamine-like 'agonist' effects of bupropion, although nACh receptor antagonism appeared, at least partially, to contribute. Furthermore, the contribution of the 2S,3S-hydroxybupropion metabolite could not be completely ruled out. PMID:26886209

  12. Hyperinsulinemia/diabetes, hearing, and aging in the University of Wisconsin calorie restriction monkeys.

    Science.gov (United States)

    Fowler, Cynthia G; Chiasson, Kirstin Beach; Colman, Ricki J; Kemnitz, Joseph W; Beasley, T Mark; Weindruch, Richard H

    2015-10-01

    The purpose of this study was to determine the effects of hyperinsulinemia/Type 2 diabetes mellitus (HI-T2DM) on hearing impairment using rhesus monkeys to obtain control over diet and lifestyle factors that confound human studies. The study is a retrospective evaluation of rhesus monkeys from the Wisconsin National Primate Research Center (WNPRC) study on caloric restriction and aging. The research questions were the following: 1. Is HI-T2DM related to hearing impairment? 2. If so, what is the site of lesion in the auditory system? and 3. What physiological factors affect the risk of hearing loss in HI-T2DM? Three groups of eight monkeys each were matched by sex and age; the caloric restricted (CR) monkeys had a reduced risk of diabetes, the normal control (NL) group had a normal risk, and the hyperinsulinemia/diabetes (HI-D) group had already developed HI-T2DM. Auditory testing included distortion product otoacoustic emissions (DPOAEs) with f2 frequencies from 2211 to 8837 Hz and auditory brainstem responses (ABRs) obtained with clicks and tone bursts (8, 16, and 32 kHz). DPOAEs had signal-to-noise ratios 8-17 dB larger in the NL group than in the HI-D and CR groups, signifying that cochlear function was best in the NL group. ABR thresholds were 5-8 dB better in the NL group than in the HI-D group, although no significant differences across the groups were evident for the thresholds, latencies, interwave intervals, or amplitudes. Correlations were significant for quadratic relations between body mass index (BMI) and DPOAE, with largest DPOAEs for animals in the middle of the BMI range. ABR thresholds elicited with 16 and 32 kHz signals were significantly correlated, positively with BMI and HbA1c, and negatively with KG (glucose tolerance), SI (insulin sensitivity index) and DI (disposition index). These findings suggest that the hearing loss associated with HI-T2DM is predominantly cochlear, and auditory structures underlying the higher frequencies are at

  13. Antagonism of Corticotrophin-Releasing Factor Type 1 Receptors Attenuates Caloric Intake of Free Feeding Subordinate Female Rhesus Monkeys in a Rich Dietary Environment

    OpenAIRE

    Moore, C. J.; Johnson, Z P; Higgins, M.; Toufexis, D; Wilson, M E

    2014-01-01

    Social subordination in macaque females is a known chronic stressor and previous studies have shown that socially subordinate female rhesus monkeys consume fewer kilocalories than dominant animals when a typical laboratory chow diet is available. However, in a rich dietary environment that provides access to chow in combination with a more palatable diet (i.e. high in fat and refined sugar), subordinate animals consume significantly more daily kilocalories than dominant conspecifics. Substant...

  14. Recombinant interferon-alpha2b poly(lactic-co-glycolic acid) microspheres: pharmacokinetics.pharmacodynamics study in rhesus monkeys following intramuscular administration

    Institute of Scientific and Technical Information of China (English)

    Yong-ming ZHANG; Fan YANG; Yi-qun YANG; Feng-lan SONG; An-long XU

    2008-01-01

    Aim: Investigation into pharmacokinetic-pharmacodynamic properties of interferon-alpha (IFN-α)2b-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) in rhesus monkey primates. Method: IFN-α2b was loaded with biodegradable PLGA with 3 inherent viscosities using a double emulsion and solvent evaporation method. The particle size, surface morphology, and in vitro release profiles were investigated. Two groups of rhesus monkeys (n=3) were injected intramuscularly with either 3 MIU/kg commercial IFN-a2b lyophilized powder or IFN-α2b-loaded PLGA microspheres (inherent viscosity of 0.89 dL/g). In vitro release was determined by Lowry protein assay. The serum IFN and neopterin levels were determined by the enzyme-linked immunosorbent assay (ELISA) method to evaluate biological activity of the microspheres in rhesus monkeys. Results: The IFN-α2b microspheres with 3 inherent viscosities (0.39, 0.89, and 1.13 dL/g) were entirely spherical and had a smooth surface. The average diameter of each type was 45.55, 81.23, and 110.25 μm, respectively. The in vitro release was 30 d. The pharmacokinetic-pharmacodynamic properties between the IFN-α2b microspheres and IFN-α2b lyophilized powder were significantly different (P<0.05). Conclusion: The drug residence time for the IFN-α2b of the PLGA microsphere with an inherent viscosity of 0.89 dL/g in plasma significantly increased and had a longer time of biological effects in rhesus monkeys following intramuscular administration.

  15. The Macaque Social Responsiveness Scale (mSRS): A Rapid Screening Tool for Assessing Variability in the Social Responsiveness of Rhesus Monkeys (Macaca mulatta)

    OpenAIRE

    Feczko, Eric J.; Eliza Bliss-Moreau; Hasse Walum; Pruett, John R.; Parr, Lisa A.

    2016-01-01

    Understanding the biological mechanisms underlying human neuropsychiatric disorders, such as autism spectrum disorder (ASD), has been hindered by the lack of a robust, translational animal model. Rhesus monkeys (Macaca mulatta) display many of the same social behaviors that are affected in ASD, making them an excellent animal species in which to model social impairments. However, the social impairments associated with ASD may reflect extreme ends of a continuous distribution of traits. Thus, ...

  16. Intra-amniotic IL-1β induces fetal inflammation in rhesus monkeys and alters the regulatory T cell/IL-17 balance

    OpenAIRE

    Kallapur, Suhas G.; Presicce, Pietro; Senthamaraikannan, Paranthaman; Alvarez, Manuel; Tarantal, Alice F; Miller, Lisa M.; Jobe, Alan H.; Chougnet, Claire A.

    2013-01-01

    Very low birth weight preterm newborns are susceptible to the development of debilitating inflammatory diseases, many of which are associated with chorioamnionitis. To define the effects of chorioamnionitis on the fetal immune system, IL-1β was administered intra-amniotically at ∼80% gestation in rhesus monkeys. IL-1β caused histological chorioamnionitis as well as lung inflammation (infiltration of neutrophils or monocytes in the fetal airways). There were large increases of multiple pro-inf...

  17. Behavioral Inhibition in Rhesus Monkeys (Macaca mulatta) Is Related to the Airways Response, but Not Immune Measures, Commonly Associated with Asthma

    OpenAIRE

    Katie Chun; Lisa A Miller; Schelegle, Edward S.; Hyde, Dallas M.; Capitanio, John P.

    2013-01-01

    Behavioral inhibition reflects a disposition to react warily to novel situations, and has been associated with atopic diseases such as asthma. Retrospective work established the relationship between behavioral inhibition in rhesus monkeys (Macaca mulatta) and airway hyperresponsiveness, but not atopy, and the suggestion was made that behavioral inhibition might index components of asthma that are not immune-related. In the present study, we prospectively examined the relationship between beha...

  18. Identification of major urinary metabolites of nafarelin acetate, a potent agonist of luteinizing hormone-releasing hormone, in the rhesus monkey

    International Nuclear Information System (INIS)

    Nafarelin acetate (less than Glu-His-Trp-Ser-Tyr-3-(2-naphthyl)-D-Ala-Leu-Arg-Pro-Gly-NH2) is a potent agonistic analogue of luteinizing hormone-releasing hormone. After a single iv administration of nafarelin acetate (with 14C label at C-3 of 3-(2-naphthyl)-D-Ala) to female rhesus monkeys, about 80% of the radioactivity was eliminated in urine. Five major radioactive urinary metabolites were isolated and purified by reversed phase HPLC. Four of these metabolites, identified by amino acid analysis, were short peptides: the 5-10-hexapeptide amide, the 6-10-pentapeptide amide, the 5-7-tripeptide, and the 6-7-dipeptide. The fifth metabolite, which accounted for about 15% of the radioactivity administered, was shown by NMR and mass spectrometry to be 2-naphthylacetic acid. A possible pathway of its formation is by oxidative deamination of 3-(2-napthyl)-D-Ala to give the corresponding alpha-keto acid, followed by oxidative decarboxylation of the alpha-keto acid. These five metabolites together accounted for about 70% of the radioactivity recovered in the urine of rhesus monkeys, or more than half of the radioactivity in the administered dose. Nafarelin acetate was also present in small amounts. Several of these metabolites were also present in plasma of the rhesus monkey

  19. Estudo comparativo das inclusões do alastrim e da vacina no macaco (Macacus rhesus A comparison of the inclusion bodies of alastrim and vaccinia in the monkey (Macacus rhesus

    Directory of Open Access Journals (Sweden)

    C. Magarinos Torres

    1934-02-01

    Full Text Available Vesiculas e pustulas contendo numerosas inclusões citoplasmicas nas celulas epidermicas, foram regularmente produzidas no macaco (Macacus rhesus, quer com o virus do alastrim, quer com o da vacina, após inoculação endovenosa e sem previa escarificação. O virus do alastrim parece menos virulento para essa especie de macaco que o da vacina. Ao passo que 12 macacos rhesus injetados por via endovenosa com sete amostras diferentes de virus do alastrim, após apresentarem com regularidade um infecção experimental, sobreviveram e se conservaram em boa saúde, a injecção endovenosa do virus da vacina recentemente preparado (polpa bruta produziu a morte em 2, dentre 4 animais experimentados. 2. - Foram notadas diferenças pequenas, mas nitidas, na morfologia das inclusões do alastrim e da vacina, em material fixado no liquido de Helly, incluido em parafina e corado pela hematoxilina-eosina. Dizem elas respeito ao numero de inclusões encontradas em cada celula epidermica e às suas reações de coloração. 3. - As inclusões do alastrim, quando apresentam grandes dimensões, conservam-se unicas ou solitarias no citoplasma das celulas epidermicas do macaco rhesus, e coram-se em tonalidade que varia do azul escuro ao cinzento-azulado. Comtudo, em celulas que sofreram necrose, ou naquelas contendo 2 a 4 inclusões de pequenas dimensões, por vezes elas se mostram coradas em roseo. 4. - As inclusões da vacina, quando em faze adeantada de desenvolvimento, são multiplas nas celulas epidermicas do macaco rhesus e mostram, regularmente, uma policromatofilia caracteristica.1. - Vesicles and pustules containing numerous cytoplasmic inclusion bodies within the epidermal cells were regularly produced in monkeys (Macacus rhesus by intravenous inoculation either of alastrim virus or of recently prepared vaccine emulsion, no previous scarifications being required. Alastrim virus seems less virulent for this species of monkey than the virus of vaccinia is

  20. Transplantation of adult monkey neural stem cells into a contusion spinal cord injury model in rhesus macaque monkeys

    DEFF Research Database (Denmark)

    Nemati, Shiva Nemati; Jabbari, Reza; Hajinasrollah, Mostafa;

    2014-01-01

    confirmed by magnetic resonance imaging (MRI) and histological analysis. Animals were clinically observed for 6 months. RESULTS: Analysis confirmed homing of mNSCs into the injury site. Transplanted cells expressed neuronal markers (TubIII). Hind limb performance improved in trans- planted animals based on......, therefore, to explore the efficacy of adult monkey NSC (mNSC) in a primate SCI model. MATERIALS AND METHODS: In this experimental study, isolated mNSCs were analyzed by flow cytometry, immunocytochemistry, and RT-PCR. Next, BrdU-labeled cells were transplanted into a SCI model. The SCI animal model was......OBJECTIVE: Currently, cellular transplantation for spinal cord injuries (SCI) is the subject of numerous preclinical studies. Among the many cell types in the adult brain, there is a unique subpopulation of neural stem cells (NSC) that can self-renew and differentiate into neurons. The study aims...

  1. Neonatal face-to-face interactions promote later social behaviour in infant rhesus monkeys

    Science.gov (United States)

    Dettmer, Amanda M.; Kaburu, Stefano S. K.; Simpson, Elizabeth A.; Paukner, Annika; Sclafani, Valentina; Byers, Kristen L.; Murphy, Ashley M.; Miller, Michelle; Marquez, Neal; Miller, Grace M.; Suomi, Stephen J.; Ferrari, Pier F.

    2016-01-01

    In primates, including humans, mothers engage in face-to-face interactions with their infants, with frequencies varying both within and across species. However, the impact of this variation in face-to-face interactions on infant social development is unclear. Here we report that infant monkeys (Macaca mulatta) who engaged in more neonatal face-to-face interactions with mothers have increased social interactions at 2 and 5 months. In a controlled experiment, we show that this effect is not due to physical contact alone: monkeys randomly assigned to receive additional neonatal face-to-face interactions (mutual gaze and intermittent lip-smacking) with human caregivers display increased social interest at 2 months, compared with monkeys who received only additional handling. These studies suggest that face-to-face interactions from birth promote young primate social interest and competency. PMID:27300086

  2. Effects of Permanent Separation from Mother on Infant Monkeys

    Science.gov (United States)

    Suomi, Stephen; And Others

    1973-01-01

    A study designed to investigate the effects of permanent maternal separation in infant rhesus monkeys, 60, 90, and 120 days of age, and housed individually or in Paris. Monkeys separated at 90 days and housed individually showed the highest levels of disturbance. (DP)

  3. In vitro effect of the lethal antibody on schistosomula in sera of rhesus monkeys immunized with highly x-irradiated cercariae. [Schistosoma mansoni, S. japonicum

    Energy Technology Data Exchange (ETDEWEB)

    Li Hs' u, S.Y.; Hs' u, H.F.; Isacson, P.; Kremenak, B.W.; Cheng, H.F.

    1976-12-01

    The in vitro effect of the lethal antibody on schistosomula in sera of rhesus monkeys immunized with highly x-irradiated cercariae of Schistosoma mansoni or S. japonicum was studied. In all 6 experimental monkeys, 4 unchallenged and 2 challenged, the effects of lethal antibody on schistosomula were demonstrated. The sera of the challenged monkeys had no stronger lethal effect than those of the unchallenged monkeys. This shows that the lethal antibody can be produced by the antigenic stimulation of schistosomula alone. The mortality rates of schistosomula in immune sera were already high at day 1, increased to a certain extent from day 1 to day 4, but showed no significant further increase in days 5 and 6. Two kinds of immunological reactions were observed: perischistosomular precipitate (PSP) and perischistosomular envelope (PSE). Schistosomula surrounded with PSP were usually dying or dead and those enclosed in PSE were usually alive and motile. Thus PSP may be related with the lethal antibody and PSE with a kind of enhancing antibody. Schistosomula with PSP showed a positive fluorescent reaction when stained with fluorescein-labeled rabbit anti-rhesus IgG. Scanning electron micrographs of schistosomula with PSP showed a highly degenerated tegument. These facts indicate that the antibody in PSP contains a fraction of IgG which acts on the tegument of schistosomula.

  4. A New Advancement in Animal Model(Rhesus Monkey)of Human Early Adversity%人类早期应激猕猴模型新进展

    Institute of Scientific and Technical Information of China (English)

    冯晓丽; 胡新天

    2012-01-01

    母婴分离常常被用来模拟人类早期应激,但它对个体的负面影响能否被长期正常的生活经历所逆转仍然未知.本研究考察了母婴分离猕猴经历了长期的正常社会生活之后的HPA轴功能和行为.结果发现,母婴分离猴的HPA轴功能紊乱,行为异常,尤其是反映焦虑状态的行为大大增加.从而第一次在猕猴中证明,母婴分离的影响是长期和持久的.同时也说明母婴分离猕猴是人类早期应激的理想动物模型,可以用来研究早期应激诱发的某些精神疾病的发生和发展.%For rhesus monkeys, maternal separation (MS) is often used to mimic childhood adversity in humans, which can lead to brain dysfunction and, as results, behavioral abnormalities. People who suffer from psychiatric disorders due to childhood adversity usually lived a normal social life prior to the onset of the diseases. Instead, the effects of MS on rodents could be reversed by later experience. In order to identify whether the adverse effects of MS were reversible by later normal social living in rhesus monkeys, we conducted a long-term study and established an animal model for human early adversity in rhesus monkeys. The results showed that MS lead to dysfunction of HPA axis which helps manage stress and resulted abnormal behaviors in these rhesus monkeys. Furthermore, the normal social life appeared not to have obliterated the imprints of MS, suggesting that the effects of MS are long-lasting. Thus, compared to rodent models of MS, the maternal separated rhesus monkeys are a more suitable animal model to study the effects of childhood adverse experiences among people and to investigate the development of psychiatric disorders induced by exposure to childhood adversity.

  5. Characterization of a Rhesus Monkey Calicivirus Representing a New Genus of Caliciviridae▿

    OpenAIRE

    Farkas, Tibor; Sestak, Karol; Wei, Chao; Jiang, Xi

    2008-01-01

    In this study, we report the characterization of a novel calicivirus (CV), the Tulane virus (TV), which was isolated from stool samples of captive juvenile rhesus macaques (Macaca mulatta) of the Tulane National Primate Research Center. The complete genome of TV contains 6,714 nucleotides plus a poly(A) tail and is organized into three open reading frames (ORFs) that encode the nonstructural (NS) polyprotein (ORF1); the capsid protein (ORF2), with an estimated molecular mass of 57.9 kDa; and ...

  6. Directed differentiation of rhesus monkey ES cells into pancreatic cell phenotypes

    OpenAIRE

    Nauert Brian; Andrews Laura; Kuo Hung-Chih; Lester Linda B; Wolf Don P

    2004-01-01

    Abstract Embryonic stem cells (ES) can self-replicate and differentiate into all cell types including insulin-producing, beta-like cells and could, therefore, be used to treat diabetes mellitus. To date, results of stem cell differentiation into beta cells have been debated, largely due to difficulties in defining the identity of a beta cell. We have recently differentiated non-human primate (rhesus) embryonic stem (rES) cell lines into insulin producing, beta-like cells with the beta cell gr...

  7. Absorption of topically applied hydrocortisone from the eye of the rhesus monkey

    International Nuclear Information System (INIS)

    Blood samples were collected from anaesthetized monkeys during one h a) afer topical application of an eyedrop of hydrocortisone acetate suspension, b) after topical application of a drop of the vehicle alone, and c) after no application at all. Radioimmunoassay (RIA) showed a rapid and similar increase of hydrocortisone plasma levels in all 3 kinds of experiments. RIA revealed that in monkeys the anaesthetic procedure alone was sufficient to cause a considerable increase of endogenous hydrocortisone levels overshadowing any systemic absorption of topical hydrocortisone. Using tritiated hydrocortisone instead a rapid increase of systemic absorption after topical application was found. A plasma concentration of 1% of the dose was found one min after topical instillation incresing to a maximum of 6-7% at 30 min. The half time of the slow phase of elimination was about 19 h. (author)

  8. Persistence of the dark-background-contingent gaze upshift during visual fixations of rhesus monkeys.

    Science.gov (United States)

    Spivak, Oleg; Thier, Peter; Barash, Shabtai

    2014-10-15

    During visual fixations, the eyes are directed so that the image of the target (object of interest) falls on the fovea. An exception to this rule was described in macaque monkeys (though not in humans): dark background induces a gaze shift upwards, sometimes large enough to shift the target's image off the fovea. In this article we address an aspect not previously rigorously studied, the time course of the upshift. The time course is critical for determining whether the upshift is indeed an attribute of visual fixation or, alternatively, of saccades that precede the fixation. These alternatives lead to contrasting predictions regarding the time course of the upshift (durable if the upshift is an attribute of fixation, transient if caused by saccades). We studied visual fixations with dark and bright background in three monkeys. We confined ourselves to a single upshift-inducing session in each monkey so as not to study changes in the upshift caused by training. Already at their first sessions, all monkeys showed clear upshift. During the first 0.5 s after the eye reached the vicinity of the target, the upshift was on average larger, but also more variable, than later in the trial; this initial high value 1) strongly depended on target location and was maximal at locations high on the screen, and 2) appears to reflect mostly the intervals between the primary and correction saccades. Subsequently, the upshift stabilized and remained constant, well above zero, throughout the 2-s fixation interval. Thus there is a persistent background-contingent upshift genuinely of visual fixation. PMID:25057145

  9. Comparative studies on chromosome aberrations in rhesus monkeys induced by 60Co γ ray irradiation under different irradiation conditions

    International Nuclear Information System (INIS)

    Rhesus monkeys were irradiated by 60Cr γ ray exposure under different conditions, and comparative studies on their chromosome aberrations have been made. The dose rate of single acute irradiation was 223 mGy/min, the dose rate of fractionated curmulative irradiation was 223 mGy/min, and the dose of 0.25 Gy was delivered once a week, the dose rate of chronic continuous irradiation was 0.26 mGy/min for 190 min, 5 days per week. The total coumulative dose for each group was 2.0 Gy. It was found that the types of chromosome aberrations were mainly dicentric aberrations and acentric fragments in single acute irradiation, and acentric fragments in both fractionated coumulative and chronic continuous irradiation groups. The frequencies of chromosome aberrations in these groups increase linearly with increasing dose. The degree of chromosome damage in single acute irradiation group was much greater than those in the other groups, but degree and characteristics of chromosome damage between fractionated cumulative and chronic continuous irradiation groups was not significantly different. Acentric fragments in lymphocyte chromosomes ceased to increase when the cumulated dose in fractionated cumulative or chronic continuous irradiation reached to more than 1.0 Gy. The frequencies of chromosome aberrations basically decreased to control level within a year following the termination of irradiation

  10. Relationship between rate of drug uptake in brain and behavioral pharmacology of monoamine transporter inhibitors in rhesus monkeys.

    Science.gov (United States)

    Kimmel, Heather L; Negus, S Stevens; Wilcox, Kristin M; Ewing, Sarah B; Stehouwer, Jeffrey; Goodman, Mark M; Votaw, John R; Mello, Nancy K; Carroll, F Ivy; Howell, Leonard L

    2008-09-01

    Although inhibition of dopamine transporters (DAT) and the subsequent increase in dopamine clearly play a role in the effects of psychomotor stimulants, the reinforcing effectiveness of DAT inhibitors varies. Previous studies suggest that pharmacokinetic and pharmacodynamic properties of these drugs account for this variability. The present studies compared the time course and behavioral effects of five phenyltropane analogs of cocaine with high affinity for DAT and varying time courses of action in rhesus monkeys. The rate of drug uptake in putamen was measured using positron emission tomography neuroimaging. The rank order of the time to peak drug uptake was cocaineCocaine and all five analogs fully substituted for the cocaine cue in animals trained to discriminate cocaine from saline. All of the drugs were self-administered under a progressive-ratio schedule of drug self-administration and reinstated previously extinguished self-administration maintained under a second-order schedule. The time to peak drug uptake corresponded closely with the time to peak discriminative stimulus effects, and there was a trend for the time of peak drug uptake to correspond negatively with the peak number of drug infusions. Collectively, these results indicate that the rate of drug entry in brain can play an important role in the behavioral pharmacology of psychomotor stimulants. PMID:18468667

  11. Expression of Smad2 and Smad4 in rhesus monkey endometrium during the menstrual cycle and early pregnancy

    Institute of Scientific and Technical Information of China (English)

    LIN Haiyan; WANG Hongmei; LI Qinglei; WANG Juan; ZHANG Xuan; LIU Donglin; LIU Huitu; ZHU Cheng

    2003-01-01

    Expression of Smad2 and Smad4 mRNAs in the endometrium of rhesus monkey on Days 8, 20 and 28 of the normal menstrual cycle and on Days 12, 18 and 26 of early pregnancy was detected using in situ hybridization. The results showed that Smad2 and Smad4 mRNAs were mainly localized in luminal epithelium and glandular epithelium. The expression of Smad2 mRNA in glandular epithelium was sustained at moderate level on Days 8, 20 and 28 of the menstrual cycle, while the expression of Smad4 gradually increased with the menstrual cycle. Both Smad2 and Smad4 mRNAs in functionalis glandular epithelium were expressed at the highest levels on Day 12 of early pregnancy, while in basalis glandular epithelium the most abundant expression of both Smads occurred on Days 12 and 18 of pregnancy. On Day 26, both Smads mRNAs were expressed at the lowest levels either in functionalis or in basalis. The data suggest that the epithelium is the major compartment where TGF-βs/activins exert their biological effects via Smads, and that Smad4 may play a role in the maintenance of endometrial gland function during secreting period of the menstrual cycle. During lacunar stage of early pregnancy, Smad2 and Smad4 are implicated in the tissue remodeling of endometrial functionalis and basalis, and during early villous stage both Smads are functional primarily in basalis.

  12. Pharmacological inhibition of PI3K reduces adiposity and metabolic syndrome in obese mice and rhesus monkeys.

    Science.gov (United States)

    Ortega-Molina, Ana; Lopez-Guadamillas, Elena; Mattison, Julie A; Mitchell, Sarah J; Muñoz-Martin, Maribel; Iglesias, Gema; Gutierrez, Vincent M; Vaughan, Kelli L; Szarowicz, Mark D; González-García, Ismael; López, Miguel; Cebrián, David; Martinez, Sonia; Pastor, Joaquin; de Cabo, Rafael; Serrano, Manuel

    2015-04-01

    Genetic inhibition of PI3K signaling increases energy expenditure, protects from obesity and metabolic syndrome, and extends longevity. Here, we show that two pharmacological inhibitors of PI3K, CNIO-PI3Ki and GDC-0941, decrease the adiposity of obese mice without affecting their lean mass. Long-term treatment of obese mice with low doses of CNIO-PI3Ki reduces body weight until reaching a balance that is stable for months as long as the treatment continues. CNIO-PI3Ki treatment also ameliorates liver steatosis and decreases glucose serum levels. The above observations have been recapitulated in independent laboratories and using different oral formulations of CNIO-PI3Ki. Finally, daily oral treatment of obese rhesus monkeys for 3 months with low doses of CNIO-PI3Ki decreased their adiposity and lowered their serum glucose levels, in the absence of detectable toxicities. Therefore, pharmacological inhibition of PI3K is an effective and safe anti-obesity intervention that could reverse the negative effects of metabolic syndrome in humans. PMID:25817535

  13. Immunoglobulins and complement in the skin of Rhesus monkeys immunized with X-irradiated cercariae of Schistosoma japonicum

    Energy Technology Data Exchange (ETDEWEB)

    Li-Hsue, S.Y.; Hsue, H.F.; Hanson, H.O.

    1981-01-01

    Skin sections of Rhesus monkeys immunized with X-irradiated Schistosoma japonicum cercariae were stained by an unlabeled antibody enzyme method for the detection of IgG, IgM, IgA, IgE, and C3. While all of them could be found in the skin lesions, their distribution patterns varied with time and reactions. In whealing reaginic reactions, IgE appeared prominent, having an affinity to the mast cells. In Arthus-like reactions, IgG was predominant. IgG complexes were found on the schistosomula, on the walls of blood vessels, and in granulocytes near the schistosomula. In the late stage of Arthus-like reactions and in delayed hypersensitive reactions, IgA was predominant in granulocytes, mononuclear cells, and macrophages. Characteristics of each immunoglobulin pattern seemed to reflect its function in the effector mechanism. It may be speculated that these immunoglobulins and C3, together with effector cells, synergistically and sequentially destroy schistosomula in the skin.

  14. Immunoglobulins and complement in the skin of Rhesus monkeys immunized with X-irradiated cercariae of Schistosoma japonicum

    International Nuclear Information System (INIS)

    Skin sections of Rhesus monkeys immunized with X-irradiated Schistosoma japonicum cercariae were stained by an unlabeled antibody enzyme method for the detection of IgG, IgM, IgA, IgE, and C3. While all of them could be found in the skin lesions, their distribution patterns varied with time and reactions. In whealing reaginic reactions, IgE appeared prominent, having an affinity to the mast cells. In Arthus-like reactions, IgG was predominant. IgG complexes were found on the schistosomula, on the walls of blood vessels, and in granulocytes near the schistosomula. In the late stage of Arthus-like reactions and in delayed hypersensitive reactions, IgA was predominant in granulocytes, mononuclear cells, and macrophages. Characteristics of each immunoglobulin pattern seemed to reflect its function in the effector mechanism. It may be speculated that these immunoglobulins and C3, together with effector cells, synergistically and sequentially destroy schistosomula in the skin. (orig.)

  15. Cytoarchitecture and cortical connections of the anterior insula and adjacent frontal motor fields in the rhesus monkey.

    Science.gov (United States)

    Morecraft, R J; Stilwell-Morecraft, K S; Ge, J; Cipolloni, P B; Pandya, D N

    2015-10-01

    The cytoarchitecture and cortical connections of the ventral motor region are investigated using Nissl, and NeuN staining methods and the fluorescent retrograde tract tracing technique in the rhesus monkey. On the basis of gradual laminar differentiation, it is shown that the ventral motor region stems from the ventral proisocortical area (anterior insula and dorsal Sylvian opercular region). The cytoarchitecture of the ventral motor region is shown to progress in three lines, as we have recently shown for the dorsal motor region. Namely, root (anterior insular and dorsal Sylvian opercular area ProM), belt (ventral premotor cortex) and core (precentral motor cortex) lines. This stepwise architectonic organization is supported by the overall patterns of corticocortical connections. Areas in each line are sequentially interconnected (intralineal connections) and all lines are interconnected (interlinear connections). Moreover, root areas, as well as some of the belt areas of the ventral and dorsal trend are interconnected. The ventral motor region is also connected with the ventral somatosensory areas in a topographic manner. The root and belt areas of ventral motor region are connected with paralimbic, multimodal and prefrontal (outer belt) areas. In contrast, the core area has a comparatively more restricted pattern of corticocortical connections. This architectonic and connectional organization is consistent in part, with the functional organization of the ventral motor region as reported in behavioral and neuroimaging studies which include the mediation of facial expression and emotion, communication, phonic articulation, and language in human. PMID:26496798

  16. Application of three-dimensional culture systems to study mammalian spermatogenesis, with an emphasis on the rhesus monkey (Macaca mulatta).

    Science.gov (United States)

    Huleihel, Mahmoud; Nourashrafeddin, Seyedmehdi; Plant, Tony M

    2015-01-01

    In vitro culture of spermatogonial stem cells (SSCs) has generally been performed using two-dimensional (2D) culture systems; however, such cultures have not led to the development of complete spermatogenesis. It seems that 2D systems do not replicate optimal conditions of the seminiferous tubules (including those generated by the SSC niche) and necessary for spermatogenesis. Recently, one of our laboratories has been able to induce proliferation and differentiation of mouse testicular germ cells to meiotic and postmeiotic stages including generation of sperm in a 3D soft agar culture system (SACS) and a 3D methylcellulose culture system (MCS). It was suggested that SACS and MCS form a special 3D microenvironment that mimics germ cell niche formation in the seminiferous tubules, and thus permits mouse spermatogenesis in vitro. In this review, we (1) provide a brief overview of the differences in spermatogenesis in rodents and primates, (2) summarize data related to attempts to generate sperm in vitro, (3) report for the first time formation of colonies/clusters of cells and differentiation of meiotic (expression of CREM-1) and postmeiotic (expression of acrosin) germ cells from undifferentiated spermatogonia isolated from the testis of prepubertal rhesus monkeys and cultured in SACS and MCS, and (4) indicate research needed to optimize 3D systems for in vitro primate spermatogenesis and for possible future application to man. PMID:26067870

  17. Funduscopic alterations in the rhesus monkey induced by exposure to heavy ions /0+8/ 250 MeV/nucleon

    Science.gov (United States)

    Beckman, F. N.; Bonney, C. H.; Hunter, D. M.

    1974-01-01

    A heavy-ion, high-energy beam has been extracted from the Lawrence Radiation Laboratory Bevatron, making controlled exposure of biological systems feasible, and a series of experiments have been undertaken to determine the possible deleterious effects of such irradiation upon the primate retina. The left eyes of 54 rhesus monkeys have been exposed to accelerated 0+8 (250 MeV/nucleon). Beam flux ranged from 1.3 x 10 to the 7th particles/ sq cm (171 rads) to 5.9 x 10 to the 8th particles/sq cm (7740 rads). Fundus photography was performed immediately prior to and immediately following exposure, at 24 to 48 hours postexposure and at 1, 2, and 5 weeks postexposure. Punctate hemorrhages of the retina were visible at 1.3 x 10 to the 7th particles/sq cm (171 rads), the lowest exposure level utilized in this study. Acute radiation retinopathy, consisting of geographic retinal hemorrhage and ischemic necrosis of the retina, was not seen until total flux reached 7.7 x 10 to the 7th particles/sq cm (1000 rads).

  18. Application of three-dimensional culture systems to study mammalian spermatogenesis, with an emphasis on the rhesus monkey (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Mahmoud Huleihel

    2015-01-01

    Full Text Available In vitro culture of spermatogonial stem cells (SSCs has generally been performed using two-dimensional (2D culture systems; however, such cultures have not led to the development of complete spermatogenesis. It seems that 2D systems do not replicate optimal conditions of the seminiferous tubules (including those generated by the SSC niche and necessary for spermatogenesis. Recently, one of our laboratories has been able to induce proliferation and differentiation of mouse testicular germ cells to meiotic and postmeiotic stages including generation of sperm in a 3D soft agar culture system (SACS and a 3D methylcellulose culture system (MCS. It was suggested that SACS and MCS form a special 3D microenvironment that mimics germ cell niche formation in the seminiferous tubules, and thus permits mouse spermatogenesis in vitro. In this review, we (1 provide a brief overview of the differences in spermatogenesis in rodents and primates, (2 summarize data related to attempts to generate sperm in vitro, (3 report for the first time formation of colonies/clusters of cells and differentiation of meiotic (expression of CREM-1 and postmeiotic (expression of acrosin germ cells from undifferentiated spermatogonia isolated from the testis of prepubertal rhesus monkeys and cultured in SACS and MCS, and (4 indicate research needed to optimize 3D systems for in vitroprimate spermatogenesis and for possible future application to man.

  19. Effects of mixed neutron-γ total-body irradiation on physical activity performance of rhesus monkeys

    International Nuclear Information System (INIS)

    Behavioral incapacitation for a physical activity task and its relationship to emesis and survival time following exposure to ionizing radiation were evaluated in 39 male rhesus monkeys (Macaca mulatta). Subjects were trained to perform a shock avoidance activity task for 6 hr on a 10-min work/5-min rest schedule in a nonmotorized physical activity wheel. Following stabilization of performance, each subject received a single, pulsed dose of mixed neutron-γ, whole-body radiation (n/γ = 3.0) ranging between 1274 and 4862 rad. Performance testing was started 45 sec after exposure. A dose-response function for early transient incapacitation (ETI) during the first 2 hr after irradiation was fitted, and the median effective dose (ED50) was calculated to be 1982 rad. Analysis done on the relationship of dose to ETI, emesis, and survival time found (a) a significant relationship between the radiation dose and the number and duration of ETIs; (b) no correlation between emesis and dose, survival time, or ETI; (c) no relation between survival time and ETI at any dose; and (d) no significant difference in survival time for dose groups between 1766 +/- 9 (SEM) and 2308 +/- 23 rad

  20. Species diversity and relative abundance of lactic acid bacteria in the milk of rhesus monkeys (Macaca mulatta)

    Science.gov (United States)

    Jin, L.; Hinde, K.; Tao, L.

    2013-01-01

    Background Mother’s milk is a source of bacteria that influences the development of the infant commensal gut microbiota. To date, the species diversity and relative abundance of lactic acid bacteria in the milk of non-human primates have not been described. Methods Milk samples were aseptically obtained from 54 female rhesus monkeys (Macaca mulatta) at peak lactation. Following GM17 and MRS agar plating, single bacterial colonies were isolated based on difference in morphotypes, then grouped based on whole-cell protein profiles on SDS–PAGE. Bacterial DNA was isolated and the sequence the 16S rRNA gene was analyzed. Results A total of 106 strains of 19 distinct bacterial species, belonging to five genera, Bacillus, Enterococcus, Lactobacillus, Pediococcus, and Streptococcus, were identified. Conclusions Maternal gut and oral commensal bacteria may be translocated to the mammary gland during lactation and present in milk. This pathway can be an important source of commensal bacteria to the infant gut and oral cavity. PMID:20946146

  1. Experimental Chagas' disease in rhesus monkeys. I. Clinical, parasitological, hematological and anatomo-pathological studies in the acute and indeterminate phase of the disease.

    Science.gov (United States)

    Bonecini-Almeida, M da G; Galvão-Castro, B; Pessoa, M H; Pirmez, C; Laranja, F

    1990-01-01

    Rhesus monkeys (Macaca mulatta) were infected subcutaneously with 1.0 x 10(4) to 1.5 x 10(4) metacyclic trypomastigotes of Trypanosoma cruzi (Colombian strain). Parasitological and immunological parameters were evaluated in these animals for periods of 1 month to over 3 years. A chagoma was observed between the 3rd and the 13th day after infection (a.i.) and patent parasitaemia between the 13th and 59th day a.i.. Thereafter, parasites were demonstrated only by haemoculture and/or xenodiagnosis. Circulating specific IgM and IgG antibodies were observed as early as in the 2nd week a.i. IgG levels persisted until the end of the experiment, but IgM antibodies were detectable nine months a.i. Haematological alterations comprised leucocytosis and lymphocytosis. Electrocardiographic alterations were minor and transient, similar to those observed in non-lethal human acute Chagas' myocarditis. Myocarditis and myositis, characterized by multiple foci of lympho-histiocyte inflammatory infiltrate, were present in monkeys sacrificed on the 41st, 70th and 76th day but not in the animal sacrificed 3 years and 3 months a. i.. The results suggest that Chagas' disease in rhesus monkeys reproduces the acute and indeterminate phases of human Chagas' disease. PMID:2128360

  2. Experimental chagas' disease in rhesus monkeys. I. Clinical parasitological, hematological and anatomo-pathological studies in the acute and indeterminate phase of the disease

    Directory of Open Access Journals (Sweden)

    Maria da Glória Bonecine-Almeida

    1990-06-01

    Full Text Available Rhesus monkeys (macaca mulatta were infected subcutaneously with 1.0 x 10**4 to 1.5 x 10**4 metacyclic trypomastigotes of Trypanosoma cruzi (Colombian strain. Parasitological and immunological parameters were evaluated in these animals for periods of 1 month to over 3 years. a chagona was observed between the 3 rd and the 13th day after infection (a.i and patent parasitaemia between the 13th and 59th day a.i.. Thereafter, parasites were demonstrated only by haemoculture and/or xenodiagnosis. Circulating specifc IgM and IgC antibodies were observed as early as in the 2nd week a. i. IgG levels persisted until the end of the expriment, but IgM antibodies were detectable nine months a. i. Haematological alterations comprised leucocytosis and lymphocytosis. Eletrocardiographic alterations were minor and transient, similar to those observe in non-lethal human acute Chagas' myocarditis. Myocarditis and myositis, characterized by multiple foci of lympho-histiocyte inflammatory infiltrate, were present in monkeys sacrificed on the 41 th, 70th and 76 th day but not in the animal sacrificed 3 years and 3 months a. i.. The results suggest that Chagas' disease in rhesus monkeys reproduces the acute and indeterminate phases of human Chagas' disease.

  3. Combined Treatment with Morphine and Δ9-Tetrahydrocannabinol in Rhesus Monkeys: Antinociceptive Tolerance and Withdrawal.

    Science.gov (United States)

    Gerak, L R; France, C P

    2016-05-01

    Opioid receptor agonists are effective for treating pain; however, tolerance and dependence can develop with repeated use. Combining opioids with cannabinoids can enhance their analgesic potency, although it is less clear whether combined treatment alters opioid tolerance and dependence. In this study, four monkeys received 3.2 mg/kg morphine alone or in combination with 1 mg/kg Δ(9)-tetrahydrocannabinol (THC) twice daily; the antinociceptive effects (warm water tail withdrawal) of morphine, the cannabinoid receptor agonists WIN 55,212 [(R)-(1)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate] and CP 55,940 (2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-5-(2-methyloctan-2-yl)phenol), and the κ opioid receptor agonist U-50,488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzenacetamide methanesulfonate) were examined before, during, and after treatment. To determine whether concurrent THC treatment altered morphine dependence, behavioral signs indicative of withdrawal were monitored when treatment was discontinued. Before treatment, each drug increased tail withdrawal latency to 20 seconds (maximum possible effect). During treatment, latencies did not reach 20 seconds for morphine or the cannabinoids up to doses 3- to 10-fold larger than those that were fully effective before treatment. Rightward and downward shifts in antinociceptive dose-effect curves were greater for monkeys receiving the morphine/THC combination than monkeys receiving morphine alone. When treatment was discontinued, heart rate and directly observable withdrawal signs increased, although they were generally similar in monkeys that received morphine alone or with THC. These results demonstrated that antinociceptive tolerance was greater during treatment with the combination, and although treatment conditions were sufficient to result in the development of dependence on morphine, withdrawal was not

  4. The cannabinoid agonist HU-210: pseudo-irreversible discriminative stimulus effects in rhesus monkeys

    OpenAIRE

    Hruba, Lenka; McMahon, Lance R.

    2014-01-01

    Synthetic cannabinoid abuse and case reports of adverse effects have raised concerns about the pharmacologic mechanisms underlying in vivo effects. Here, a synthetic cannabinoid identified in abused products (HU-210) was compared to the effects of Δ9-THC and two other synthetic cannabinoid agonists used extensively in pre-clinical studies (CP 55,940 and WIN 55,212-2). One group of monkeys discriminated Δ9-THC (0.1 mg/kg i.v.); a separate group received chronic Δ9-THC (1 mg/kg/12 h s.c.) and d...

  5. Neurotoxic lesions of perirhinal cortex impair visual recognition memory in rhesus monkeys.

    Science.gov (United States)

    Málková, L; Bachevalier, J; Mishkin, M; Saunders, R C

    2001-07-01

    Recent excitotoxic lesion studies in monkeys have shown that the recognition memory deficits originally attributed to amygdalo-hippocampal damage were due in whole or in part to the accompanying damage to surrounding tissue, including fibers of passage. Here we show that the same conclusion does not apply to the visual recognition impairment produced by aspiration lesions of perirhinal cortex inasmuch as equally severe impairment was found after excitotoxic lesions of this cortex. The finding demonstrates that damage limited to perirhinal neurons is sufficient to impair visual memory and that damage to fibers of passage neither caused nor exacerbated the effect described initially. PMID:11435922

  6. Long-term effects of simulated sonic booms on hearing in rhesus monkeys

    Science.gov (United States)

    Reinis, S.; Weiss, D. S.; Featherstone, J. W.; Tsaros, C.

    1987-03-01

    Two monkeys of the species Macaca mulatta were exposed at 1 min intervals to five simulated sonic booms lasting 200 ms at 200 Pa overpressure with a 10 ms rise time. Another group of five monkeys of the same species were exposed to 100 booms. Their hearing thresholds were tested 24 hours, two weeks, one month, two months, four months and six months later. In one animal exposed to five booms, changes of the hearing thresholds were observed 24 hours following the exposure, but not later. All five animals exposed to 100 sonic booms had threshold shifts in the high-frequency range 24 hours following the exposure. Of the three animals followed for the full period of six months, one recovered completely. In the two others, threshold shifts were still observed in the high frequency range. Histological examination revealed destruction of the organ of Corti in the basal turn of the cochlea. These data indicate that there is individual variability in the extent of the damage to the inner ear by the sonic boom (and, perhaps, by other types of impulsive noise). These data also indicate that there is a possibility of similar damage to human inner ears exposed either to sonic booms or to other types of impulsive noise, and that it may go undetected for a long time because the high-frequency hearing defect, over 8 kHz, may be overlooked when routine audiometric methods are used.

  7. Sleeve bridging of the rhesus monkey ulnar nerve with muscular branches of the pronator teres:multiple ampliifcation of axonal regeneration

    Institute of Scientific and Technical Information of China (English)

    Yu-hui Kou; Pei-xun Zhang; Yan-hua Wang; Bo Chen; Na Han; Feng Xue; Hong-bo Zhang; Xiao-feng Yin; Bao-guo Jiang

    2015-01-01

    Multiple-bud regeneration,i.e., multiple amplification, has been shown to exist in peripheral nerve regeneration. Multiple buds grow towards the distal nerve stump during proximal nerve ifber regeneration. Our previous studies have veriifed the limit and validity of multiple ampli-ifcation of peripheral nerve regeneration using small gap sleeve bridging of small donor nerves to repair large receptor nerves in rodents. The present study sought to observe multiple ampli-ifcation of myelinated nerve ifber regeneration in the primate peripheral nerve. Rhesus monkey models of distal ulnar nerve defects were established and repaired using muscular branches of the right forearm pronator teres. Proximal muscular branches of the pronator teres were su-tured into the distal ulnar nerve using the small gap sleeve bridging method. At 6 months after suture, two-ifnger lfexion and mild wrist lfexion were restored in the ulnar-sided injured limbs of rhesus monkey. Neurophysiological examination showed that motor nerve conduction veloc-ity reached 22.63 ± 6.34 m/s on the affected side of rhesus monkey. Osmium tetroxide staining demonstrated that the number of myelinated nerve fibers was 1,657 ± 652 in the branches of pronator teres of donor, and 2,661 ± 843 in the repaired ulnar nerve. The rate of multiple ampliifcation of regenerating myelinated nerve ifbers was 1.61. These data showed that when muscular branches of the pronator teres were used to repair ulnar nerve in primates, effective regeneration was observed in regenerating nerve ifbers, and functions of the injured ulnar nerve were restored to a certain extent. Moreover, multiple ampliifcation was subsequently detected in ulnar nerve axons.

  8. Human Immunodeficiency Virus Type 1 Envelope Epitope-Specific CD4+ T Lymphocytes in Simian/Human Immunodeficiency Virus-Infected and Vaccinated Rhesus Monkeys Detected Using a Peptide-Major Histocompatibility Complex Class II Tetramer

    OpenAIRE

    Kuroda, Marcelo J.; Schmitz, Jörn E.; Lekutis, Christine; Nickerson, Christine E.; Lifton, Michelle A.; Franchini, Genoveffa; Harouse, Janet M.; Cheng-Mayer, Cecilia; Letvin, Norman L.

    2000-01-01

    A tetrameric recombinant major histocompatibility complex (MHC) class II-peptide complex was used to quantitate human immunodeficiency virus type 1 (HIV-1) envelope (Env)-specific CD4+ T cells in vaccinated and in simian/human immunodeficiency virus (SHIV)-infected rhesus monkeys. A rhesus monkey MHC class II DR molecule, Mamu-DR*W201, and an HIV-1 Env peptide (p46) were employed to construct this tetrameric complex. A p46-specific proliferative response was seen in sorted, tetramer-binding, ...

  9. Analysis of Gag-specific Cytotoxic T Lymphocytes in Simian Immunodeficiency Virus–infected Rhesus Monkeys by Cell Staining with a Tetrameric Major Histocompatibility Complex Class I–Peptide Complex

    OpenAIRE

    Kuroda, Marcelo J.; Schmitz, Jörn E.; Barouch, Dan H.; Craiu, Abie; Allen, Todd M.; Sette, Alessandro; Watkins, David I.; Forman, Meryl A.; Letvin, Norman L.

    1998-01-01

    A tetrameric recombinant major histocompatibility complex (MHC) class I–peptide complex was used as a staining reagent in flow cytometric analyses to quantitate and define the phenotype of Gag-specific cytotoxic T lymphocytes (CTLs) in the peripheral blood of simian immunodeficiency virus macaque (SIVmac)-infected rhesus monkeys. The heavy chain of the rhesus monkey MHC class I molecule Mamu-A*01 and β2-microglobulin were refolded in the presence of an SIVmac Gag synthetic peptide (p11C, C–M)...

  10. Elicitation of High-Frequency Cytotoxic T-Lymphocyte Responses against both Dominant and Subdominant Simian-Human Immunodeficiency Virus Epitopes by DNA Vaccination of Rhesus Monkeys

    OpenAIRE

    Barouch, Dan H.; Craiu, Abie; Santra, Sampa; Egan, Michael A.; Schmitz, Jörn E.; Kuroda, Marcelo J.; Fu, Tong-Ming; Nam, Jae-Hwan; Wyatt, Linda S.; Lifton, Michelle A.; Krivulka, Georgia R.; Nickerson, Christine E.; Lord, Carol I.; Moss, Bernard; Lewis, Mark G.

    2001-01-01

    Increasing evidence suggests that the generation of cytotoxic T-lymphocyte (CTL) responses specific for a diversity of viral epitopes will be needed for an effective human immunodeficiency virus type 1 (HIV-1) vaccine. Here, we determine the frequencies of CTL responses specific for the simian immunodeficiency virus Gag p11C and HIV-1 Env p41A epitopes in simian-human immunodeficiency virus (SHIV)-infected and vaccinated rhesus monkeys. The p11C-specific CTL response was high frequency and do...

  11. Simian Immunodeficiency Virus (SIV) gag DNA-Vaccinated Rhesus Monkeys Develop Secondary Cytotoxic T-Lymphocyte Responses and Control Viral Replication after Pathogenic SIV Infection

    OpenAIRE

    Egan, Michael A.; Charini, William A.; Kuroda, Marcelo J.; Schmitz, Jörn E.; Racz, Paul; Tenner-Racz, Klara; Manson, Kelledy; Wyand, Michael; Lifton, Michelle A.; Nickerson, Christie E.; Fu, Tongming; Shiver, John W.; Letvin, Norman L.

    2000-01-01

    The potential contribution of a plasmid DNA construct to vaccine-elicited protective immunity was explored in the simian immunodeficiency virus (SIV)/macaque model of AIDS. Making use of soluble major histocompatibility class I/peptide tetramers and peptide-specific killing assays to monitor CD8+ T-lymphocyte responses to a dominant SIV Gag epitope in genetically selected rhesus monkeys, a codon-optimized SIV gag DNA vaccine construct was shown to elicit a high-frequency SIV-specific cytotoxi...

  12. Experimental chagas' disease in rhesus monkeys. I. Clinical parasitological, hematological and anatomo-pathological studies in the acute and indeterminate phase of the disease

    OpenAIRE

    Maria da Glória Bonecine-Almeida; Bernardo Galvão-Castro; Maria Heleosina Ribeiro Pessoa; Claude Piramez; Francisco Laranja

    1990-01-01

    Rhesus monkeys (macaca mulatta) were infected subcutaneously with 1.0 x 10**4 to 1.5 x 10**4 metacyclic trypomastigotes of Trypanosoma cruzi (Colombian strain). Parasitological and immunological parameters were evaluated in these animals for periods of 1 month to over 3 years. a chagona was observed between the 3 rd and the 13th day after infection (a.i) and patent parasitaemia between the 13th and 59th day a.i.. Thereafter, parasites were demonstrated only by haemoculture and/or xenodiagnosi...

  13. Estradiol effects on behavior and serum oxytocin are modified by social status and polymorphisms in the serotonin transporter gene in female rhesus monkeys

    OpenAIRE

    Michopoulos, Vasiliki; Checchi, Marta; Sharpe, Desiree; Wilson, Mark E.

    2011-01-01

    Despite the well-documented relation between estradiol (E2) and behavior, exposure to stressors may modify sensitivity to E2. The effects of E2 on behavior are, in part, likely related to their modulation of the serotonin (5HT) and oxytocin systems. The short allele (s-variant) polymorphism found in the promoter region of the SLC6A4 gene that encodes the 5HT transporter (5HTT) modulates responsivity to stressors. The current study used ovariectomized adult female rhesus monkeys to evaluate ho...

  14. Combined expression of CTGF and tissue inhibitor of metalloprotease-1 promotes synthesis of proteoglycan and collagen type Ⅱ in rhesus monkey lumbar intervertebral disc cells in vitro

    Institute of Scientific and Technical Information of China (English)

    LIU Yong; KONG Jie; CHEN Bo-hua; HU You-gu

    2010-01-01

    Background Low back pain has emerged as a widespread disease often caused by intervertebral disc degeneration.This study aimed to establish an in vitro cell culture model of rhesus monkey lumbar intervertebral discs and to investigate the effect of combined connective tissue growth factor (CTGF) and tissue inhibitor of metalloprotease-1(TIMP-1) expression mediated by adeno-associated virus (AAV) on collagen type Ⅱ and proteoglycan levels.The purpose of these investigations was to explore potential methods for relieving the degeneration of lumbar intervertebral disc cells.Methods Rhesus monkey lumbar intervertebral disc nucleus pulposus cells (NPCs) were isolated by enzyme digestion,cultured, and transduced with rAAV2-CTGF-IRES-TIMP-1, rAAV2-CTGF, or rAAV2-TIMP-1 at a multiplicity of infection (MOl) of 106.The expression of collagen type Ⅱ and proteoglycan was measured using RT-PCR and Western blotting.The synthetic rate of proteoglycan was measured using 35S incorporation.Results Rhesus monkey lumbar intervertebral disc NPCs were transduced with rAAV2-CTGF-IRES-TIMP-1,rAAV2-CTGF, and rAAV2-TIMP-1 and the transduced genes were expressed and detected.Compared to the control,CTGF promoted the synthesis of collagen type Ⅱ and proteoglycan.TIMP-1 showed an enhancing effect on the expression of proteoglycan but no effect on collagen type Ⅱ.Expression of both genes in rhesus monkey lumbar intervertebral disc NPCs significantly enhances the synthesis of proteoglycan and collagen type Ⅱ.Conclusions Single gene transduction of CTGF or TIMP-1 can enhanced synthesis of proteoglycan.CTGF expression can also enhance collagen type Ⅱ protein synthesis.Combined transduction of both CTGF and TIMP1 can significantly promote the expression of proteoglycan and collagen type Ⅱ to levels greater than transduction of a single gene alone.Our study provides a good basis for multi-gene therapy to treat lumbar intervertebral disc degeneration.

  15. Comparison of the effects of 50 MeV/sub d → Be/ neutron and cobalt-60 irradiation of the kidneys of Rhesus monkeys

    International Nuclear Information System (INIS)

    Twenty rhesus monkeys had one kidney irradiated (after undergoing unilateral nephrectomies) with one of four doses: 960 or 1080 rads of 50 MeV/sub d→Be/ neutrons, or 2350 or 2700 rads of 60Co. Whereas animals treated with the lower dose of neutrons or 60Co are alive with relatively normal renal function, those treated with the higher dose of neutrons died of radiation nephritis. Animals treated with the higher dose of 60Co developed radiation nephritis but survived. The physiological and histopathological changes of radiation nephritis secondary to neutron irradiation are not qualitatively different from those reported for radiation nephritis secondary to photon irradiation

  16. Recombinant, Live-Attenuated Tetravalent Dengue Virus Vaccine Formulations Induce a Balanced, Broad, and Protective Neutralizing Antibody Response against Each of the Four Serotypes in Rhesus Monkeys

    OpenAIRE

    Blaney, Joseph E.; Matro, Jennifer M.; Murphy, Brian R.; Whitehead, Stephen S

    2005-01-01

    Three tetravalent vaccine (TV) formulations of previously described monovalent dengue (DEN) virus vaccine candidates were compared to a tetravalent formulation of wild-type DEN viruses (T-wt) for replication in SCID mice transplanted with human liver cells (SCID-HuH-7) or for replication and immunogenicity in rhesus monkeys. TV-1 consists of recombinant DEN1, -2, -3, and -4, each with a 30-nucleotide deletion in the 3′ untranslated region (Δ30). TV-2 consists of rDEN1Δ30, rDEN4Δ30, and two an...

  17. Extreme Dependence of gH and gL Expression on ORF57 and Association with Highly Unusual Codon Usage in Rhesus Monkey Rhadinovirus▿

    OpenAIRE

    John P Bilello; Morgan, Jennifer S.; Desrosiers, Ronald C.

    2008-01-01

    Standard vectors for high-level expression elicited undetectable levels of the gH and gL glycoproteins of rhesus monkey rhadinovirus (RRV) following transient-transfection assays under a variety of conditions. These same vectors and conditions yielded high levels of RRV gB expression. Unlike other genes of RRV, both the gH and gL genes were noted to have a highly aberrant, suboptimal codon usage. High levels of RRV gH and gL expression were achieved by two alternative means: codon optimizatio...

  18. Spaceflight and growth effects on muscle fibers in the rhesus monkey

    Science.gov (United States)

    Bodine-Fowler, Sue C.; Roy, Roland R.; Rudolph, William; Haque, Naz; Kozlovskaia, Inessa B.; Edgerton, V. R.

    1992-01-01

    The effect of a 14-day spaceflight onboard Cosmos 2044 on selected morphological and metabolic properties of single muscle fibers was investigated in a nonhuman primate, Macaca mulatta. It is concluded that the 14-day spaceflight had little impact on fiber size in the soleus (S) and medial gastrocnemius (MG) muscles, whereas it appeared to be a slight decrease in sized in the tibialis anterior (TA). The mean fiber size in the postflight biopsies increased relative to preflight values. The mean fiber succinate dehydrogenase activity was found to decrease in the MG, whereas there was no apparent effect of spaceflight on the s and ta muscles. The differences in response of the S, MG, and TA to spaceflight in monkeys vs rats may be related to a species responsiveness to spaceflight, the manner in which the animals were restrained, and/or the possibility that the ankle musculature was able to function against a load while in space.

  19. No strings attached: Physiological Monitoring of Rhesus Monkeys (Macaca mulatta with Thermal Imaging.

    Directory of Open Access Journals (Sweden)

    Stephanos Ioannou

    2015-06-01

    Full Text Available Methodological challenges make physiological affective observations very restrictive as in many cases they take place in a laboratory setting rather than the animals’ natural habitat. In the current study using Infrared Thermal Imaging we examine the physiological thermal imprints of 5 macaques. The monkeys were exposed in 3 different experimental scenarios. Playing with a toy, food teasing as well as feeding. It was observed that during teasing the temperature of the region surrounding the eyes was higher than play as a result of rapid saccades directed at the food. Compared to play and teasing, a lower temperature accompanied feeding on the upper lip, nose and orbital region suggesting elevated levels of distress. These findings prove that thermal imaging is a reliable method of physiological monitoring the subject at a distance while preserving a semi-experimental setting.

  20. Sympathoadrenal responses to cold and ketamine anesthesia in the rhesus monkey

    Science.gov (United States)

    Kolka, M. A.; Elizondo, R. S.; Weinberg, R. P.

    1983-01-01

    The effect of cold exposure on the sympathoadrenal system is investigated in eight adult rhesus monekys with and without ketamine anesthesia. It is found that a 3 hr cold exposure (12 c) was associated with a 175 percent increase above control levels of norepinephrine (NE) and a 100 percent increase in epinephrine (E). Also observed were decreases in the core temperature, mean skin temperature, and mean body temperature. No change in the plasma levels of NE and E from the control values was found during continuous infusion of ketamine; while the core temperature, mean skin temperature, and mean body temperature all showed greater declines with the addition of ketamine infusion to the cold exposure. Water exposure (28 C) under ketamine anesthesia resulted in a reduction of the core temperature to 33 C within 1 hr. Plasma levels of NE and E were found to be unchanged from control values at core temperatures of 35 and 33 C. It is concluded that the administration of ketamine abolishes both the thermoregulatory response and the catecholamine response to acute cold exposure.

  1. Blood to brain iron uptake in one Rhesus monkey using [Fe-52]-citrate and positron emission tomography (PET): influence of haloperidol

    International Nuclear Information System (INIS)

    Iron is highly concentrated in the basal ganglia of the brain. The involvement of cerebral iron and its handling systems in neurodegenerative brain diseases like Parkinson's disease and tardive dyskinesia is currently under close investigation. There is evidence from animal studies that neuroleptics can increase iron uptake into brain. This effect appeared to be due to alteration of blood-brain barrier transport by the neuroleptics, particularly chlorpromazine and haloperidol, but not clozapine. We have investigated one Rhesus monkey using positron emission tomography (PET) and [Fe-52]-citrate before and during haloperidol administration. After drug withdrawal during a period of 1.5 year the investigation procedure was repeated. The results show that in the investigated monkey haloperidol induces a reversible marked increase of iron transport across the blood brain barrier concomitant with a large increase in elimination rate of the tracer from the blood. (author)

  2. Blood to brain iron uptake in one rhesus monkey using [Fe-52]-citrate and positron emission tomography (PET): influence of haloperidol.

    Science.gov (United States)

    Leenders, K L; Antonini, A; Schwarzbach, R; Smith-Jones, P; Reist, H; Ben-Shachar, D; Youdim, M; Henn, V

    1994-01-01

    Iron is highly concentrated in the basal ganglia of the brain. The involvement of cerebral iron and its handling systems in neurodegenerative brain diseases like Parkinson's disease and tardive dyskinesia is currently under close investigation. There is evidence from animal studies that neuroleptics can increase iron uptake into brain. This effect appeared to be due to alteration of blood-brain barrier transport by the neuroleptics, particularly chlorpromazine and haloperidol, but not clozapine. We have investigated one Rhesus monkey using positron emission tomography (PET) and [Fe-52]-citrate before and during haloperidol administration. After drug withdrawal during a period of 1.5 year the investigation procedure was repeated. The results show that in the investigated monkey haloperidol induces a reversible marked increase of iron transport across the blood brain barrier concomitant with a large increase in elimination rate of the tracer from the blood. PMID:7884394

  3. Effects of Environmental Manipulations and Treatment with Bupropion and Risperidone on Choice between Methamphetamine and Food in Rhesus Monkeys.

    Science.gov (United States)

    Banks, Matthew L; Blough, Bruce E

    2015-08-01

    Preclinical and human laboratory choice procedures have been invaluable in improving our knowledge of the neurobiological mechanisms of drug reinforcement and in the drug development process for candidate medications to treat drug addiction. However, little is known about the neuropharmacological mechanisms of methamphetamine vs food choice. The aims of this study were to develop a methamphetamine vs food choice procedure and determine treatment effects with two clinically relevant compounds: the monoamine uptake inhibitor bupropion and the dopamine antagonist risperidone. Rhesus monkeys (n=6) responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, FR10 schedule) during 7-day bupropion (0.32-1.8 mg/kg/h) and risperidone (0.001-0.0056 mg/kg/h) treatment periods. For comparison, effects of removing food pellets or methamphetamine injections and FR response requirement manipulations were also examined. Under saline treatment conditions, food was preferred over no methamphetamine or small unit methamphetamine doses (0.01-0.032 mg/kg/injection). Larger methamphetamine doses resulted in greater methamphetamine preference and 0.32 mg/kg/injection methamphetamine maintained near exclusive preference. Removing food availability increased methamphetamine choice, whereas removing methamphetamine availability decreased methamphetamine choice. Methamphetamine choice was not significantly altered when the FR response requirements for food and drug were the same (FR100:FR100 or FR10:FR10). Risperidone treatment increased methamphetamine choice, whereas bupropion treatment did not alter methamphetamine choice up to doses that decreased rates of operant behavior. Overall, these negative results with bupropion and risperidone are concordant with previous human laboratory and clinical trials and support the potential validity of this preclinical methamphetamine vs food

  4. Head movements evoked in alert rhesus monkey by vestibular prosthesis stimulation: implications for postural and gaze stabilization.

    Directory of Open Access Journals (Sweden)

    Diana E Mitchell

    Full Text Available The vestibular system detects motion of the head in space and in turn generates reflexes that are vital for our daily activities. The eye movements produced by the vestibulo-ocular reflex (VOR play an essential role in stabilizing the visual axis (gaze, while vestibulo-spinal reflexes ensure the maintenance of head and body posture. The neuronal pathways from the vestibular periphery to the cervical spinal cord potentially serve a dual role, since they function to stabilize the head relative to inertial space and could thus contribute to gaze (eye-in-head + head-in-space and posture stabilization. To date, however, the functional significance of vestibular-neck pathways in alert primates remains a matter of debate. Here we used a vestibular prosthesis to 1 quantify vestibularly-driven head movements in primates, and 2 assess whether these evoked head movements make a significant contribution to gaze as well as postural stabilization. We stimulated electrodes implanted in the horizontal semicircular canal of alert rhesus monkeys, and measured the head and eye movements evoked during a 100 ms time period for which the contribution of longer latency voluntary inputs to the neck would be minimal. Our results show that prosthetic stimulation evoked significant head movements with latencies consistent with known vestibulo-spinal pathways. Furthermore, while the evoked head movements were substantially smaller than the coincidently evoked eye movements, they made a significant contribution to gaze stabilization, complementing the VOR to ensure that the appropriate gaze response is achieved. We speculate that analogous compensatory head movements will be evoked when implanted prosthetic devices are transitioned to human patients.

  5. Evaluation of renal function in rhesus monkeys and comparison to beagle dogs following oral administration of the organic acid triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid).

    Science.gov (United States)

    Timchalk, C; Finco, D R; Quast, J F

    1997-03-01

    The current study evaluated the effects of triclopyr (3,5, 6-trichloro-2-pyridinyloxyacetic acid) on renal function following oral administration in the beagle dog and rhesus monkey. Male rhesus monkeys were orally administered triclopyr by gavage at a dose of 5 mg/kg/day, 7 days/week for 28 days, after which the dosage was increased to 20 mg/kg/day for 102 consecutive days. Groups of male dogs were administered either a single oral dose of 5 mg/kg triclopyr or were fed a diet spiked with triclopyr at a dose of 5 mg/kg/day for 47 consecutive days. The following functional and clinical chemistry parameters were evaluated: exogenous phenolsulfonphthalein (PSP) excretion, inulin and para-aminohippurate (PAH) clearance (monkeys only), endogenous serum creatinine, and blood urea nitrogen (BUN) at multiple time points during the study. Creatinine, BUN, and inulin clearance were within the normal range from both species following triclopyr administration which indicates that repeated administration of triclopyr in the dog and monkey had no effect on glomerular filtration rate (GFR). In monkeys, the percentage excretion of PSP and PAH appeared to increase following triclopyr administration (20 mg/kg/day), suggesting that these weak organic acids may be competing for the same plasma protein-binding site enhancing their clearance. More importantly, these data strongly suggest that triclopyr is not competing with PSP or PAH for the active secretory site within the monkey kidney proximal tubules. In contrast, PSP clearance studies in dogs clearly demonstrated that triclopyr administration (5 mg/kg) can significantly decrease the percentage PSP excretion even following a single dose administration. The decrease in percentage PSP was reversible and inversely related to the plasma triclopyr concentration. Overall, these data clearly indicate that triclopyr effectively competes with PSP for the active secretory site within the dog kidney proximal tubules. In contrast, the monkey

  6. Decreases in electrocardiographic R-wave amplitude and QT interval predict myocardial ischemic infarction in Rhesus monkeys with left anterior descending artery ligation.

    Directory of Open Access Journals (Sweden)

    Xiaorong Sun

    Full Text Available Clinical studies have demonstrated the predictive values of changes in electrocardiographic (ECG parameters for the preexisting myocardial ischemic infarction. However, a simple and early predictor for the subsequent development of myocardial infarction during the ischemic phase is of significant value for the identification of ischemic patients at high risk. The present study was undertaken by using non-human primate model of myocardial ischemic infarction to fulfill this gap. Twenty male Rhesus monkeys at age of 2-3 years old were subjected to left anterior descending artery ligation. This ligation was performed at varying position along the artery so that it produced varying sizes of myocardial infarction at the late stage. The ECG recording was undertaken before the surgical procedure, at 2 h after the ligation, and 8 weeks after the surgery for each animal. The correlation of the changes in the ECG waves in the early or the late stage with the myocardial infarction size was analyzed. The R wave depression and the QT shortening in the early ischemic stage were found to have an inverse correlation with the myocardial infarction size. At the late stage, the R wave depression, the QT prolongation, the QRS score, and the ST segment elevation were all closely correlated with the developed infarction size. The poor R wave progression was identified at both the early ischemic and the late infarction stages. Therefore, the present study using non-human primate model of myocardial ischemic infarction identified the decreases in the R wave and the QT interval as early predictors of myocardial infarction. Validation of these parameters in clinical studies would greatly help identifying patients with myocardial ischemia at high risk for the subsequent development of myocardial infarction.

  7. Directed differentiation of rhesus monkey ES cells into pancreatic cell phenotypes

    Directory of Open Access Journals (Sweden)

    Nauert Brian

    2004-06-01

    Full Text Available Abstract Embryonic stem cells (ES can self-replicate and differentiate into all cell types including insulin-producing, beta-like cells and could, therefore, be used to treat diabetes mellitus. To date, results of stem cell differentiation into beta cells have been debated, largely due to difficulties in defining the identity of a beta cell. We have recently differentiated non-human primate (rhesus embryonic stem (rES cell lines into insulin producing, beta-like cells with the beta cell growth factor, Exendin-4 and using C-peptide as a phenotype marker. Cell development was characterized at each stage by gene and protein expression. Insulin, NKX6.1 and glucagon mRNA were expressed in stage 4 cells but not in early undifferentiated cells. We concluded that rES cells could be differentiated ex vivo to insulin producing cells. These differentiated rES cells could be used to develop a non-human primate model for evaluating cell therapy to treat diabetes. To facilitate the identification of beta-like cells and to track the cells post-transplantation, we have developed a marker gene construct: fusing the human insulin promoter (HIP to the green fluorescent protein (GFP gene. This construct was transfected into stage 3 rES derived cells and subsequent GFP expression was identified in C-peptide positive cells, thereby substantiating endogenous insulin production by rES derived cells. Using this GFP detection system, we will enrich our population of insulin producing rES derived cells and track these cells post-transplantation in the non-human primate model.

  8. Development of a Deltoid Shoulder Muscle Model for Rhesus Monkey Spaceflight Studies

    Science.gov (United States)

    Riley, Danny A.; Macias, Melissa Y.; Anders, Scott; Slocum, Glenn R.

    1995-01-01

    The acromiodeltoid shoulder muscle was demonstrated to be a suitable model for spaceflight studies. The muscle contains a mixture of fast and slow fibers, permitting analysis of muscle fiber type specific changes. Two biopsy sites per muscle were identified that provided samples not degraded by the biopsy procedure. Both sites contained sufficient numbers fibers for determining changes in fiber type percentages and size. There was adequate bilateral symmetry regarding fiber type composition in the left and right muscles such that a total of four times points can be compared. The ESOP cage did not cause atrophy of deltoid muscle fibers; this means that microgravity-induced atrophy should be detectable. As expected, muscle excision stimulated muscle IgM and IgG muscle autoantibody production. Nonrestrained control animals suppressed this response whereas restrained monkeys showed an abnormally pronounced response indicative a compromised immune system. The presence of ESOP cage-induced changes in the immune response may mask spaceflight-induced effects. The ESOP cage modified the dominant hand operation of the PTS. These results demonstrate the importance of high fidelity ground based controls.

  9. Age-related effects of estrogen on the expression of estrogen receptor (ER) α and β mRNA in the ovariectomized (OVX) monkey hypothalamus

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In the present study, we reported distribution of ERα and ER β mRNAs in the hypothalamus of young and old ovariectomized (OVX) rhesus macaques. The ERα were detected in all six major vestiblular nuclei which included arcuate nucleus (ARC) , paraventricularis nucleus (PVN) , periventricular nucleus (PeriV) , supraoptic nucleus (SON) ,medial prioptic nucleus (MPN) and lateral hypothalamus area (LHA). However, the ERβ mRNA can also detected in those nuclei excerpt SON, but the signals of ERβ mRNA were weaker than those of ERα mRNA. We observed that the degree of expression of ERs mRNA were different in most nucleus of old and young monkeys. The ERα mRNAs were highly expressed in ARC and SON in young monkeys compared with old monkeys. Moderate amount of ERα mRNAs hybridization signals and weak signals were observed in LHA, and MPN both in young and old monkeys. In contrast, only lower level of ERα hybridization signal were observed in PVN and PeriV in young monkeys, and the signals of ERα were very low in those nucleus of old monkeys. In general, the expression of ERβ mRNA were weaker than that of ERα mRNA in above nucleus excerpt LHA. The relatively higher density of ERβ hybridization signals have been observed in the LHA in young monkey compared with old monkeys. Low amount of ERβ mRNA hybridization signals were observed in the ARC, PVN and MPN, and no age differences were seen in PVN and MPN of those monkeys. In PeriV, we observed some signals in young monkey and a few signals in old monkeys. It was different from the rodent in which we did not found ERβ hybridization signal in SON. This study showed that both of the two estrogen receptors not only had the same pattern of expression but also had many different patterns of expression. The different expression of ERα and ERβ mRNAs in the young and old monkey brain may imply diverse functions in different regions of the monkey brain.

  10. Effects of calorie restriction on chromosomal stability in rhesus monkeys (Macaca mulatta)

    OpenAIRE

    Moore, Charleen M.; Dunn, Betty G.; McMahan, C. Alex; Lane, Mark A.; Roth, George S.; Ingram, Donald K.; Mattison, Julie A.

    2006-01-01

    The basic tenet of several theories on aging is increasing genomic instability resulting from interactions with the environment. Chromosomal aberrations have been used as classic examples of increasing genomic instability since they demonstrate an increase in numerical and structural abnormalities with age in many species including humans. This accumulating damage may augment many aging processes and initiate age-related diseases, such as neoplasias. Calorie restriction (CR) is one of the mos...

  11. Dose-response relationship for X-ray-induced reciprocal translocations in stem-cell spermatogonia of the rhesus monkey (macaca mulatta)

    International Nuclear Information System (INIS)

    The induction of reciprocal translocations in stem-cell spermatogonia of the rhesus monkey (Macaca mulatta) was studied after testicular X-irradiation of mature males (50, 100 and 200 rad) or whole-body irradiation of young males (200, and 300 rad). After the recovery of the germinal epithelium, cytogenetic analysis was carried out on spermatocytes descended from irradiated spermatogonia. Preparations of C-banded diakinesis-metaphase I were screened for translocation configurations. The frequencies of aberrations obtained were 0% at 0 rad, 0.36% at 50 rad, 0.86% at 100 rad, 0.99% at 200 rad and 0.68% at 300 rad, suggesting a humped dose-response relationship. There was no evidence for the contribution of a quadratic component to the yield in the lower dose range. A comparison of these results with those obtained for other mammals by a number of investigators shows that the frequencies of translocations in the rhesus monkey are much lower than those published for most other mammalian species. (orig.)

  12. A Golgi deimpregnation study of neurons in the rhesus monkey visual cortex (areas 17 and 18).

    Science.gov (United States)

    Werner, L; Winkelmann, E; Koglin, A; Neser, J; Rodewohl, H

    1989-01-01

    The morphological features of 298 neurons impregnated according to Golgi-Kopsch in areas 17 and 18 of Macaca mulatta were analyzed, and the same neurons were deimpregnated to visualize structural details of the somata in different types of neurons. The following cell types were investigated: Pyramidal and pyramid-like cells, spiny stellate cells, double bouquet cells, bipolar cells, chandelier cells, neurogliaform cells, basket and related cells. This procedure allows the evaluation of the nuclear-cytoplasmic proportion and the position of the nucleus besides shape and size of the cell body. Pyramidal and pyramid-like cells (N = 43), spiny stellate cells (N = 26), basket and related cells (N = 126) are variable in these features. A positive correlation between soma size and width of the cytoplasm is found in pyramidal, pyramid-like cells and spiny stellate cells. With the exception of some large somata in both these types of neurons the nucleus is found in a central position. Double bouquet cells (N = 6), bipolar cells (N = 13) and chandelier cells (N = 11) exhibit small cytoplasmic rims and centrally located nuclei. The small somata of neurogliaform cells (N = 37), however, and the small to very large somata of basket and related cells show broad cytoplasmic portions surrounding the eccentrically located nuclei. These findings allow the identification of different neuronal types in Nissl-stained sections on the basis of these soma features. This is a prerequisite for further detailed quantitative studies on the laminar distribution of different neuronal types in the visual cortex of the monkey. PMID:2610391

  13. IBI302, a promising candidate for AMD treatment, targeting both the VEGF and complement system with high binding affinity in vitro and effective targeting of the ocular tissue in healthy rhesus monkeys.

    Science.gov (United States)

    Ren, Xinyi; Li, Jia; Xu, Xianxing; Wang, Chunming; Cheng, Yuanguo

    2016-04-01

    Uncontrolled activation of complement and upregulation of vascular endothelial growth factor (VEGF) play fundamental roles in age-related macular degeneration (AMD). However, most drugs used to treat AMD focus on a single target, and the percentage of effectively treated patients in clinical practice needs to be improved. Therefore, novel AMD treatment approaches are needed. IBI302 is a novel bispecific decoy receptor fusion protein designed with both a VEGF inhibition domain and a complement cascade inhibition domain, which are connected by the Fc region of human immunoglobulin. In this study, we systematically evaluated the binding affinity between IBI302 and VEGF isoforms and complement proteins by using surface plasmon resonance (SPR) technology. Anti-VEGF blockers (aflibercept and bevacizumab) and complement receptor 1 were used as references. The SPR assay results indicated that IBI302 could bind different VEGF isoforms and complement proteins with high affinity. The biological activity of IBI302 was also studied. IBI302 showed an inhibitory effect on human primary umbilical vein endothelial cell proliferation and the activation of complement pathways in vitro. Finally, the pharmacokinetic (PK) properties of IBI302 were evaluated in rhesus monkeys. The PK results showed that after a 0.5 mg/eye intravitreal dosage, IBI302 became rapidly distributed from the vitreous humor into targeted tissues and remained active over 504 h. Overall, the favorable anti-angiogenic and anti-complement effects of IBI302 along with the good PK profiles in rhesus monkeys support the selection and development of IBI302 as a promising candidate for AMD treatment. PMID:26919788

  14. Age-dependent changes in innate immune phenotype and function in rhesus macaques (Macaca mulatta)

    OpenAIRE

    Asquith, Mark; Haberthur, Kristen; Brown, Monica; Engelmann, Flora; Murphy, Ashleigh; Al-Mahdi, Zainab; Messaoudi, Ilhem

    2012-01-01

    Aged individuals are more susceptible to infections due to a general decline in immune function broadly referred to as immune senescence. While age-related changes in the adaptive immune system are well documented, aging of the innate immune system remains less well understood, particularly in nonhuman primates. A more robust understanding of age-related changes in innate immune function would provide mechanistic insight into the increased susceptibility of the elderly to infection. Rhesus ma...

  15. Inducible nitric oxide synthase in heart tissue and nitric oxide in serum of Trypanosoma cruzi-infected rhesus monkeys: association with heart injury.

    Directory of Open Access Journals (Sweden)

    Cristiano Marcelo Espinola Carvalho

    Full Text Available BACKGROUND: The factors contributing to chronic Chagas' heart disease remain unknown. High nitric oxide (NO levels have been shown to be associated with cardiomyopathy severity in patients. Further, NO produced via inducible nitric oxide synthase (iNOS/NOS2 is proposed to play a role in Trypanosoma cruzi control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, using chronically infected rhesus monkeys and iNOS/NOS2-deficient (Nos2(-/- mice we explored the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection. METHODOLOGY: Rhesus monkeys and C57BL/6 and Nos2(-/- mice were infected with the Colombian T. cruzi strain. Parasite DNA was detected by polymerase chain reaction, T. cruzi antigens and iNOS/NOS2(+ cells were immunohistochemically detected in heart sections and NO levels in serum were determined by Griess reagent. Heart injury was assessed by electrocardiogram (ECG, echocardiogram (ECHO, creatine kinase heart isoenzyme (CK-MB activity levels in serum and connexin 43 (Cx43 expression in the cardiac tissue. RESULTS: Chronically infected monkeys presented conduction abnormalities, cardiac inflammation and fibrosis, which resembled the spectrum of human chronic chagasic cardiomyopathy (CCC. Importantly, chronic myocarditis was associated with parasite persistence. Moreover, Cx43 loss and increased CK-MB activity levels were primarily correlated with iNOS/NOS2(+ cells infiltrating the cardiac tissue and NO levels in serum. Studies in Nos2(-/- mice reinforced that the iNOS/NOS2-NO pathway plays a pivotal role in T. cruzi-elicited cardiomyocyte injury and in conduction abnormalities that were associated with Cx43 loss in the cardiac tissue. CONCLUSION: T. cruzi-infected rhesus monkeys reproduce features of CCC. Moreover, our data support that in T. cruzi infection persistent parasite-triggered iNOS/NOS2 in the cardiac tissue and NO overproduction might contribute

  16. Analysis on Pathology of Lung Lesion in Captive Rhesus Monkey%人工饲养条件下死亡恒河猴肺脏病理改变分析

    Institute of Scientific and Technical Information of China (English)

    赵玺龙; 杨举伦; 王力; 李峰; 赵稳兴; 李涛; 王丽; 杨丽琳; 陈玥

    2011-01-01

    Objective To observe the pathology changes in lungs lesions of captive rhesus monkey, explore the distribution rule and pathological features of diseases in respiratory system.Methods We postmortem 155 nature dead monkeys from 2 ~ 20 years which were bred in institutes in Yunnan provinces.Monkeys were divided into young, adult and aged groups according to their age.The pathology changes of lung were investigated by routine histopathological technique and the analysis of chi-square test was performed.Results Of 155 monkeys, 59 samples have lung lesions, the ratio was 38.06%.the main lesion include pulmonary edema, intralveolar hemorrhage, lobar pneumonia, alveolar organization,lobular pneumonia, chronic bronchitis, bronchiectasis, interstitial pneumonia, granulomatosis of lung, emphysema,pulmonary abscess, pleurisy.The kinds and the frequency of lesions are different in different age groups.Conclusions The incidence rates of diseases of lung of breeding rhesus macaques is higher and its interference effect should be seriously taken.Some pathological changes of lung are different in diverse age groups.The results of our test enrich the data of the captive monkeys,and it is useful in quality control of captive monkeys and animal tests.%目的 观察人工饲养条件下实验恒河猴肺脏病理改变,探讨实验猴呼吸系统疾病分布规律和病理改变特点,丰富实验猴自发病变基本研究资料.方法 对1998~2008年云南地区饲养的自然死亡的155只恒河猴(年龄2~20岁)的肺脏进行病理检查,按年龄分为幼年组、成年组、老年组,并对观察结果进行统计学分析.结果 实验猴肺脏主要病变有大叶性肺炎、支气管肺炎、间质性肺炎、肺气肿、支气管扩张症、胸膜炎、肺肉芽肿性炎等12种,出现率最高的为支气管肺炎(18.71%)和大叶性肺炎(16.74%).恒河猴肺脏病变在不同年龄阶段均有发生,老年猴组肺脏病变发生率最高,疾病类型和发生

  17. Potenciales evocados auditivos del tallo cerebral en monos rhesus (Macaca mulatta en diferentes etapas fisiológicas en condiciones de cautiverio Brainstem's auditory evoked potentials in rhesus monkeys (Macaca mulatta in different physiologic stages under captivity

    Directory of Open Access Journals (Sweden)

    A Ibáñez-Contreras

    2011-01-01

    ,2-6,1 year old; Group 3 (6,2-9,1 year old; Group 4 (9,2-12,1 year old and Group 5 (12,2-27,1 years and older. The BAEP were obtained by the stimulation of the ear with rarefaction “clicks” of 50 dB of intensity. The cerebral electric activity was picked up by gold disc electrodes, placed in the Cz (+, A1, A2 (- and Fz derivations as land, according to the 10/20 international system. Four waves were detected in the five evaluated groups. Since no significant differences were found in the ANOVAs by separated afferences, an ANOVA of united afferences was done. It was observed that groups 1 and 5 provided significant differences in all evaluated waves, showing the extended latencies in relation to other groups. It was concluded that BAEP made it possible to identify changes that are generated from the development, maturation and aging in rhesus monkeys.

  18. Behavioral inhibition in rhesus monkeys (Macaca mulatta is related to the airways response, but not immune measures, commonly associated with asthma.

    Directory of Open Access Journals (Sweden)

    Katie Chun

    Full Text Available Behavioral inhibition reflects a disposition to react warily to novel situations, and has been associated with atopic diseases such as asthma. Retrospective work established the relationship between behavioral inhibition in rhesus monkeys (Macaca mulatta and airway hyperresponsiveness, but not atopy, and the suggestion was made that behavioral inhibition might index components of asthma that are not immune-related. In the present study, we prospectively examined the relationship between behavioral inhibition and airway hyperresponsiveness, and whether hormonal and immune measures often associated with asthma were associated with behavioral inhibition and/or airway hyperresponsiveness. In a sample of 49 yearling rhesus monkeys (mean=1.25 years, n=24 behaviorally inhibited animals, we measured in vitro cytokine levels (IL-4, IL-10, IL-12, IFN-γ in response to stimulation, as well as peripheral blood cell percentages, cortisol levels, and percentage of regulatory T-cells (CD3+CD4+CD25+FOXP3+. Airway reactivity was assessed using an inhaled methacholine challenge. Bronchoalveolar lavage was performed and the proportion of immune cells was determined. Behaviorally inhibited monkeys had airway hyperresponsiveness as indicated by the methacholine challenge (p=0.031, confirming our earlier retrospective result. Airway hyperresponsiveness was also associated with lower lymphocyte percentages in lavage fluid and marginally lower plasma cortisol concentrations. However, none of the tested measures was significantly related to both behavioral inhibition and airway hyperresponsiveness, and so could not mediate their relationship. Airway hyperresponsiveness is common to atopic and non-atopic asthma and behavioral inhibition has been related to altered autonomic activity in other studies. Our results suggest that behavioral inhibition might index an autonomically mediated reactive airway phenotype, and that a variety of stimuli (including inflammation within

  19. The Physiological Effect of Human Grooming on the Heart Rate and the Heart Rate Variability of Laboratory Non-Human Primates: A Pilot Study in Male Rhesus Monkeys.

    Science.gov (United States)

    Grandi, Laura Clara; Ishida, Hiroaki

    2015-01-01

    Grooming is a widespread, essential, and complex behavior with social and affiliative valence in the non-human primate world. Its impact at the autonomous nervous system level has been studied during allogrooming among monkeys living in a semi-naturalistic environment. For the first time, we investigated the effect of human grooming to monkey in a typical experimental situation inside laboratory. We analyzed the autonomic response of male monkeys groomed by a familiar human (experimenter), in terms of the heart rate (HR) and heart rate variability (HRV) at different body parts. We considered the HRV in both the time (SDNN, RMSSD, and RMSSD/SDNN) and the frequency domain (HF, LF, and LF/HF). For this purpose, we recorded the electrocardiogram of two male rhesus monkeys seated in a primate chair while the experimenter groomed their mouth, chest, or arm. We demonstrated that (1) the grooming carried out by a familiar human determined a decrement of the HR and an increment of the HRV; (2) there was a difference in relation to the groomed body part. In particular, during grooming the mouth the HRV was higher than during grooming the arm and the chest. Taken together, the results represent the first evidence that grooming carried out by a familiar human on experimental monkeys has the comparable positive physiological effect of allogrooming between conspecifics. Moreover, since the results underlined the positive modulation of both HR and HRV, the present study could be a starting point to improve the well-being of non-human primates in experimental condition by means of grooming by a familiar person. PMID:26664977

  20. Limited replication of yellow fever 17DD and 17D-Dengue recombinant viruses in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Gisela F. Trindade

    2008-06-01

    Full Text Available For the development of safe live attenuated flavivirus vaccines one of the main properties to be established is viral replication. We have used real-time reverse transcriptase-polymerase chain reaction and virus titration by plaque assay to determine the replication of yellow fever 17DD virus (YFV 17DD and recombinant yellow fever 17D viruses expressing envelope proteins of dengue virus serotypes 2 and 4 (17D-DENV-2 and 17D-DENV-4. Serum samples from rhesus monkeys inoculated with YFV 17DD and 17D-DENV chimeras by intracerebral or subcutaneous route were used to determine and compare the viremia induced by these viruses. Viral load quantification in samples from monkeys inoculated by either route with YFV 17DD virus suggested a restricted capability of the virus to replicate reaching not more than 2.0 log10 PFU mL-1 or 3.29 log10 copies mL-1. Recombinant 17D-dengue viruses were shown by plaquing and real-time PCR to be as attenuated as YF 17DD virus with the highest mean peak titer of 1.97 log10 PFU mL-1 or 3.53 log10 copies mL-1. These data serve as a comparative basis for the characterization of other 17D-based live attenuated candidate vaccines against other diseases.Uma das principais propriedades a serem estabelecidas para o desenvolvimento de vacinas seguras e atenuadas de flavivirus,é a taxa de replicação viral. Neste trabalho, aplicamos a metodologia de amplificação pela reação em cadeia da polimerase em tempo real e titulação viral por plaqueamento para determinação da replicação do vírus 17DD (FA 17DD e recombinantes, expressando proteínas do envelope de dengue sorotipos 2 e 4 (17D-DENV-2 e 17D-DENV-4. As amostras de soros de macacos inoculados por via intracerebral ou subcutânea com FA 17DD ou 17D-DENV foram usadas para determinar e comparar a viremia induzida por estes vírus. A quantificação da carga viral em amostras de macacos inoculados por ambas as vias com FA 17DD sugere restrita capacidade de replicação com

  1. Study of the safety, immunogenicity and efficacy of attenuated and killed Leishmania (Leishmania major vaccines in a rhesus monkey (Macaca mulatta model of the human disease

    Directory of Open Access Journals (Sweden)

    VF Amaral

    2002-10-01

    Full Text Available We have compared the efficacy of two Leishmania (Leishmania major vaccines, one genetically attenuated (DHFR-TS deficient organisms, the other inactivated [autoclaved promastigotes (ALM with bacillus Calmete-Guérin (BCG], in protecting rhesus macaques (Macaca mulatta against infection with virulent L. (L. major. Positive antigen-specific recall proliferative response was observed in vaccinees (79% in attenuated parasite-vaccinated monkeys, versus 75% in ALM-plus-BCG-vaccinated animals, although none of these animals exhibited either augmented in vitro gamma interferon (IFN-g production or positive delayed-type hypersensitivity (DTH response to the leishmanin skin test prior to the challenge. Following challenge, there were significant differences in blastogenic responses (p < 0.05 between attenuated-vaccinated monkeys and naïve controls. In both vaccinated groups very low levels of antibody were found before challenge, which increased after infective challenge. Protective immunity did not follow vaccination, in that monkeys exhibited skin lesion at the site of challenge in all the groups. The most striking result was the lack of pathogenicity of the attenuated parasite, which persisted in infected animals for up to three months, but were incapable of causing disease under the conditions employed. We concluded that both vaccine protocols used in this study are safe in primates, but require further improvement for vaccine application.

  2. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on signal transduction pathway-related protein expression in liver and cerebrum of rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Ohta, Mari; Akema, Satoshi; Tsuzuki, Masami; Kubota, Shunichiro [Tokyo Univ. (Japan); Korenaga, Tatsumi; Fukusato, Toshio [Teikyo Univ. of School of Medicine, Tokyo (Japan); Asaoka, Kazuo [Kyoto Univ. (Japan); Murata, Nobuo [Teikyo Univ. of School of Medicine, Kawasaki (Japan); Nomizu, Motoyoshi [Hokkaido Univ., Sapporo (Japan); Arima, Akihiro [Shin Nippon Biomedical Laboratories, Ltd., Kagoshima (Japan)

    2004-09-15

    2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to produce a wide range of toxic and biochemical effects in experimental animals, including immunological dysfunctions, chloracne, tetragenecity and carcinogenesis. Recently, the potential impact of dioxins on neurological disorders with particular focus on attention deficit hyperactivity disorder (ADHD) are concerned. Although a lot of information is available from studies in rodents, not much is known of the low dose effects of TCDD in non-human primates. In higher animals, dioxins are metabolized slowly, as evidenced by the estimated TCDD half-life of 5.8 to 14.1 years. Therefore, it is necessary to investigate the long-term effects of TCDD on human health. Considering the pronounced species differences observed in some studies of TCDD, the studies using primates are needed for assessment of TCDD exposure on human health. We have been studying the metabolism and the effects of single administration of TCDD on pregnant monkey (F0) and F1 rhesus monkey. The focus of the present study is to study the effects of TCDD on signal transduction pathway-related protein levels in various organs, especially in liver and brain of F0 monkeys.

  3. Brain kinetics of 11 C-labelled L-tryptophan and 5-hydroxy-L-tryptophan in the Rhesus monkey. A study using positron emission tomography

    International Nuclear Information System (INIS)

    5-hydroxy-L-tryptophan labelled with 11 C is introduced as a tracer for the vivo assessment of brain serotonin synthesis in the Rhesus monkey using positron emission tomography, PET. Increasing radioactivities were seen in the striatal area in contrast to that seen in other brain regions. Following 11 C-labelled L-tryptophan an even spread of brain radioactivity was seen. This selective increase most probably results from the decarboxylation of tracer and retention of formed products since no striatal increase of radioactivity was seen when 5-hydroxy-L-tryptophan labelled with 11 C in the carboxy-position was administered. Furthermore, pretreatment of the monkey with a centrally active decarboxylase inhibitor (NSD 1015, 10 mg/kg) did not lead to increased striatal radioactivities after the administration of 5-hydroxy-(β-11 C)-L-tryptophan. The selective utilization of the radiotracer in the striatal area increased with a rate constant calculated to be 0.0055 ± 0.0015 min-1 (n=5) using the surrounding brain as reference area. A non-significant influence of radiolabelled metabolites to the rate constants measured was shown after pretreatment of the monkeys with selective and non-selective monoamine oxidase inhibitors, respectively. These results may give a basis for the use of the new tracer 5-hydroxy-(β-11 C)-L-tryptophan in PET-studies of brain serotonin metabolism in health and disease. (authors)

  4. Pharmacokinetics of triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid) in the beagle dog and rhesus monkey: perspective on the reduced capacity of dogs to excrete this organic acid relative to the rat, monkey, and human.

    Science.gov (United States)

    Timchalk, C; Nolan, R J

    1997-06-01

    The pharmacokinetics of triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid) were measured in the beagle dog and rhesus monkey and compared with the kinetics observed in rats and humans. In addition, studies were conducted in anesthetized dogs to better understand the mechanism by which [14C]triclopyr is eliminated in this species. Triclopyr was dissolved in distilled water, and administered as a single oral dose of 0.5, 5, or 20 mg/kg to three male dogs. A single male rhesus monkey was given an intravenous dose of 30 mg [14C]triclopyr/kg body wt on two occasions separated by 10 days. Anesthetized male dogs, were implanted with venous, arterial, and urethral catheters and given increasing amounts of triclopyr to produce plasma triclopyr levels ranging from 0.3 to 27 microg eq/mL. In the monkey, triclopyr was rapidly eliminated from the plasma (t1/2 = 6.3 hr) with >95% of the urinary 14C activity excreted within 24 hr postdosing. In the dog, orally administered triclopyr was rapidly and effectively absorbed at every dose level with virtually all of it excreted in the urine by 72 hr postdosing. However, the kinetics were slightly nonlinear, and the fraction of the dose excreted in the urine decreased with increasing dose. Several nonlinear processes may collectively contribute to the modest nonlinear pharmacokinetics in the dog. Plasma protein binding of triclopyr in the dog ranged from 94 to 99%, was nonlinear, and was an important determinant in the renal clearance of triclopyr. The nonlinear plasma protein binding indicates that glomerular filtration became disproportionately more important as plasma triclopyr concentration increased. There was good evidence for a high-affinity low-capacity active-secretory process that was saturated by low plasma triclopyr concentrations. As plasma triclopyr concentrations increased, tubular reabsorption begins to exceed secretion, resulting in decreased renal clearance. The volume of distribution, normalized for body weight

  5. A 4-channel 3 Tesla phased array receive coil for awake rhesus monkey fMRI and diffusion MRI experiments

    OpenAIRE

    Khachaturian, Mark Haig

    2010-01-01

    Awake monkey fMRI and diffusion MRI combined with conventional neuroscience techniques has the potential to study the structural and functional neural network. The majority of monkey fMRI and diffusion MRI experiments are performed with single coils which suffer from severe EPI distortions which limit resolution. By constructing phased array coils for monkey MRI studies, gains in SNR and anatomical accuracy (i.e., reduction of EPI distortions) can be achieved using parallel imaging. The major...

  6. Effect of spaceflight on the maximal shortening velocity, morphology, and enzyme profile of fast- and slow-twitch skeletal muscle fibers in rhesus monkeys

    Science.gov (United States)

    Fitts, R. H.; Romatowski, J. G.; De La Cruz, L.; Widrick, J. J.; Desplanches, D.

    2000-01-01

    Weightlessness has been shown to cause limb muscle wasting and a reduced peak force and power in the antigravity soleus muscle. Despite a reduced peak power, Caiozzo et al. observed an increased maximal shortening velocity in the rat soleus muscle following a 14-day space flight. The major purpose of the present investigation was to determine if weightlessness induced an elevated velocity in the antigravity slow type I fibers of the rhesus monkey (Macaca mulatta), as well as to establish a cellular mechanism for the effect. Spaceflight or models of weightlessness have been shown to increase glucose uptake, elevate muscle glycogen content, and increase fatigability of the soleus muscle. The latter appears to be in part caused by a reduced ability of the slow oxidative fibers to oxidize fats. A second goal of this study was to establish the extent to which weightlessness altered the substrate profile and glycolytic and oxidative enzyme capacity of individual slow- and fast-twitch fibers.

  7. Acute and late effects of 16- and 50-MeV/sub d → Be/ neutrons on the oral mucosa of Rhesus monkeys

    International Nuclear Information System (INIS)

    Twenty-five rhesus monkeys were randomly assigned to one of five mouth irradiation treatment schedules: control group, no irradiation; 60Co γ five times weekly; 60Co twice weekly; 16-MeV/sub d→Be/ neutrons twice weekly. Although the acute reactions of the oral mucosa were similar in the four irradiated groups, the late sequelae were more severe in the animals irradiated twice weekly with 60Co γ or neutrons. All of the animals irradiated with 60Co γ twice weekly or with 16 MeV/sub d→Be/ neutrons exhibited oromucosal necrosis, whereas none of those irradiated five times weekly with 60Co γ did. The difference in the effect of photon fractionation on early and late radiation sequelae may be related to different patterns of redistribution of surviving cells through the division cycle in tissues responsible for early and late damage. (auth)

  8. Effects of damage to the suprachiasmatic area of the anterior hypothalamus on the daily melatonin and cortisol rhythms in the rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Reppert, S.M.; Perlow, M.J.; Ungerleider, L.G.; Mishkin, M.; Tamarkin, L.; Orloff, D.G.; Hoffman, H.J.; Klein, D.C.

    1981-12-01

    The effects of lesions of the suprachiasmatic nucleus (SCN) on the circadian rhythms in melatonin and cortisol were examined in the rhesus monkey. The concentrations of the two hormones were monitored in cerebrospinal fluid (CSF) withdrawn from two sham-operated animals, two animals with complete bilateral SCN lesions, and two animals with partial SCN damage at 4 and 8 months after surgery. In the sham-operated animals, as in the intact animal, the daily melatonin rhythm was entrained to the daily light-dark cycle, was suppressed in constant light, and persisted in constant darkness. In contrast, neither animal with complete SCN ablation exhibited a daily pattern of CSF melatonin in diurnal lighting at 4 months after surgery nor were their melatonin levels at constant low values. Furthermore, CSF melatonin concentrations were not suppressed in either animal by constant light. Surprisingly, at 8 months after surgery, spectral analysis revealed a 24-hr component to the melatonin patterns for each animal with complete SCN ablation in both diurnal lighting and constant darkness. The two animals with partial SCN damage exhibited a daily melatonin rhythm in diurnal lighting, but constant light did not suppress CSF melatonin concentrations consistently. Daily rhythms persisted in both for a 6 1/2-d period of study in constant darkness. In contrast to the alterations in the melatonin rhythm after SCN damage, there was no apparent effect of either partial or complete SCN ablation on the daily CSF cortisol rhythm. These data indicate that, in the rhesus monkey, the SCN is important for the generation, photic entrainment, and photic suppression of the melatonin rhythm. However, circadian oscillators located outside of the SCN region may control the normal daily cortisol rhythm and perhaps the melatonin rhythm in the absence of the SCN.

  9. Effects of damage to the suprachiasmatic area of the anterior hypothalamus on the daily melatonin and cortisol rhythms in the rhesus monkey

    International Nuclear Information System (INIS)

    The effects of lesions of the suprachiasmatic nucleus (SCN) on the circadian rhythms in melatonin and cortisol were examined in the rhesus monkey. The concentrations of the two hormones were monitored in cerebrospinal fluid (CSF) withdrawn from two sham-operated animals, two animals with complete bilateral SCN lesions, and two animals with partial SCN damage at 4 and 8 months after surgery. In the sham-operated animals, as in the intact animal, the daily melatonin rhythm was entrained to the daily light-dark cycle, was suppressed in constant light, and persisted in constant darkness. In contrast, neither animal with complete SCN ablation exhibited a daily pattern of CSF melatonin in diurnal lighting at 4 months after surgery nor were their melatonin levels at constant low values. Furthermore, CSF melatonin concentrations were not suppressed in either animal by constant light. Surprisingly, at 8 months after surgery, spectral analysis revealed a 24-hr component to the melatonin patterns for each animal with complete SCN ablation in both diurnal lighting and constant darkness. The two animals with partial SCN damage exhibited a daily melatonin rhythm in diurnal lighting, but constant light did not suppress CSF melatonin concentrations consistently. Daily rhythms persisted in both for a 6 1/2-d period of study in constant darkness. In contrast to the alterations in the melatonin rhythm after SCN damage, there was no apparent effect of either partial or complete SCN ablation on the daily CSF cortisol rhythm. These data indicate that, in the rhesus monkey, the SCN is important for the generation, photic entrainment, and photic suppression of the melatonin rhythm. However, circadian oscillators located outside of the SCN region may control the normal daily cortisol rhythm and perhaps the melatonin rhythm in the absence of the SCN

  10. Effects of age on latency and variability of visual response in monkeys

    Institute of Scientific and Technical Information of China (English)

    YU Shan; WANG Xiusong; FU Yu; ZHANG Jie; MA Yuanye; WANG Yongchang; ZHOU Yifeng

    2005-01-01

    @@ Visual function declines during normal aging[1]. The neural mechanisms underlying age-related changes have retinal ganglion cells and cells in dorsal lateral geniculate nucleus(dLGN)in old monkeys are relatively normal[1,2].

  11. Three-dimensional organization of otolith-ocular reflexes in rhesus monkeys. II. Inertial detection of angular velocity

    Science.gov (United States)

    Angelaki, D. E.; Hess, B. J.

    1996-01-01

    1. The dynamic contribution of otolith signals to three-dimensional angular vestibuloocular reflex (VOR) was studied during off-vertical axis rotations in rhesus monkeys. In an attempt to separate response components to head velocity from those to head position relative to gravity during low-frequency sinusoidal oscillations, large oscillation amplitudes were chosen such that peak-to-peak head displacements exceeded 360 degrees. Because the waveforms of head position and velocity differed in shape and frequency content, the particular head position and angular velocity sensitivity of otolith-ocular responses could be independently assessed. 2. During both constant velocity rotation and low-frequency sinusoidal oscillations, the otolith system generated two different types of oculomotor responses: 1) modulation of three-dimensional eye position and/or eye velocity as a function of head position relative to gravity, as presented in the preceding paper, and 2) slow-phase eye velocity as a function of head angular velocity. These two types of otolith-ocular responses have been analyzed separately. In this paper we focus on the angular velocity responses of the otolith system. 3. During constant velocity off-vertical axis rotations, a steady-state nystagmus was elicited that was maintained throughout rotation. During low-frequency sinusoidal off-vertical axis oscillations, dynamic otolith stimulation resulted primarily in a reduction of phase leads that characterize low-frequency VOR during earth-vertical axis rotations. Both of these effects are the result of an internally generated head angular velocity signal of otolithic origin that is coupled through a low-pass filter to the VOR. No change in either VOR gain or phase was observed at stimulus frequencies larger than 0.1 Hz. 4. The dynamic otolith contribution to low-frequency angular VOR exhibited three-dimensional response characteristics with some quantitative differences in the different response components. For

  12. Autophagic Killing Effects against Mycobacterium tuberculosis by Alveolar Macrophages from Young and Aged Rhesus Macaques

    OpenAIRE

    Pacheco, Sophia A.; Powers, Katelyn M.; Engelmann, Flora; Messaoudi, Ilhem; Purdy, Georgiana E.

    2013-01-01

    Non-human primates, notably rhesus macaques (Macaca mulatta, RM), provide a robust experimental model to investigate the immune response to and effective control of Mycobacterium tuberculosis infections. Changes in the function of immune cells and immunosenescence may contribute to the increased susceptibility of the elderly to tuberculosis. The goal of this study was to examine the impact of age on M. tuberculosis host-pathogen interactions following infection of primary alveolar macrophages...

  13. Different sensitivities to competitive inhibition of benzodiazepine receptor binding of {sup 11}C-iomazenil and {sup 11}C-flumazenil in rhesus monkey brain

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Osamu; Hosoi, Rie; Kobayashi, Kaoru [Osaka Univ., Suita (Japan). Medical School; Itoh, Takashi; Gee, A.; Suzuki, Kazutoshi

    2001-04-01

    The in vivo binding kinetics of {sup 11}C-iomazenil were compared with those of {sup 11}C-flumazenil binding in rhesus monkey brain. The monkey was anesthetized with ketamine and intravenously injected with either {sup 11}C-iomazenil or {sup 11}C-flumazenil in combination with the coadministration of different doses of non-radioactive flumazenil (0, 5 and 20 {mu}g/kg). The regional distribution of {sup 11}C-iomazenil in the brain was similar to that of {sup 11}C-flumazenil, but the sensitivity of {sup 11}C-iomazenil binding to competitive inhibition by non-radioactive flumazenil was much less than that of {sup 11}C-flumazenil binding. A significant reduction in {sup 11}C-flumazenil binding in the cerebral cortex was observed with 20 {mu}g/kg of flumazenil, whereas a relatively smaller inhibition of {sup 11}C-iomazenil binding in the same region was observed with the same dose of flumazenil. These results suggest that {sup 11}C-flumazenil may be a superior radiotracer for estimating benzodiazepine receptor occupancy in the intact brain. (author)

  14. Directional character of spreading of vasogenic cerebral edema after radiation damage in rhesus monkeys, and effects of removal of the primary lesion

    International Nuclear Information System (INIS)

    Five pubescent rhesus monkeys were exposed to 35 Gy of orthovoltage x-irradiation in a single dose to the right visual cortex. Twenty to 36 weeks later the irradiated region broke down rather abruptly. Steep rise of cerebrospinal fluid (CSF) protein and lactic dehydrogenase (LDH) indicated disruption of blood brain barrier (BBB) and tissue breakdown. Visual evoked response (VER), funduscopic and clinical findings suggested disfunction of neural tissues and increased intracranial pressure. Extraordinary brain swelling and distortion were observed at the time of sacrifice. The most striking finding was that the ipsilateral middle and inferior temporal gyri, where radiation did not affect directly, were selectively swollen and edematous sparing the superior temporal gyrus. Corticocortical neuronal connections between visual cortex and inferior convexity of the temporal lobe has been demonstrated by Kuypers et al. Our previous studies also disclosed selective swelling of other remote visual association areas, i. e., ipsilateral lateral geniculate body and uncinate fasciculus. Thus, edema fluid might propagate from the site of the lesion through the anatomic pathways. In the group of monkeys, which received surgical removals of damaged right occipital lobes where BBB was disrupted, CSF protein and LDH drastically returned to the normal base line values after the surgery. Furthermore, no swelling of ipsilateral middle and inferior temporal gyri was observed in this group at the time of sacrifice, indicating that spreaded vasogenic edema could be subdued by removing the primary lesion. (author)

  15. Different sensitivities to competitive inhibition of benzodiazepine receptor binding of 11C-iomazenil and 11C-flumazenil in rhesus monkey brain

    International Nuclear Information System (INIS)

    The in vivo binding kinetics of 11C-iomazenil were compared with those of 11C-flumazenil binding in rhesus monkey brain. The monkey was anesthetized with ketamine and intravenously injected with either 11C-iomazenil or 11C-flumazenil in combination with the coadministration of different doses of non-radioactive flumazenil (0, 5 and 20 μg/kg). The regional distribution of 11C-iomazenil in the brain was similar to that of 11C-flumazenil, but the sensitivity of 11C-iomazenil binding to competitive inhibition by non-radioactive flumazenil was much less than that of 11C-flumazenil binding. A significant reduction in 11C-flumazenil binding in the cerebral cortex was observed with 20 μg/kg of flumazenil, whereas a relatively smaller inhibition of 11C-iomazenil binding in the same region was observed with the same dose of flumazenil. These results suggest that 11C-flumazenil may be a superior radiotracer for estimating benzodiazepine receptor occupancy in the intact brain. (author)

  16. Low- and high-frequency transcutaneous electrical acupoint stimulation induces different effects on cerebral μ-opioid receptor availability in rhesus monkeys.

    Science.gov (United States)

    Xiang, Xiao-Hui; Chen, Ying-Mao; Zhang, Jin-Ming; Tian, Jia-He; Han, Ji-Sheng; Cui, Cai-Lian

    2014-05-01

    Although systematic studies have demonstrated that acupuncture or electroacupuncture (EA) analgesia is based on their accelerating endogenous opioid release to activate opioid receptors and that EA of different frequencies is mediated by different opioid receptors in specific areas of the central nervous system, there is little direct, real-time evidence to confirm this in vivo. The present study was designed to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS), an analogue of EA, at low and high frequencies on μ-opioid receptor (MOR) availability in the brain of rhesus monkeys. Monkeys underwent 95-min positron emission tomography (PET) with (11) C-carfentanil three times randomly while receiving 0, 2, or 100 Hz TEAS, respectively. Each TEAS was administered in the middle 30 min during the 95-min PET scan, and each session of PET and TEAS was separated by at least 2 weeks. The results revealed that 2 Hz but not 100 Hz TEAS evoked a significant increase in MOR binding potential in the anterior cingulate cortex, the caudate nucleus, the putamen, the temporal lobe, the somatosensory cortex, and the amygdala compared with 0 Hz TEAS. The effect remained after the end of TEAS in the anterior cingulate cortex and the temporal lobe. The selective increase in MOR availability in multiple brain regions related to pain and sensory processes may play a role in mediating low-frequency TEAS efficacy. PMID:24482187

  17. Protective Effects of High Ambient Lighting on the Development of Form-Deprivation Myopia in Rhesus Monkeys

    OpenAIRE

    Smith, Earl L.; Hung, Li-Fang; Huang, Juan

    2012-01-01

    This study shows that high ambient lighting retards the development of vision-induced myopia in infant monkeys. The results suggest that the protective effects of outdoor activities against myopia in children are due to exposure to high light levels.

  18. Age-Related Neurochemical Changes in the Rhesus Macaque Cochlear Nucleus

    OpenAIRE

    Gray, Daniel T.; Engle, James R.; Recanzone, Gregg H.

    2014-01-01

    Neurochemical changes in the expression of various proteins within the central auditory system have been associated with natural aging. These changes may compensate in part for the loss of auditory sensitivity arising from two phenomena of the aging auditory system: cochlear histopathologies and increased excitability of central auditory neurons. Recent studies in the macaque monkey have revealed age-related changes in the density of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphor...

  19. Early adverse rearing experiences alter sleep-wake patterns and plasma cortisol levels in juvenile rhesus monkeys

    OpenAIRE

    Barrett, Catherine E; Noble, Pamela; Hanson, Erin; Pine, Daniel S.; Winslow, James T.; Nelson, Eric E.

    2009-01-01

    Monkeys separated from their mothers soon after birth and raised with peers display many disturbances in emotional behavior that are similar to human mood and anxiety disorders. In addition to emotional disturbances, both mood and anxiety disorders are often characterized by disruptions in normal sleep-wake cycles, a behavior that has not been well characterized in adversely-reared non-human primates. Because polysomnographic measures are difficult to obtain in unrestrained monkeys we used 24...

  20. L-theanine attenuates abstinence signs in morphine-dependent rhesus monkeys and elicits anxiolytic-like activity in mice

    OpenAIRE

    Wise, Laura E.; Premaratne, Ishani D.; Gamage, Thomas F; Lichtman, Aron H.; Hughes, Larry D.; Harris, Louis S.; Aceto, Mario D.

    2012-01-01

    L-theanine, 2-Amino-4-(ethylcarbamoyl) butyric acid, an amino acid found in green tea (Camellia sinensis), is sold in the United States as a dietary supplement to reduce stress and improve cognition and mood. The observations that L-theanine has been shown to inhibit caffeine’s stimulatory effects and that caffeine produces precipitated withdrawal signs in opioid-addicted monkeys and some opioid withdrawal signs in some normal monkeys, suggest that L-theanine may suppress opioid withdrawal si...

  1. Postnatal remodeling of the neural components of the epithelial-mesenchymal trophic unit in the proximal airways of infant rhesus monkeys exposed to ozone and allergen

    International Nuclear Information System (INIS)

    Nerves and neuroendocrine cells located within the airway epithelium are ideally situated to sample a changing airway environment, to transmit that information to the central nervous system, and to promote trophic interactions between epithelial and mesenchymal cellular and acellular components. We tested the hypothesis that the environmental stresses of ozone (O3) and house dust mite allergen (HDMA) in atopic infant rhesus monkeys alter the distribution of airway nerves. Midlevel bronchi and bronchioles from 6-month-old infant monkeys that inhaled filtered air (FA), house dust mite allergen HDMA, O3, or HDMA + O3 for 11 episodes (5 days each, 0.5 ppm O3, 8 h/day followed by 9 days recovery) were examined using immunohistochemistry for the presence of Protein gene product 9.5 (PGP 9.5), a nonspecific neural indicator, and calcitonin gene-related peptide (CGRP). Along the axial path between the sixth and the seventh intrapulmonary airway generations, there were small significant (P 3, while in monkeys exposed to HDMA + O3 there was a greater significant (P 3 or HDMA + O3 there was a significant increase in the number of PGP 9.5 positive/CGRP negative cells that were anchored to the basal lamina and emitted projections in primarily the lateral plain and often intertwined with projections and cell bodies of other similar cells. We conclude that repeated cycles of acute injury and repair associated with the episodic pattern of ozone and allergen exposure alter the normal development of neural innervation of the epithelial compartment and the appearance of a new population of undefined PGP 9.5 positive cells within the epithelium

  2. Binding kinetics of 11C-N-methyl piperidyl benzilate (11C-NMPB) in a rhesus monkey brain using the cerebellum as a reference region

    International Nuclear Information System (INIS)

    The binding kinetics of' 11C-N-methyl piperidyl benzilate (11C-NMPB) in rhesus monkey brain were studied using animal positron emission tomography (PET) (SHR2000). This study is intended to assess the validity of the method using the cerebellum as a reference region, and to evaluate the effects of anesthesia on 11C -NMPB binding. Two monkeys, anesthetized with ketamine, received intravenous 11C-NMPB alone (370-760 MBq, 11C-NMPB accumulated densely in the striatum and cerebral cortex with time. In contrast, the tracer accumulation significantly decreased with increased doses of nonradioactive NMPB. In the cerebellum, on the other hand, the accumulation of 11C-NMPB remained low and the tracer was slowly eliminated from the brain following the injection. 11C-NMPB binding in the cerebellum was barely affected by the increased dose of nonradioactive NMPB. We thus concluded that the specific 11C-NMPB binding was negligible in the cerebellum, and performed simplified evaluation of 11C-NMPB binding in each brain region by a graphical method using the cerebellum as a reference region. PET was conducted 26 times, in total both in ketamine-anesthetized and awake monkeys (n=3 each). Measurements of 11C-NMPB binding showed good run-to-run reproducibility within individual animals. When 11C-NMPB binding was compared between ketamine-treated and awake animals, a significant increase in 11C-NMPB binding was observed in the striatum but not in other brain regions of ketamine-treated animals. (author)

  3. Effects of the kappa opioid receptor antagonist nor-binaltorphimine (nor-BNI) on cocaine versus food choice and extended-access cocaine intake in rhesus monkeys.

    Science.gov (United States)

    Hutsell, Blake A; Cheng, Kejun; Rice, Kenner C; Negus, Sidney Stevens; Banks, Matthew L

    2016-03-01

    The dynorphin/kappa opioid receptor (KOR) system has been implicated as one potential neurobiological modulator of the abuse-related effects of cocaine and as a potential target for medications development. This study determined effects of the KOR antagonist nor-binaltorphimine (nor-BNI) on cocaine self-administration under a novel procedure that featured two daily components: (1) a 2-hour 'choice' component (9:00-11:00 am) when monkeys could choose between food pellets and cocaine injections (0-0.1 mg/kg per injection, intravenous) and (2) a 20-hour 'extended-access' component (noon to 8:00 am) when cocaine (0.1 mg/kg per injection) was available under a fixed-ratio schedule to promote high daily cocaine intakes. Rhesus monkeys (n = 4) were given 14 days of exposure to the choice + extended-access procedure then treated with nor-BNI (3.2 or 10.0 mg/kg, intramuscular), and cocaine choice and extended-access cocaine intake were evaluated for an additional 14 days. Consistent with previous studies, cocaine maintained both a dose-dependent increase in cocaine choice during choice components and a high level of cocaine intake during extended-access components. Neither 3.2 nor 10 mg/kg nor-BNI significantly altered cocaine choice or extended-access cocaine intake. In two additional monkeys, nor-BNI also had no effect on cocaine choice or extended-access cocaine intake when it was administered at the beginning of exposure to the extended-access components. Overall, these results do not support a major role for the dynorphin/KOR system in modulating cocaine self-administration under these conditions in non-human primates nor do they support the clinical utility of KOR antagonists as a pharmacotherapeutic strategy for cocaine addiction. PMID:25581305

  4. Toxicity and disposition of 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF) in the rhesus monkey (Macaca mulatta)

    Energy Technology Data Exchange (ETDEWEB)

    Brewster, D.W.; Elwell, M.R.; Birnbaum, L.S.

    1988-04-01

    The toxicity and disposition of 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF), a ubiquitous and acutely toxic environmental contaminant, was examined in three adult male Rhesus monkeys administered a single iv dose of 34 micrograms (0.1 mumol)/kg. Within 20 min, 4PeCDF was eliminated from the blood and was distributed to the liver, skin, adipose, and muscle tissues. Excretion occurred primarily via the feces with a minimum whole body half-life approximately 38 days. Within 7-14 days after administration, the packed cell volume and serum triglyceride and bile acid concentrations were significantly increased while serum cholesterol, protein, and albumin concentrations were decreased relative to pretreatment levels. Thyroid hormone levels were also altered with an increase in TSH and a decrease in T3 and T4 concentrations. After 28 days, two monkeys began exhibiting alopecia, hyperkeratinization of the toe and finger nails, facial chloracne-like lesions, and loss of body weight. They subsequently died 40 and 48 days after treatment. Similar symptoms of toxicity were observed in the third animal 58 days after 4PeCDF administration, but this animal appeared to fully recover and was administered 4PeCDF orally and (3H)1,2,3,7,8-pentachloro-dibenzofuran (1PeCDF) dermally 238 days after the initial iv dose. In this animal, approximately 2% of an oral dose of (14C)-4PeCDF was absorbed from the stomach and small intestine in 6 hr and was distributed mainly to the muscle and skin and less than 99% of a dermal dose of 1PeCDF remained at the site of application. Pathological findings in the monkeys that died indicated hyperplastic and metaplastic changes in the gastric mucosa, the Meibomian glands of the eyelid, and the ceruminous glands of the ear. Regression of these lesions was present in the surviving animal.

  5. Toxicity and disposition of 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF) in the rhesus monkey (Macaca mulatta)

    International Nuclear Information System (INIS)

    The toxicity and disposition of 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF), a ubiquitous and acutely toxic environmental contaminant, was examined in three adult male Rhesus monkeys administered a single iv dose of 34 micrograms (0.1 mumol)/kg. Within 20 min, 4PeCDF was eliminated from the blood and was distributed to the liver, skin, adipose, and muscle tissues. Excretion occurred primarily via the feces with a minimum whole body half-life approximately 38 days. Within 7-14 days after administration, the packed cell volume and serum triglyceride and bile acid concentrations were significantly increased while serum cholesterol, protein, and albumin concentrations were decreased relative to pretreatment levels. Thyroid hormone levels were also altered with an increase in TSH and a decrease in T3 and T4 concentrations. After 28 days, two monkeys began exhibiting alopecia, hyperkeratinization of the toe and finger nails, facial chloracne-like lesions, and loss of body weight. They subsequently died 40 and 48 days after treatment. Similar symptoms of toxicity were observed in the third animal 58 days after 4PeCDF administration, but this animal appeared to fully recover and was administered 4PeCDF orally and [3H]1,2,3,7,8-pentachloro-dibenzofuran (1PeCDF) dermally 238 days after the initial iv dose. In this animal, approximately 2% of an oral dose of [14C]-4PeCDF was absorbed from the stomach and small intestine in 6 hr and was distributed mainly to the muscle and skin and less than 99% of a dermal dose of 1PeCDF remained at the site of application. Pathological findings in the monkeys that died indicated hyperplastic and metaplastic changes in the gastric mucosa, the Meibomian glands of the eyelid, and the ceruminous glands of the ear. Regression of these lesions was present in the surviving animal

  6. Positron emission tomography in drug evaluation: Influence of three different catechol-O-methyltransferase inhibitors on metabolism of [NCA] 6-[18F]fluoro-l-dopa in Rhesus monkey

    International Nuclear Information System (INIS)

    We compared the influence of three different catechol-O-methyltransferase (COMT) inhibitors (CGP 28014, OR-611 and Ro 40-7592) on the metabolism of no-carrier-added (NCA) 6-[18F]fluoro-l-dopa (6-FDOPA) in one Rhesus monkey. All three COMT inhibitors improved 6-FDOPA availability in plasma, increased the specific uptake in the brain and thus improved 6-FDOPA uptake measurements using positron emission tomography (PET). Best results were obtained with Ro 40-7592

  7. Timing of moderate level prenatal alcohol exposure influences gene expression of sensory processing behavior in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Mary L Schneider

    2009-11-01

    Full Text Available Sensory processing disorder (SPD, characterized by over- or under-responsivity to non-noxious environmental stimuli, is a common but poorly understood disorder. We examined the role of prenatal alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR, and striatal dopamine (DA function on behavioral measures of sensory responsivity to repeated non-noxious sensory stimuli in macaque monkeys. Results indicated that early gestation alcohol exposure induced behavioral under-responsivity to environmental stimuli in monkeys carrying the short (s rh5-HTTLPR allele compared to both early-exposed monkeys homozygous for the long (l allele and monkeys from middle-to-late exposed pregnancies and controls, regardless of genotype. Moreover, prenatal timing of alcohol exposure altered the relationship between sensory scores and DA D2R availability. In early-exposed monkeys, a positive relationship was shown between sensory scores and DA D2R availability, with low or blunted DA function associated with under-responsive sensory function. The opposite pattern was found for the middle-to-late gestation alcohol-exposed group. These findings raise questions about how the timing of prenatal perturbation and genotype contributes to effects on neural processing and possibly alters neural connections.

  8. Delayed response task performance as a function of age in cynomolgus monkeys (Macaca fascicularis)

    DEFF Research Database (Denmark)

    Darusman, H S; Call, J; Sajuthi, D; Schapiro, S J; Gjedde, A; Kalliokoski, O; Hau, J

    2014-01-01

    We compared delayed response task performance in young, middle-aged, and old cynomolgus monkeys using three memory tests that have been used with non-human primates. Eighteen cynomolgus monkeys-6 young (4-9 years), 6 middle-aged (10-19 years), and 6 old (above 20 years)-were tested. In general, the...... old monkeys scored significantly worse than did the animals in the two other age groups. Longer delays between stimulus presentation and response increased the performance differences between the old and younger monkeys. The old monkeys in particular showed signs of impaired visuo-spatial memory and...

  9. Sporadic premature aging in a Japanese monkey: a primate model for progeria.

    Directory of Open Access Journals (Sweden)

    Takao Oishi

    Full Text Available In our institute, we have recently found a child Japanese monkey who is characterized by deep wrinkles of the skin and cataract of bilateral eyes. Numbers of analyses were performed to identify symptoms representing different aspects of aging. In this monkey, the cell cycle of fibroblasts at early passage was significantly extended as compared to a normal control. Moreover, both the appearance of senescent cells and the deficiency in DNA repair were observed. Also, pathological examination showed that this monkey has poikiloderma with superficial telangiectasia, and biochemical assay confirmed that levels of HbA1c and urinary hyaluronan were higher than those of other (child, adult, and aged monkey groups. Of particular interest was that our MRI analysis revealed expansion of the cerebral sulci and lateral ventricles probably due to shrinkage of the cerebral cortex and the hippocampus. In addition, the conduction velocity of a peripheral sensory but not motor nerve was lower than in adult and child monkeys, and as low as in aged monkeys. However, we could not detect any individual-unique mutations of known genes responsible for major progeroid syndromes. The present results indicate that the monkey suffers from a kind of progeria that is not necessarily typical to human progeroid syndromes.

  10. Functional recovery after rhesus monkey spinal cord injury by transplantation of bone marrow mesenchymal-stem cell-derived neurons

    Institute of Scientific and Technical Information of China (English)

    DENG Yu-bin; YUAN Qing-tao; LIU Xiao-gang; LIU Xiao-lin; LIU Yu; LIU Zu-guo; ZHANG Cheng

    2005-01-01

    Background The treatment of spinal cord injury is still a challenge. This study aimed at evaluating the therapeutical effectiveness of neurons derived form mesenchymal stem cells (MSCs) for spinal cord injury.Methods In this study, rhesus MSCs were isolated and induced by cryptotanshinone in vitro and then a process of RT-PCR was used to detect the expression of glutamic acid decarboxylase (GAD) gene. The induced MSCs were tagged with Hoechst 33342 and injected into the injury site of rhesus spinal cord made by the modified Allen method. Following that, behavior analysis was made after 1 week, 1 month, 2 months and 3 months. After 3 months, true blue chloride retrograde tracing study was also used to evaluate the re-establishment of axons pathway and the hematoxylin-eosin (HE) staining and immunohistochemistry were performed after the animals had been killed.Results In this study, the expression of mRNA of GAD gene could be found in the induced MSCs but not in primitive MSCs and immunohistochemistry could also confirm that rhesus MSCs could be induced and differentiated into neurons. Behavior analysis showed that the experimental animals restored the function of spinal cord up to grade 2-3 of Tarlov classification. Retrograde tracing study showed that true blue chollide could be found in the rostral thoracic spinal cords, red nucleus and sensory-motor cortex.Conclusions These results suggest that the transplantation is safe and effective.

  11. Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) in rats and rhesus monkeys: Effect of anatomical site

    International Nuclear Information System (INIS)

    Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) was determined in rats and rhesus monkeys. Lindane is in widespread use as a 1% cream or lotion scabicide formulation and as a 1% miticide shampoo for body lice control in humans. Results obtained following our in vivo dermal absorption procedure demonstrated that 18 +/- 4.1%, 34 +/- 5.2%, and 54 +/- 26.3% of the applied dose was absorbed following topical applications at a rate of 1.5 micrograms/cm2 (6.2 micrograms/100 microliters of acetone) of the 14C-labeled pesticide to 4.2-cm2 regions of the forearm (n = 8), forehead (n = 7), and palm (n = 4) of rhesus monkeys, respectively. Dose sites were washed with soapy water 24 h posttreatment. Comparative studies in rats (n = 5) dosed middorsally demonstrated 31 +/- 9.5% absorption. Statistical analysis of the 14C excretion kinetics demonstrated slower clearance of lindane from rats than monkey forearm, forehead, or palm. Intramuscular (im) injections of 14C-lindane gave 52 +/- 7.1% recovery in monkey (n = 8) and 64 +/- 5.9% in rats (n = 5), suggesting body storage of this lipophilic chemical

  12. Apparent affinity estimates of rimonabant in combination with anandamide and chemical analogs of anandamide in rhesus monkeys discriminating Δ9-tetrahydrocannabinol

    Science.gov (United States)

    2016-01-01

    Rationale Anandamide and Δ9-tetrahydrocannabinol (Δ9-THC) sometimes produce different discriminative stimulus effects and, therefore, appear to differ in their mechanism of action. In order to understand the widespread use of cannabis and the therapeutic potential of cannabinoids, mechanisms responsible for behavioral effects need to be identified. Objective Drug discrimination was used to compare the mechanism of action of Δ9-THC, anandamide, and two structural analogs of anandamide in rhesus monkeys. Materials and methods Monkeys discriminated Δ9-THC (0.1 mg/kg i.v.) from vehicle. Δ9-THC, anandamide, methanandamide, and arachidonylcyclopropylamide (ACPA) were administered i.v. alone and in combination with at least one dose of rimonabant. Schild analysis and single-dose apparent affinity estimates were used to estimate the potency of rimonabant as an antagonist of each cannabinoid; these values were compared to examine whether the same receptors mediated discriminative stimulus effects. Results Δ9-THC, ACPA, methanandamide, and anandamide produced greater than 96% of responses on the Δ9-THC lever. The ED50 values were 0.024 mg/kg for Δ9-THC, 0.14 mg/kg for ACPA, 0.28 mg/kg for methanandamide, and 1.7 mg/kg for anandamide. The duration of action of Δ9-THC was 4–6 h and longer than the duration of action ACPA, methanandamide, and anandamide (i.e., each less than 50 min). Rimonabant surmountably antagonized the discriminative stimulus effects of each agonist, and the apparent affinity estimates (pA2 and pKB values) were 6.24–6.83. Conclusions Rimonabant can produce surmountable antagonism of the behavioral effects of not only Δ9-THC but also anandamide, methanandamide, and ACPA, and the interactions appear simple, competitive, and reversible. These cannabinoid agonists act at the same receptors to produce discriminative stimulus effects. PMID:18592221

  13. In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects tooth development in rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Iku; Kazuhiro, Tsuga; Yasumasa, Akagawa [Hiroshima Univ. (Japan); Mineo, Yasuda; Hiroshi, Sumida [Hiroshima International Univ. (Japan); Akihiro, Arima; Toshio, Ihara [Shin Nippon Biomedical Laboratories, Ltd., Kagoshima (Japan); Shunichiro, Kubota [Tokyo Univ. (Japan); Kazuo, Asaoka [Kyoto Univ., Inuyama (Japan). Primate Research Institute; Takumi, Takasuga [Shimadzu Techno-Research Inc., Kyoto (Japan)

    2004-09-15

    The current tolerable daily intake (TDI) of dioxin and dioxin related compounds has been set at 4 pg TEQ/kg/day in Japan. This value was calculated from the lowest-observed-adverse-effect level (LOAEL) in experimental animals, mostly rodents. Gray et al. reported that a single oral dose of 200 ng/kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to pregnant rats on day 15 of gestation resulted in abnormalities of reproductive organs in the offspring. The maternal body burden at this dose was measured to be 86 ng/kg. To attain this body burden level, human daily intake was calculated to be 43.6 pg/kg/day. An uncertainty factor of 10 was applied to this value, and the human TDI was established. However, due to great differences in the biological half life of TCDD between human and rodents, the validity of this calculation is questioned. To obtain more reliable LOAEL in the second generation, we initiated a long-term study in rhesus monkeys in 1999. In rodents, teeth are known to be targets of developmental toxicity of dioxin. In utero and lactational TCDD exposure affects rat incisor and molar development. In humans also tooth abnormalities were reported among populations exposed to dioxins. In our monkey experiment, some young were stillborn or died neonatally. These animals provided us with a unique opportunity to study tooth development in primate young exposed to TCDD in utero and lactationally. By macroscopic observation we found some tooth abnormalities among died young exposed to TCDD5. This prompted us to examine surviving young by radiography. This is an interim report of our findings in these young.

  14. Pharmacokinetics and Brain Uptake in the Rhesus Monkey of a Fusion Protein of Arylsulfatase A and a Monoclonal Antibody Against the Human Insulin Receptor

    Science.gov (United States)

    Boado, Ruben J.; Lu, Jeff Zhiqiang; Hui, Eric K.-W.; Sumbria, Rachita K.; Pardridge, William M.

    2014-01-01

    Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder of the brain caused by mutations in the gene encoding the lysosomal sulfatase, arylsulfatase A (ASA). It is not possible to treat the brain in MLD with recombinant ASA, because the enzyme does not cross the blood-brain barrier (BBB). In the present investigation, a BBB-penetrating IgG-ASA fusion protein is engineered and expressed, where the ASA monomer is fused to the carboxyl terminus of each heavy chain of an engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb crosses the BBB via receptor-mediated transport on the endogenous BBB insulin receptor, and acts as a molecular Trojan horse to ferry the ASA into brain from blood. The HIRMAb-ASA is expressed in stably transfected Chinese hamster ovary cells grown in serum free medium, and purified by protein A affinity chromatography. The fusion protein retains high affinity binding to the HIR, EC50 = 0.34 ± 0.11 nM, and retains high ASA enzyme activity, 20 ± 1 units/mg. The HIRMAb-ASA fusion protein is endocytosed and triaged to the lysosomal compartment in MLD fibroblasts. The fusion protein was radio-labeled with the Bolton-Hunter reagent, and the [125I]-HIRMAb-ASA rapidly penetrates the brain in the Rhesus monkey following intravenous administration. Film and emulsion autoradiography of primate brain shows global distribution of the fusion protein throughout the monkey brain. These studies describe a new biological entity that is designed to treat the brain of humans with MLD following non-invasive, intravenous infusion of an IgG-ASA fusion protein. PMID:23192358

  15. Regional distribution of the opioid receptor agonist N-(methyl- sup 11 C)pethidine in the brain of the rhesus monkey studied with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Hartvig, P. (Hospital Pharmacy, University Hospital, Uppsala (Sweden)); Eckernaes, S.Aa. (Departments of Neurology, University Hospital, Uppsala (Sweden)); Lindberg, B.S. (Department of Obstetrics and Gynaelogy, University Hospital, Uppsala (Sweden)); Lundqvist, H. (Centre for Radiation Sciences, University of Uppsala (Sweden)); Antoni, G.; Rimland, A.; Laangstroem, B. (Department of Organic Chemistry, University of Uppsala (Sweden))

    1990-01-01

    The regional distribution and kinetics in the brain of Rhesus monkeys of N-(methyl-{sup 11}C)-pethidine have been studied by positron emission tomography, PET. {sup 11}C-Pethidine reached the brain with peak radioactivities appearing within 6-10 min. after administration. Highest radioactivities were measured in areas corresponding to the thalamus, the striatal area and also the lowest transection of the temporal lobes, with an uptake of 2.7-3.1 times the homogenous dilution of the radioactive dose. Low radioactivities were seen in the cerebellum and the occipital lobes. This distribution corresponds to the regional density of opioid receptors using in vitro binding techniques. The {sup 11}C-pethidine derived radioactivity left the brain with an initial half-life of 40--60 minutes, followed by an elimination which paralleled the plasma elimination of unlabelled pethidine. After pretreatment of the monkey with a small dose of naloxone, the radioactivities decreased about 40% in areas corresponding to the thalamus, striatum and lowest section of the temporal lobes, indicating competition for the same binding sties. By the use of a three-compartment model, it was possible to get an estimate of {sup 11}C-pethidine receptor binding characteristics in the brain. The ratio of Kon/Koff, equal to Bmax.Kd, was 0.06-0.1. This indicates that pethidine is bound with low affinity to the opioid receptors and is a poor ligand for studies of opioid receptor function with PET. Brain kinetics of {sup 11}C-pethidine is mainly determined by its blood kinetics. (author).

  16. Regional distribution of the opioid receptor agonist N-(methyl-11C)pethidine in the brain of the rhesus monkey studied with positron emission tomography

    International Nuclear Information System (INIS)

    The regional distribution and kinetics in the brain of Rhesus monkeys of N-(methyl-11C)-pethidine have been studied by positron emission tomography, PET. 11C-Pethidine reached the brain with peak radioactivities appearing within 6-10 min. after administration. Highest radioactivities were measured in areas corresponding to the thalamus, the striatal area and also the lowest transection of the temporal lobes, with an uptake of 2.7-3.1 times the homogenous dilution of the radioactive dose. Low radioactivities were seen in the cerebellum and the occipital lobes. This distribution corresponds to the regional density of opioid receptors using in vitro binding techniques. The 11C-pethidine derived radioactivity left the brain with an initial half-life of 40-60 min., followed by an elimination which paralleled the plasma elimination of unlabelled pethidine. After pretreatment of the monkey with a small dose of naloxone, the radioactivities decreased about 40% in areas corresponding to the thalamus, striatum and lowest section of the temporal lobes, indicating competition for the same binding sties. By the use of a three-compartment model, it was possible to get an estimate of 11C-pethidine receptor binding characteristics in the brain. The ratio of Kon/Koff, equal to Bmax.(Kd, was 0.06-0.1. This indicates that pethidine is bound with low affinity to the opioid receptors and is a poor ligand for studies of opioid receptor function with PET. Brain kinetics of 11C-pethidine is mainly determined by its blood kinetics. (author)

  17. Interleukin-8 and interleukin-10, brain volume and microstructure, and the influence of calorie restriction in old rhesus macaques

    OpenAIRE

    Willette, A.A.; Coe, C. L.; Birdsill, A. C.; Bendlin, B. B.; Colman, R.J.; Alexander, A.L.; Allison, D B; Weindruch, R.H.; Johnson, S.C.

    2013-01-01

    Higher systemic levels of the proinflammatory cytokine interleukin-6 (IL-6) were found to be associated with lower gray matter volume and tissue density in old rhesus macaques. This association between IL-6, and these brain indices were attenuated by long-term 30 % calorie restriction (CR). To extend these findings, the current analysis determined if a CR diet in 27 aged rhesus monkeys compared to 17 normally fed controls reduced circulating levels of another proinflammatory cytokine, interle...

  18. The utility of rhesus monkey (Macaca mulatta and other non-human primate models for preclinical testing of Leishmania candidate vaccines

    Directory of Open Access Journals (Sweden)

    Gabriel Grimaldi Jr

    2008-11-01

    Full Text Available Leishmaniasis causes significant morbidity and mortality, constituting an important global health problem for which there are few effective drugs. Given the urgent need to identify a safe and effective Leishmania vaccine to help prevent the two million new cases of human leishmaniasis worldwide each year, all reasonable efforts to achieve this goal should be made. This includes the use of animal models that are as close to leishmanial infection in humans as is practical and feasible. Old world monkey species (macaques, baboons, mandrills etc. have the closest evolutionary relatedness to humans among the approachable animal models. The Asian rhesus macaques (Macaca mulatta are quite susceptible to leishmanial infection, develop a human-like disease, exhibit antibodies to Leishmania and parasite-specific T-cell mediated immune responses both in vivo and in vitro, and can be protected effectively by vaccination. Results from macaque vaccine studies could also prove useful in guiding the design of human vaccine trials. This review summarizes our current knowledge on this topic and proposes potential approaches that may result in the more effective use of the macaque model to maximize its potential to help the development of an effective vaccine for human leishmaniasis.

  19. Saccade generation by the frontal eye fields in rhesus monkeys is separable from visual detection and bottom-up attention shift.

    Directory of Open Access Journals (Sweden)

    Kyoung-Min Lee

    Full Text Available The frontal eye fields (FEF, originally identified as an oculomotor cortex, have also been implicated in perceptual functions, such as constructing a visual saliency map and shifting visual attention. Further dissecting the area's role in the transformation from visual input to oculomotor command has been difficult because of spatial confounding between stimuli and responses and consequently between intermediate cognitive processes, such as attention shift and saccade preparation. Here we developed two tasks in which the visual stimulus and the saccade response were dissociated in space (the extended memory-guided saccade task, and bottom-up attention shift and saccade target selection were independent (the four-alternative delayed saccade task. Reversible inactivation of the FEF in rhesus monkeys disrupted, as expected, contralateral memory-guided saccades, but visual detection was demonstrated to be intact at the same field. Moreover, saccade behavior was impaired when a bottom-up shift of attention was not a prerequisite for saccade target selection, indicating that the inactivation effect was independent of the previously reported dysfunctions in bottom-up attention control. These findings underscore the motor aspect of the area's functions, especially in situations where saccades are generated by internal cognitive processes, including visual short-term memory and long-term associative memory.

  20. Synthesis of some 11C-labelled MAO-A inhibitors and their in vivo uptake kinetics in rhesus monkey brain

    International Nuclear Information System (INIS)

    Five potential MAO-A inhibitors--harmine, N-methyl-harmine, harmaline, brofaromine, and clorgyline--were labelled with 11C and their brain kinetics evaluated in vivo in rhesus monkey using PET. The compounds were synthesized by alkylation with 11C methyl iodide and obtained in 48-89% radiochemical yield within 40 to 45 min synthesis time and with specific radioactivities in the region of 0.49-2.4 Ci μmol-1 (18-87 GBq μmol-1) at the end of synthesis. The kinetic pattern after administration of MAO-A inhibitors was comparable to that seen in the tracer study when using 11C-brofaromine, 11C-harmaline, or 11C-clorgyline, although the magnitude of uptake markedly increased in the case of brofaromine and harmaline. Both 11C-methylharmine and 11C-harmine showed a significant washout in the inhibition studies. The kinetics of brain uptake with and without MAO-A inhibition is compatible with a significant fraction of the tracer bound to MAO-A for 11C-methylharmine and 11C-harmine, whereas 11C-brofaromine, 11C-harmaline, or 11C-clorgyline did not seem to show specific enzyme binding

  1. The impact of early immune destruction on the kinetics of postacute viral replication in rhesus monkey infected with the simian-human immunodeficiency virus 89.6P

    International Nuclear Information System (INIS)

    Set-point viral load is positively correlated with the extent of initial viral replication in pathogenic simian-human immunodeficiency virus (SHIV) infection. To elucidate the mechanisms underlying the correlation, we conducted a systematic investigation in rhesus monkeys infected with the highly pathogenic SHIV 89.6P. This model is widely used in the preclinical evaluation of AIDS vaccine candidates and a thorough understanding of the model's biology is important to the proper interpretation of these evaluations. We found that the levels of peak viremia were positively correlated not only with the levels of set-point viremia but, importantly, with the extent of initial overall immune destruction as indicated by the degree of CD4+ T cell depletion and lymph node germinal center (GC) formation. The extent of initial overall immune destruction was inversely correlated with subsequent development and maintenance of virus-specific cellular and humoral immune responses. Thus, these data suggest that the extent of early immune damage determines the development and durability of virus-specific immunity, thereby playing a critical role in establishing the levels of set-point viral replication in SHIV infection. Vaccines that limit both the initial viral replication and the extent of early immune damage will therefore mediate long-term virus replication control and mitigation of long-term immune destruction in this model of immunodeficiency virus infection

  2. Saturated norepinephrine transporter occupancy by atomoxetine relevant to clinical doses: a rhesus monkey study with (S,S)-[{sup 18}F]FMeNER-D{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Takano, Akihiro; Gulyas, Balazs; Varrone, Andrea; Halldin, Christer [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm (Sweden); Maguire, Ralph Paul [Pfizer Global Research and Development, New London, CT (United States); Novartis Institutes for BioMedical Research, Basel (Switzerland)

    2009-08-15

    In a previous PET study on norepinephrine transporter (NET) occupancy in the nonhuman primate brain, the relationship between NET occupancy and atomoxetine plasma concentration, and occupancies among different brain regions, were not demonstrated adequately. It may therefore be difficult to translate the results to the clinical situations. In the present study, the detailed change of NET occupancy was investigated among a wider range of doses in a more advanced manner. Two rhesus monkeys were examined using a high-resolution PET system with (S,S)-[{sup 18}F]FMeNER-D{sub 2} under baseline conditions and after steady-state infusion of different doses of atomoxetine (0.003 to 0.12 mg/kg per hour). NET occupancy of the thalamus, brainstem and anterior cingulate cortex was calculated using BP{sub ND} obtained with the simplified reference tissue model. NET occupancy increased regionally and uniformly as the plasma concentration of atomoxetine increased. The estimated Kd value (the amount to occupy 50% of NET) in the thalamus was 16 ng/ml. The results indicate that clinical doses of atomoxetine would occupy NET almost completely. (orig.)

  3. Retention, distribution, and excretion of 239PuO2 particles labeled with 169Yb in the Rhesus monkey after a single acute inhalation exposure

    International Nuclear Information System (INIS)

    Sixteen Rhesus monkeys were exposed to a high fired 239PuO2 aerosol labeled with 169Yb, and retention, distribution, and excretion patterns were determined. After an early rapid clearance phase, which had a half-life of less than one day, the remaining plutonium was retained in the lungs with a half-life that appeared to be greater than 500 days. By 30 days after exposure, 99 percent of the 239Pu in the body was in the lungs. At this time, 6 to 10 percent of the 169Yb burden was in the carcass and skeleton suggesting that there was dissociation of some 169Yb from the particles. The remaining 169Yb activity was in the lungs. There was little 239Pu in the liver, bone, or lymph nodes. The particulate material was cleared rapidly from the gastrointestinal and upper respiratory tracts and appeared in feces over the first four days. The level of 239Pu in feces returned to background by six days. Urinary excretion of 239Pu reached a peak by 8 to 10 days and then remained at a constant rate throughout the remainder of the experiment. These data are useful in calculating radiation dose to a variety of organs and relating this dose to the appearance of late effects from inhaled alpha-emitting particles. (U.S.)

  4. Saturated norepinephrine transporter occupancy by atomoxetine relevant to clinical doses: a rhesus monkey study with (S,S)-[18F]FMeNER-D2

    International Nuclear Information System (INIS)

    In a previous PET study on norepinephrine transporter (NET) occupancy in the nonhuman primate brain, the relationship between NET occupancy and atomoxetine plasma concentration, and occupancies among different brain regions, were not demonstrated adequately. It may therefore be difficult to translate the results to the clinical situations. In the present study, the detailed change of NET occupancy was investigated among a wider range of doses in a more advanced manner. Two rhesus monkeys were examined using a high-resolution PET system with (S,S)-[18F]FMeNER-D2 under baseline conditions and after steady-state infusion of different doses of atomoxetine (0.003 to 0.12 mg/kg per hour). NET occupancy of the thalamus, brainstem and anterior cingulate cortex was calculated using BPND obtained with the simplified reference tissue model. NET occupancy increased regionally and uniformly as the plasma concentration of atomoxetine increased. The estimated Kd value (the amount to occupy 50% of NET) in the thalamus was 16 ng/ml. The results indicate that clinical doses of atomoxetine would occupy NET almost completely. (orig.)

  5. Distribution and kinetics of 3-O-methyl-6-[18F]fluoro-L-dopa in the rhesus monkey brain

    International Nuclear Information System (INIS)

    Most attempts to model accurately [18F]-DOPA imaging of the dopamine system are based on the assumptions that its main peripheral metabolite, 3-O-methyl-6-[18F]fluoro-L-DOPA ([18F]3-OM-DOPA), crosses the blood-brain barrier but is present as a homogenous distribution throughout the brain, in part because it is not converted into [18F]DOPA in significant quantities. These assumptions were based mainly on data in rodents. Little information is available in the primate. To verify the accuracy of the above assumptions, the authors administered 18F-labeled 3-OM-DOPA to normal rhesus monkeys and animals with lesions of the DA nigrostriatal system. No selective 18F regional accumulation in brain was apparent in normal or lesioned animals. The plasma metabolite analysis revealed that only the negatively charged metabolites (e.g., sulfated conjugates) that do not cross the blood-brain barrier were found in significant quantities in the plasma. A one-compartment, three-parameter model was adequate to describe the kinetics of [18F]3-OM-DOPA. In conclusion, assumptions concerning [18F]3-OM-DOPA's behavior in brain appear acceptable for [18F]DOPA modeling purposes

  6. Dose-dependent effects of isoflurane on regional activity and neural network function: A resting-state fMRI study of 14 rhesus monkeys: An observational study.

    Science.gov (United States)

    Lv, Peilin; Xiao, Yuan; Liu, Bin; Wang, Yuqing; Zhang, Xiang; Sun, Huaiqiang; Li, Fei; Yao, Li; Zhang, Wenjing; Liu, Lu; Gao, Xin; Wu, Min; Tang, Yingying; Chen, Qin; Gong, Qiyong; Lui, Su

    2016-01-12

    The dose-dependent effect of isoflurane on cerebral regional activity and functional connectivity (FC) in 14 rhesus monkeys was investigated using resting-state functional MRI. Amplitude of low-frequency fluctuations (ALFF) decreased in the cerebellum, visual cortex, and cortico-subcortical network when the isoflurane dose changed from 1.0 to 1.3 MAC. ALFF decreased in the arousal system, cerebellum, sensory, visual areas, cortico-subcortical network and default mode network and increased in the bilateral dorsal prefrontal cortices, frontal eye fields and motor-related areas from 1.0 to 1.6 MAC. FC of the default mode network, frontal-parietal, cortico-subcortical, motor, sensory, auditory and visual areas was reduced when isoflurane increased from 1.0 to 1.3 MAC. FC decreased in more widespread areas, especially in regions of cortico-subcortical networks and limbic systems, when isoflurane further increased from 1.0 to 1.6 MAC. Both dose-dependent decreased and increased ALFF were separately observed, while FC deteriorated as the anesthesia deepened. These results suggest that changes continue to occur past the loss of consciousness, and the dose-dependent effects of isoflurane are different with regard to regional function and neural network integration. PMID:26633103

  7. Immune correlates of aging in outdoor-housed captive rhesus macaques (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Didier Elizabeth S

    2012-11-01

    Full Text Available Abstract Background Questions remain about whether inflammation is a cause, consequence, or coincidence of aging. The purpose of this study was to define baseline immunological characteristics from blood to develop a model in rhesus macaques that could be used to address the relationship between inflammation and aging. Hematology, flow cytometry, clinical chemistry, and multiplex cytokine/chemokine analyses were performed on a group of 101 outdoor-housed captive rhesus macaques ranging from 2 to 24 years of age, approximately equivalent to 8 to 77 years of age in humans. Results These results extend earlier reports correlating changes in lymphocyte subpopulations and cytokines/chemokines with increasing age. There were significant declines in numbers of white blood cells (WBC overall, as well as lymphocytes, monocytes, and polymorphonuclear cells with increasing age. Among lymphocytes, there were no significant declines in NK cells and T cells, whereas B cell numbers exhibited significant declines with age. Within the T cell populations, there were significant declines in numbers of CD4+ naïve T cells and CD8+ naïve T cells. Conversely, numbers of CD4+CD8+ effector memory and CD8+effector memory T cells increased with age. New multiplex analyses revealed that concentrations of a panel of ten circulating cytokines/chemokines, IFNγ, IL1b, IL6, IL12, IL15, TNFα, MCP1, MIP1α, IL1ra, and IL4, each significantly correlated with age and also exhibited concordant pairwise correlations with every other factor within this group. To also control for outlier values, mean rank values of each of these cytokine concentrations in relation to age of each animal and these also correlated with age. Conclusions A panel of ten cytokines/chemokines were identified that correlated with aging and also with each other. This will permit selection of animals exhibiting relatively higher and lower inflammation status as a model to test mechanisms of inflammation

  8. Individual differences in scanpaths correspond with serotonin transporter genotype and behavioral phenotype in rhesus monkeys (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Robert R Gibboni

    2009-11-01

    Full Text Available Scanpaths (the succession of fixations and saccades during spontaneous viewing contain information about the image but also about the viewer. To determine the viewer-dependent factors in the scanpaths of monkeys, we trained three adult males (Macaca mulatta to look for 3 s at images of conspecific facial expressions with either direct or averted gaze. The subjects showed significant differences on four basic scanpath parameters (number of fixations, fixation duration, saccade length, and total scanpath length when viewing the same facial expression/gaze direction combinations. Furthermore, we found differences between monkeys in feature preference and in the temporal order in which features were visited on different facial expressions. Overall, the between-subject variability was larger than the within- subject variability, suggesting that scanpaths reflect individual preferences in allocating visual attention to various features in aggressive, neutral, and appeasing facial expressions. Individual scanpath characteristics were brought into register with the genotype for the serotonin transporter regulatory gene (5-HTTLPR and with behavioral characteristics such as expression of anticipatory anxiety and impulsiveness/hesitation in approaching food in the presence of a potentially dangerous object.

  9. Reduced information transmission in the internal segment of the globus pallidus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced rhesus monkey models of Parkinson's disease☆

    OpenAIRE

    He, Yan; Wang, Jue; Gao, Guodong; Zhang, GuangJun

    2012-01-01

    Rhesus monkey models of Parkinson’s disease were induced by injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neural firings were recorded using microelectrodes placed in the internal segment of the globus pallidus. The wavelets and power spectra show gradual power reduction during the disease process along with increased firing rates in the Parkinson’s disease state. Singular values of coefficients decreased considerably during tremor-related activity as well as in the Parkinson’s d...

  10. Age-dependent changes in innate immune phenotype and function in rhesus macaques (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Mark Asquith

    2012-06-01

    Full Text Available Aged individuals are more susceptible to infections due to a general decline in immune function broadly referred to as immune senescence. While age-related changes in the adaptive immune system are well documented, aging of the innate immune system remains less well understood, particularly in nonhuman primates. A more robust understanding of age-related changes in innate immune function would provide mechanistic insight into the increased susceptibility of the elderly to infection. Rhesus macaques have proved a critical translational model for aging research, and present a unique opportunity to dissect age-dependent modulation of the innate immune system. We examined age-related changes in: (i innate immune cell frequencies; (ii expression of pattern recognition receptors (PRRs and innate signaling molecules; (iii cytokine responses of monocytes and dendritic cells (DC following stimulation with PRR agonists; and (iv plasma cytokine levels in this model. We found marked changes in both the phenotype and function of innate immune cells. This included an age-associated increased frequency of myeloid DC (mDC. Moreover, we found toll-like receptor (TLR agonists lipopolysaccharide (TLR4, fibroblast stimulating ligand-1 (TLR2/6, and ODN2006 (TLR7/9 induced reduced cytokine responses in aged mDC. Interestingly, with the exception of the monocyte-derived TNFα response to LPS, which increased with age, TNFα, IL-6, and IFNα responses declined with age. We also found that TLR4, TLR5, and innate negative regulator, sterile alpha and TIR motif containing protein (SARM, were all expressed at lower levels in young animals. By contrast, absent in melanoma 2 and retinoic acid-inducible gene I expression was lowest in aged animals. Together, these observations indicate that several parameters of innate immunity are significantly modulated by age and contribute to differential immune function in aged macaques.

  11. Age-dependent changes in innate immune phenotype and function in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Asquith, Mark; Haberthur, Kristen; Brown, Monica; Engelmann, Flora; Murphy, Ashleigh; Al-Mahdi, Zainab; Messaoudi, Ilhem

    2012-01-01

    Aged individuals are more susceptible to infections due to a general decline in immune function broadly referred to as immune senescence. While age-related changes in the adaptive immune system are well documented, aging of the innate immune system remains less well understood, particularly in nonhuman primates. A more robust understanding of age-related changes in innate immune function would provide mechanistic insight into the increased susceptibility of the elderly to infection. Rhesus macaques have proved a critical translational model for aging research, and present a unique opportunity to dissect age-dependent modulation of the innate immune system. We examined age-related changes in: (i) innate immune cell frequencies; (ii) expression of pattern recognition receptors (PRRs) and innate signaling molecules; (iii) cytokine responses of monocytes and dendritic cells (DC) following stimulation with PRR agonists; and (iv) plasma cytokine levels in this model. We found marked changes in both the phenotype and function of innate immune cells. This included an age-associated increased frequency of myeloid DC (mDC). Moreover, we found toll-like receptor (TLR) agonists lipopolysaccharide (TLR4), fibroblast stimulating ligand-1 (TLR2/6), and ODN2006 (TLR7/9) induced reduced cytokine responses in aged mDC. Interestingly, with the exception of the monocyte-derived TNFα response to LPS, which increased with age, TNFα, IL-6, and IFNα responses declined with age. We also found that TLR4, TLR5, and innate negative regulator, sterile alpha and TIR motif containing protein (SARM), were all expressed at lower levels in young animals. By contrast, absent in melanoma 2 and retinoic acid-inducible gene I expression was lowest in aged animals. Together, these observations indicate that several parameters of innate immunity are significantly modulated by age and contribute to differential immune function in aged macaques. PMID:22953039

  12. TPH2 5'- and 3'-regulatory polymorphisms are differentially associated with HPA axis function and self-injurious behavior in rhesus monkeys.

    Science.gov (United States)

    Chen, G-L; Novak, M A; Meyer, J S; Kelly, B J; Vallender, E J; Miller, G M

    2010-04-01

    Tryptophan hydroxylase-2 (TPH2) synthesizes neuronal serotonin and is linked to numerous behavioral traits. We have previously characterized the functionality of polymorphisms (especially 2051A>C) in 3'-untranslated region (3'-UTR) of rhesus monkey TPH2 (rhTPH2). This study further assessed the functionality of additional polymorphisms (-1605T>C, -1491Tn, -1485(AT)n, -1454A>G, -1325In>Del and -363T>G) in rhTPH2 5'-flanking region (5'-FR), and evaluated the effects of rhTPH2 5' and 3' genotypes on central serotonin turnover, hypothalamic-pituitary-adrenal (HPA) axis function and self-injurious behavior (SIB) in 32 unrelated adult male monkeys of Indian origin. Haplotypes of the rhTPH2 5'-FR polymorphisms exert a significant, cell-dependent effect on reporter gene expression, primarily conferred by -1485(AT)n. The -1485(AT)n and 2051A>C polymorphisms interact to influence cerebrospinal fluid (CSF) 5-HIAA and plasma adrenocorticotropic hormone (ACTH) in the afternoon. While -1485(AT)n exerts significant main effects on the afternoon cortisol level and nocturnal HPA negative feedback, 2051A>C has significant main effects on the morning cortisol level and cortisol response to ACTH challenge, as well as marginally significant main effects on the daytime HPA negative feedback and self-biting rate. In addition, the genotype/allele frequency of the 5'-FR -1325Ins>Del differed significantly between the self-wounders and non-wounders, whereas 3'-UTR 2128S>L polymorphism differed significantly in genotype/allele frequency between the high- and low-frequency biters. This study shows the functionality of rhTPH2 5'-FR polymorphisms, and provides evidence for the differential association of rhTPH2 5'-FR and 3'-UTR polymorphisms with HPA axis function and SIB. Our findings shed light on the role of TPH2 gene variance in physiology and behavioral traits, and also contribute to the understanding of the pathophysiology and genetics of SIB. PMID:20059554

  13. Experiment K-7-30: Effects of Spaceflight in the Cosmos Biosatellite 2044 on the Vestibular-Ocular Reflex (VOR) of Rhesus Monkeys

    Science.gov (United States)

    Cohen, B.; Cohen, N.; Helwig, D.; Solomon, D.; Kozlovskaya, I.; Sirota, M.; Yakushin, S.; Raphan, T.

    1994-01-01

    This technical paper discusses the following: (1) The VOR of two rhesus monkeys was studied before and after 14 days of spaceflight to determine effects of microgravity on the VOR. Horizontal, vertical and roll eye movements were recorded in these and six other monkeys implanted with scleral search coils. Animals were rotated about a vertical axis to determine the gain of the horizontal, vertical and roll VOR. They were rotated about axes tilted from the vertical (off-vertical axis rotation, OVAR) to determine steady state gains and effects of gravity on modulations in eye position and eye velocity. They were also tested for tilt dumping of post-rotatory nystagmus. (2) The gain of the horizontal VOR was close to unity when animals were tested 15 and 18 hours after flight. VOR gain values were similar to those registered before flight. If the gain of the horizontal VOR changes in microgravity, it must revert to normal soon after landing. (3) Steady state velocities of nystagmus induced by off-vertical axis rotation (OVAR) were unchanged by adaptation to microgravity, and the phase of the modulations was similar before and after flight. However, modulations in horizontal eye velocity had more variation after landing and were on mean about 50% larger for angles of tilt of the axis of rotation between 50 and 90?/s after flight. This difference was similar in both animals and was significant. (4) A striking finding was that tilt dumping was lost in the one animal tested for this function. This loss persisted for several days after return. This is reminiscent of the loss of response to pitch while rotating in the M-131 experiments of Skylab, and must be studied in detail in future spaceflights. (5) Thus, two major findings emerged from these studies: after spaceflight the modulation of horizontal eye velocity was larger during OVAR, and one animal lost its ability to tilt-dump its nystagmus. Both findings are consistent with the postulate that adaptation to microgravity

  14. Effects of Long-Term Odanacatib Treatment on Bone Gene Expression in Ovariectomized Adult Rhesus Monkeys: Differentiation From Alendronate.

    Science.gov (United States)

    Muise, Eric S; Podtelezhnikov, Alexei A; Pickarski, Maureen; Loboda, Andrey; Tan, Yejun; Hu, Guanghui; Thomspon, John R; Duong, Le T

    2016-04-01

    Similar efficacy of the cathepsin K inhibitor odanacatib (ODN) and the bisphosphonate alendronate (ALN) in reducing bone turnover markers and increasing bone mineral density in spine and hip were previously demonstrated in ovariectomized (OVX)-monkeys treated for 20 months in prevention mode. Here, we profiled RNA from tibial metaphysis and diaphysis of the same study using Affymetrix microarrays, and selected 204 probe sets (p < 0.001, three-group ANOVA) that were differentially regulated by ODN or ALN versus vehicle. Both drugs produced strikingly different effects on known bone-related genes and pathways at the transcriptional level. Although ALN either reduced or had neutral effects on bone resorption-related genes, ODN significantly increased the expression of osteoclast genes (eg, APC5, TNFRSF11A, CTSK, ITGB3, and CALCR), consistent with previous findings on the effects of this agent in enhancing the number of nonresorbing osteoclasts. Conversely, ALN reduced the expression of known bone formation-related genes (eg, TGFBR1, SPP1, RUNX2, and PTH1R), whereas ODN either increased or had neutral effects on their expression. These differential effects of ODN versus ALN on bone resorption and formation were highly correlative to the changes in bone turnover markers, cathepsin K (Catk) target engagement marker serum C-terminal cross-linked telopeptide (1-CTP) and osteoclast marker tartrate resistant acid phosphatase isoform 5b (TRAP5b) in the same monkeys. Overall, the molecular profiling results are consistent with the known pharmacological actions of these agents on bone remodeling and clearly differentiate the molecular mechanisms of ODN from the bisphosphonates. © 2016 American Society for Bone and Mineral Research. PMID:26587671

  15. Localization and distribution of tissue type and urokinase type plasminogen activators and their inhibitors Type 1 and 2 in human and rhesus monkey fetal membranes.

    Science.gov (United States)

    Liu, Y X; Hu, Z Y; Liu, K; Byrne, S; Zou, R J; Ny, T; d'Lacey, C; Ockleford, C D

    1998-01-01

    Fetal membranes consist of 10 distinct layers including components of amnion, chorion and decidua, the latter being of maternal origin. They form mechanically integrated sheets capable of retaining amniotic fluid and play an essential role in protecting fetal growth and development in the pregnant uterus. The extracellular matrix, substrate for plasminogen activators (PAs), is an important supportive framework of the fetal membranes. Fetal membranes from women with preterm premature rupture of membranes may differ in their protease activity compared with normal membranes. To identify the presence of PAs and their inhibitors (PAI) and their possible role in the process of fetal membrane rupture, this study investigated the distribution and localization of both protein and mRNA for tissue (t) and urokinase (u) PA and their inhibitors type 1 (PAI-1) and type 2 (PAI-2) in amniochorion of human and rhesus monkey using conventional and confocal immunofluorescence microscopy. In situ hybridization analysis showed that the distribution and localization of mRNAs for tPA, uPA, PAI-1 and PAI-2 were similar in the fetal membranes of human and rhesus monkey; no obvious species difference was observed. Evidence of tPA mRNA was detected in amniotic epithelium, trophoblast cells and nearly all cells of the decidual layer. Strong expression of uPA mRNA was noted in the decidual cells which increased in intensity as the abscission point was approached. Weak staining in chorion laeve trophoblast was also detected. In situ hybridization experiments showed PAI-1 mRNA to be concentrated mainly in the decidual cells, some of which were interposed into the maternal-facing edge of the chorion laeve. Maximal labelling of the decidua occurred towards the zone of abscission. Weak expression of PAI-1 mRNA was also noted in some cells of the chorion laeve. The distribution of PAI-2 mRNA in amniochorion was also concentrated in the cells of the decidual layer, maximum expression of the mRNA was

  16. A novel exendin-4 human serum albumin fusion protein, E2HSA, with an extended half-life and good glucoregulatory effect in healthy rhesus monkeys

    International Nuclear Information System (INIS)

    Highlights: • E2HSA has an extended half-life and good plasma stability. • E2HSA could improve glucose-dependent insulin secretion. • E2HSA has excellent glucoregulatory effects in vivo. • E2HSA could potentially be used as a new long-acting GLP-1 receptor agonist for type 2 diabetes management. - Abstract: Glucagon-like peptide-1 (GLP-1) has attracted considerable research interest in terms of the treatment of type 2 diabetes due to their multiple glucoregulatory functions. However, the short half-life, rapid inactivation by dipeptidyl peptidase-IV (DPP-IV) and excretion, limits the therapeutic potential of the native incretin hormone. Therefore, efforts are being made to develop the long-acting incretin mimetics via modifying its structure. Here we report a novel recombinant exendin-4 human serum albumin fusion protein E2HSA with HSA molecule extends their circulatory half-life in vivo while still retaining exendin-4 biological activity and therapeutic properties. In vitro comparisons of E2HSA and exendin-4 showed similar insulinotropic activity on rat pancreatic islets and GLP-1R-dependent biological activity on RIN-m5F cells, although E2HSA was less potent than exendin-4. E2HSA had a terminal elimation half-life of approximate 54 h in healthy rhesus monkeys. Furthermore, E2HSA could reduce postprandial glucose excursion and control fasting glucose level, dose-dependent suppress food intake. Improvement in glucose-dependent insulin secretion and control serum glucose excursions were observed during hyperglycemic clamp test (18 h) and oral glucose tolerance test (42 h) respectively. Thus the improved physiological characterization of E2HSA make it a new potent anti-diabetic drug for type 2 diabetes therapy

  17. Glycemic Control and Chronic Dosing of Rhesus Monkeys with a Fusion Protein of Iduronidase and a Monoclonal Antibody Against the Human Insulin Receptor

    Science.gov (United States)

    Boado, Ruben J.; Hui, Eric Ka-Wai; Lu, Jeff Zhiqiang

    2012-01-01

    Hurler's syndrome, or mucopolysaccharidosis type I, is a lysosomal storage disorder caused by mutations in the gene encoding the lysosomal enzyme iduronidase (IDUA). The disease affects both peripheral tissues and the central nervous system (CNS). Recombinant IDUA treatment does not affect the CNS, because IDUA does not cross the blood-brain barrier (BBB). To enable BBB penetration, human IDUA was re-engineered as an IgG-IDUA fusion protein, where the IgG domain is a genetically engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb penetrates the brain from the blood via transport on the endogenous BBB insulin receptor and acts as a molecular Trojan horse to deliver the fused IDUA to the brain. Before human testing, the HIRMAb-IDUA fusion protein was evaluated in a 6-month weekly dosing toxicology study at doses of 0, 3, 9, and 30 mg/kg/week of the fusion protein administered to 40 rhesus monkeys. The focus of the present study is the effect of chronic high dose administration of this fusion protein on plasma glucose and long-term glycemic control. The results show that the HIRMAb has weak insulin agonist activity and causes hypoglycemia at the high dose, 30 mg/kg, after intravenous infusion in normal saline. When dextrose is added to the saline infusion solution, no hypoglycemia is observed at any dose. An intravenous glucose tolerance test performed at the end of the 6 months of chronic treatment showed no change in glucose tolerance at any dose of the HIRMAb-IDUA fusion protein. PMID:22822036

  18. Metabolism and placental transfer of /sup 125/I-proinsulin and /sup 125/I-tyrosylated C-peptide in the pregnant rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Gruppuso, P.A.; Susa, J.B.; Sehgal, P.; Frank, B.; Schwartz, R.

    1987-10-01

    /sup 125/I-Proinsulin or /sup 125/I-tyrosylated-C-peptide (/sup 125/I-tyr-CP) was administered to pregnant Rhesus monkeys by bolus followed by constant infusion to examine placental transfer of these peptides. At the end of each infusion, fetuses were exsanguinated in situ via the umbilical vein. The bolus-constant infusion technique produced a steady state in maternal plasma of immunoprecipitable label, measured using excess insulin or C-peptide antiserum. In animals infused with /sup 125/I-proinsulin, analysis of umbilical venous plasma revealed no apparent transfer to the fetus of immunoprecipitable label. In animals infused with /sup 125/I-tyr-CP, 3-13% of the umbilical venous plasma radioactivity was immunoprecipitable, representing 1.4-5.8% of the immunoprecipitable radioactivity in maternal plasma at delivery. Gel filtration chromatography of umbilical venous plasma revealed that the immunoprecipitated moiety was a fragment of /sup 125/I-tyr-CP. Analysis of maternal plasma showed that the predominant peak of radioactivity represented intact C-peptide. A peak corresponding to the fetal immunoprecipitable peak was also present. Analysis of simultaneous maternal arterial and uterine vein plasma samples showed that degradation of /sup 125/I-tyr-CP occurred across the uterus. Studies in one nonpregnant and three postpartum animals indicated that pregnancy increased the rate of metabolism of /sup 125/I-tyr-CP. When /sup 125/I-tyr-CP was incubated with trophoblastic cells in culture, degradation to a species corresponding on gel filtration to the immunoprecipitable fetal metabolite was found. We conclude that proinsulin, like insulin, does not traverse the placenta. Immunoreactive fragments of C-peptide do cross, however, and pregnancy alters the metabolism of /sup 125/I-tyr-CP, probably owing to placental degradation.

  19. Metabolism and placental transfer of 125I-proinsulin and 125I-tyrosylated C-peptide in the pregnant rhesus monkey

    International Nuclear Information System (INIS)

    125I-Proinsulin or 125I-tyrosylated-C-peptide (125I-tyr-CP) was administered to pregnant Rhesus monkeys by bolus followed by constant infusion to examine placental transfer of these peptides. At the end of each infusion, fetuses were exsanguinated in situ via the umbilical vein. The bolus-constant infusion technique produced a steady state in maternal plasma of immunoprecipitable label, measured using excess insulin or C-peptide antiserum. In animals infused with 125I-proinsulin, analysis of umbilical venous plasma revealed no apparent transfer to the fetus of immunoprecipitable label. In animals infused with 125I-tyr-CP, 3-13% of the umbilical venous plasma radioactivity was immunoprecipitable, representing 1.4-5.8% of the immunoprecipitable radioactivity in maternal plasma at delivery. Gel filtration chromatography of umbilical venous plasma revealed that the immunoprecipitated moiety was a fragment of 125I-tyr-CP. Analysis of maternal plasma showed that the predominant peak of radioactivity represented intact C-peptide. A peak corresponding to the fetal immunoprecipitable peak was also present. Analysis of simultaneous maternal arterial and uterine vein plasma samples showed that degradation of 125I-tyr-CP occurred across the uterus. Studies in one nonpregnant and three postpartum animals indicated that pregnancy increased the rate of metabolism of 125I-tyr-CP. When 125I-tyr-CP was incubated with trophoblastic cells in culture, degradation to a species corresponding on gel filtration to the immunoprecipitable fetal metabolite was found. We conclude that proinsulin, like insulin, does not traverse the placenta. Immunoreactive fragments of C-peptide do cross, however, and pregnancy alters the metabolism of 125I-tyr-CP, probably owing to placental degradation

  20. Intra-amniotic IL-1β induces fetal inflammation in rhesus monkeys and alters the regulatory T cell/IL-17 balance.

    Science.gov (United States)

    Kallapur, Suhas G; Presicce, Pietro; Senthamaraikannan, Paranthaman; Alvarez, Manuel; Tarantal, Alice F; Miller, Lisa M; Jobe, Alan H; Chougnet, Claire A

    2013-08-01

    Very low birth weight preterm newborns are susceptible to the development of debilitating inflammatory diseases, many of which are associated with chorioamnionitis. To define the effects of chorioamnionitis on the fetal immune system, IL-1β was administered intra-amniotically at ~80% gestation in rhesus monkeys. IL-1β caused histological chorioamnionitis, as well as lung inflammation (infiltration of neutrophils or monocytes in the fetal airways). There were large increases in multiple proinflammatory cytokine mRNAs in the lungs at 24 h postadministration, which remained elevated relative to controls at 72 h. Intra-amniotic IL-1β also induced the sustained expression of the surfactant proteins in the lungs. Importantly, IL-1β significantly altered the balance between inflammatory and regulatory T cells. Twenty-four hours after IL-1β injection, the frequency of CD3(+)CD4(+)FOXP3(+) T cells was decreased in lymphoid organs. In contrast, IL-17A-producing cells (CD3(+)CD4(+), CD3(+)CD4(-), and CD3(-)CD4(-) subsets) were increased in lymphoid organs. The frequency of IFN-γ-expressing cells did not change. In this model of a single exposure to an inflammatory trigger, CD3(+)CD4(+)FOXP3(+) cells rebounded quickly, and their frequency was increased at 72 h compared with controls. IL-17 expression was also transient. Interestingly, the T cell profile alteration was confined to the lymphoid organs and not to circulating fetal T cells. Together, these results suggest that the chorioamnionitis-induced IL-1/IL-17 axis is involved in the severe inflammation that can develop in preterm newborns. Boosting regulatory T cells and/or controlling IL-17 may provide a means to ameliorate these abnormalities. PMID:23794628

  1. A novel exendin-4 human serum albumin fusion protein, E2HSA, with an extended half-life and good glucoregulatory effect in healthy rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ling; Wang, Lin; Meng, Zhiyun; Gan, Hui; Gu, Ruolan; Wu, Zhuona; Gao, Lei; Zhu, Xiaoxia; Sun, Wenzhong; Li, Jian; Zheng, Ying; Dou, Guifang, E-mail: douguifang@vip.163.com

    2014-03-07

    Highlights: • E2HSA has an extended half-life and good plasma stability. • E2HSA could improve glucose-dependent insulin secretion. • E2HSA has excellent glucoregulatory effects in vivo. • E2HSA could potentially be used as a new long-acting GLP-1 receptor agonist for type 2 diabetes management. - Abstract: Glucagon-like peptide-1 (GLP-1) has attracted considerable research interest in terms of the treatment of type 2 diabetes due to their multiple glucoregulatory functions. However, the short half-life, rapid inactivation by dipeptidyl peptidase-IV (DPP-IV) and excretion, limits the therapeutic potential of the native incretin hormone. Therefore, efforts are being made to develop the long-acting incretin mimetics via modifying its structure. Here we report a novel recombinant exendin-4 human serum albumin fusion protein E2HSA with HSA molecule extends their circulatory half-life in vivo while still retaining exendin-4 biological activity and therapeutic properties. In vitro comparisons of E2HSA and exendin-4 showed similar insulinotropic activity on rat pancreatic islets and GLP-1R-dependent biological activity on RIN-m5F cells, although E2HSA was less potent than exendin-4. E2HSA had a terminal elimation half-life of approximate 54 h in healthy rhesus monkeys. Furthermore, E2HSA could reduce postprandial glucose excursion and control fasting glucose level, dose-dependent suppress food intake. Improvement in glucose-dependent insulin secretion and control serum glucose excursions were observed during hyperglycemic clamp test (18 h) and oral glucose tolerance test (42 h) respectively. Thus the improved physiological characterization of E2HSA make it a new potent anti-diabetic drug for type 2 diabetes therapy.

  2. Percutaneous absorption and skin decontamination of PCBs: In vitro studies with human skin and in vivo studies in the rhesus monkey

    International Nuclear Information System (INIS)

    Knowledge of the entry of polychlorinated biphenyls through the skin into the body and subsequent disposition aids estimation of potential for human health hazard. [14C]Aroclor 1242 and [14C]Aroclor 1254 were separately administered intravenously and topically to rhesus monkeys. Following iv administration, 30-d excretion was 39.4 +/- 5.9% urine and 16.1 +/- 0.8% feces (total 55.5 +/- 5.1%) for Aroclor 1242, and 7.0 +/- 2.2% urine and 19.7 +/- 5.8% feces (total 26.7 +/- 7.5%) for Aroclor 1254. Mineral oil and trichlorobenzene are common PCB cosolvents in transformers. Skin absorption of Aroclor 1242 was 20.4 +/- 8.5% formulated in mineral oil and 18.0 +/- 3.8% in trichlorobenzene (p greater than .05). Absorption of Aroclor 1254 was 20.8 +/- 8.3% in mineral oil and 14.6 +/- 3.6% in trichlorobenzene (p greater than .05). PCBs are thus absorbed through skin, and excretion from the body is slow. Vehicle (trichlorobenzene or mineral oil) did not affect percutaneous absorption. In vitro skin absorption in human cadaver skin did not correlate with in vivo findings. This was due to lack of PCB partition from skin into the water receptor fluid, even with addition of 6% Oleth 20 (Volpo 20) solubilizer. Skin decontamination of PCBs showed soap and water to be as effective as or better than the solvent ethanol, mineral oil, and trichlorobenzene in removing PCBs from skin. There is a dynamic time lapse for PCBs between initial skin contact and skin absorption (irreversible removal). Thus initially most PCBs could be removed from skin, but this ability decreased with time to the point where at 24 h only about 25% of the initial PCB skin dose could be recovered with skin washing

  3. PCR detection and DNA sequence analysis of the regulatory region of lymphotropic papovavirus in peripheral blood mononuclear cells of an immunocompromised rhesus macaque

    Science.gov (United States)

    Lednicky, John A.; Halvorson, Steven J.; Butel, Janet S.

    2002-01-01

    A lymphotropic papovavirus (LPV) archetypal regulatory region was amplified from DNA from the blood of an immunocompromised rhesus monkey. We believe this is the first nonserological evidence of LPV infection in rhesus monkeys.

  4. Parvalbumin increases in the medial and lateral geniculate nuclei of aged rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Daniel T Gray

    2013-11-01

    Full Text Available Subcortical auditory structures in the macaque auditory system increase their densities of neurons expressing the calcium binding protein parvalbumin (PV with age. However, it is unknown whether these increases occur in the thalamic division of the auditory system, the medial geniculate nucleus (MGN. Furthermore, it is also unclear whether these age-related changes are specific to the macaque auditory system or are generalized to other sensory systems. To address these questions, the PV immunoreactivity of the medial and lateral geniculate nuclei (LGN from seven rhesus macaques ranging in age from 15 to 35 was assessed. Densities of PV expressing neurons in the three subdivisions of the MGN and the six layers of the LGN were calculated separately using unbiased stereological sampling techniques. We found that the ventral and magnocellular subdivisions of the MGN and all six layers of the LGN increased their expressions of PV with age, although increases in the MGN were greater in magnitude than in the LGN. Together, these results suggest that the MGN shows age-related increases in PV expression as is seen throughout the macaque ascending auditory system, and that the analogous region of the visual system shows smaller increases. We conclude that, while there are some similarities between sensory systems, the age-related neurochemical changes seen throughout the macaque auditory system cannot be fully generalized to other sensory systems.

  5. 人工哺育期腹泻婴猴奇异变形杆菌的分离与鉴定%Isolation and Identification of Proteus mirabilis from Diarrheic Infant Rhesus Monkeys in the Period of Artificial Feeding

    Institute of Scientific and Technical Information of China (English)

    赵远; 杨凤梅; 陈丽雄; 禹文海; 王俊斌; 和占龙

    2012-01-01

    Objective To identify the P. mirabilis strain isolated from infant rhesus monkeys in the period of artificial feeding, and provide useful data for detection and identification of the bacteria in laboratory rhesus monkeys. Methods P. mirabilis strains isolated from infant rhesus monkeys were identified by cultural characteristics, colony morphology, staining, motility and biochemical test and serological test. Meanwhile, antibiotic sensitivity, virulence and toxin tests were conducted. Results The results of cultural characteristics, colony morphology, staining, biochemical and serological tests showed that the isolate was a strain of P. mirabilis. Effective therapeutic drugs were screened by antibiotic sensitivity test, and the disease was effectively controlled. Virulence tests showed that it is a highly pathogenic strain to mice. Conclusions The results of this study demonstrate that P. mirabilis isolated from infant monkeys is the pathogenic agent leading to their diarrhea and death. This bacteria strain is a conditional pathogen, which may cause some potential harm to researchers and laboratory rhesus monkeys. Although laboratory rhesus monkeys are allowed to be P. mirabilis carriers in our country, it is worth to pay high attention to the serious consequence of P. mirabilis infection, and it should be considered as an important issue.%目的 对一株人工哺育期引发恒河猴婴猴腹泻的奇异变形杆菌进行了鉴定,为实验猕猴疾病检测、鉴别诊断提供参考依据.方法 通过培养特性、菌落形态、染色、生化试验和血清学诊断鉴别等检查,对分离菌株进行初步鉴定,同时,对分离菌株进行致病性试验及药敏试验.结果 通过表型生物学特性鉴定,并结合血清学诊断鉴别方法,确证该分离菌株为奇异变形杆菌,应用药敏试验筛选出了高度敏感的抗菌药,控制了该病的继续发生,致病性试验证明,该分离菌株对小白鼠有高致病性.结论 分离到

  6. Increased rigidity with age in social behavior of Java-monkeys (Macaca fascicularis)

    NARCIS (Netherlands)

    Veenema, H.C.; Hooff, van J.A.R.A.M.; Gispen, W.H.; Spruijt, B.M.

    2001-01-01

    In this study we investigated the effect of aging on the structure of behavior of socially housed Java-monkeys. Indices of the sequential structure of an animal's own ongoing behavior and of its responses to behavior of other animals were calculated using an information statistic approach. These ind

  7. Increased rigidity with age in social behavior of Java-monkeys (Macaca fascicularis)

    NARCIS (Netherlands)

    Gispen, W.H.; Veenema, H.C.; Hooff, J.A.R.A.M. van; Spruijt, B.M.

    2001-01-01

    In this study we investigated the effect of aging on the structure of behavior of socially housed Java-monkeys. Indices of the sequential structure of an animal s own ongoing behavior and of its responses to behavior of other animals were calculated using an information statistic approach. These ind

  8. Nucleologenesis and embryonic genome activation are defective in interspecies cloned embryos between bovine ooplasm and rhesus monkey somatic cells

    Directory of Open Access Journals (Sweden)

    Han Yong-Mahn

    2009-07-01

    Full Text Available Abstract Background Interspecies somatic cell nuclear transfer (iSCNT has been proposed as a tool to address basic developmental questions and to improve the feasibility of cell therapy. However, the low efficiency of iSCNT embryonic development is a crucial problem when compared to in vitro fertilization (IVF and intraspecies SCNT. Thus, we examined the effect of donor cell species on the early development of SCNT embryos after reconstruction with bovine ooplasm. Results No apparent difference in cleavage rate was found among IVF, monkey-bovine (MB-iSCNT, and bovine-bovine (BB-SCNT embryos. However, MB-iSCNT embryos failed to develop beyond the 8- or 16-cell stages and lacked expression of the genes involved in embryonic genome activation (EGA at the 8-cell stage. From ultrastructural observations made during the peri-EGA period using transmission electron microscopy (TEM, we found that the nucleoli of MB-iSCNT embryos were morphologically abnormal or arrested at the primary stage of nucleologenesis. Consistent with the TEM analysis, nucleolar component proteins, such as upstream binding transcription factor, fibrillarin, nucleolin, and nucleophosmin, showed decreased expression and were structurally disorganized in MB-iSCNT embryos compared to IVF and BB-SCNT embryos, as revealed by real-time PCR and immunofluorescence confocal laser scanning microscopy, respectively. Conclusion The down-regulation of housekeeping and imprinting genes, abnormal nucleolar morphology, and aberrant patterns of nucleolar proteins during EGA resulted in developmental failure in MB-iSCNT embryos. These results provide insight into the unresolved problems of early embryonic development in iSCNT embryos.

  9. Comparative characterization of mesenchymal stem cells from different age groups of cynomolgus monkeys

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Y.Alex

    2010-01-01

    Bone marrow mesenchymal stem cells(BM-MSCs) are a potential tool for cell therapy and tissue engineering.In this study,we carried on a comparative study of the characteristics of MSCs from different age cynomolgus monkeys.A variety of factors,including donor age,must be considered before further applications,and various tests should be used to properly assess MSCs before the clinical application,especially when a prolonged culture and ex vivo expansion is necessary.

  10. Age-related pharmacokinetic changes of acetaminophen, antipyrine, diazepam, diphenhydramine, and ofloxacin in male cynomolgus monkeys and beagle dogs.

    Science.gov (United States)

    Koyanagi, Takashi; Yamaura, Yoshiyuki; Yano, Koji; Kim, Soonih; Yamazaki, Hiroshi

    2014-10-01

    1. The pharmacokinetics of acetaminophen (marker of gastric emptying), antipyrine (marker of hepatic metabolic activity and total body water), diazepam (lipophilic and highly distributed), diphenhydramine (hepatic blood flow-limited and alpha-1 acid glycoprotein bound) and ofloxacin (renally eliminated) were evaluated in cynomolgus monkeys (3-18 years old) and beagle dogs (2-11 years old) as models in elderly persons. 2. Gastric pH fluctuated with aging in monkeys and dogs. The concentration of alpha-1 acid glycoprotein appeared to be increased by aging. There were no age-related differences in the absorption rates of the drugs under the conditions used in the study. Total body fat increased and water decreased in monkeys, but these parameters did not change in dogs. 3. Hepatic blood flow decreased in both species, but a significant decrease of hepatic clearance was only seen in monkeys. Renal clearance decreased significantly with age in monkeys and showed a tendency to decrease in dogs. 4. Age-related alterations of physiological parameters in monkeys are in agreement with clinical observations in humans, except for the lack of a change in the plasma albumin concentration. Therefore, this study suggests that monkey might be a suitable animal model for prediction of age-related changes in pharmacokinetics in humans. PMID:24650193

  11. First-time rhesus monkey mothers, and mothers of sons, preferentially engage in face-to-face interactions with their infants.

    Science.gov (United States)

    Dettmer, Amanda M; Kaburu, Stefano S K; Byers, Kristen L; Murphy, Ashley M; Soneson, Emma; Wooddell, Lauren J; Suomi, Stephen J

    2016-02-01

    Face-to-face interactions between mothers and infants occur in both human and non-human primates, but there is large variability in the occurrence of these behaviors and the reason for this variability remains largely unexplored. Other types of maternal investment have been shown to be dependent on infant sex (e.g. milk production and maternal responsiveness) and maternal experience (e.g. symmetrical communication). Thus, we sought to determine whether variability in face-to-face interactions, that is, mutual gazing (MG), which are hypothesized to be important for later socio-cognitive development, could be explained by these variables. We studied 28 semi-free ranging rhesus monkey (Macaca mulatta) mother-infant dyads (6 primiparous; 12 male infants) born and reared at the Laboratory of Comparative Ethology field station at the NIH Animal Center in Poolesville, MD, across the first 90 postnatal days. Infant sex (i.e. male) was a significant predictor of maternal grooming (β ± SE = 0.359 ± 0.164, Z = 2.19, P = 0.029) whereas both parity (i.e. first time mothers) and infant sex (i.e. male) significantly predicted MG (parity: β ± SE = -0.735 ± 0.223, Z = -3.30, P < 0.001; infant sex: β ± SE = 0.436 ± 0.201, Z = 2.17, P = 0.029). Separation from the mother (outside of arm's reach) was not influenced by parity or infant sex. Together with existing literature, these findings point toward differential maternal investment for sons versus daughters. Mothers may be investing differentially in sons, behaviorally, to ensure their future social competence and thus later reproductive success. Collectively, our findings add to the literature that is beginning to identify early life experiences that may lead to sex differences in neurological and behavioral development. PMID:26581804

  12. Valores de latencia y respuestas electrofisiológicas de los diferentes componentes de los potenciales evocados auditivos del tallo cerebral en mono rhesus a diferentes intensidades (70-30 dB Latency values and electrophysiological responses of the different components of the brainstem auditory evoked potentials in rhesus monkeys at different intensities (70-30 dB

    Directory of Open Access Journals (Sweden)

    A Ibáñez-Contreras

    2012-01-01

    Full Text Available El registro de los Potenciales Evocados Auditivos de Tallo Cerebral (PEATC es sensible a las diferencias en los parámetros de estimulación, condiciones del registro y características de la especie utilizada, por lo que es imprescindible poseer valores de normalidad para cada laboratorio. El objetivo de este estudio fue obtener datos normativos acerca de los valores de latencia y de las respuestas electrofisiológicas de los diferentes componentes de los PEATC en el mono rhesus, en diferentes intensidades (70-30 dB. Se utilizaron 14 monos rhesus (Macaca mulatta con una edad promedio de siete años, divididos en siete machos con un peso promedio de 7 kg y siete hembras con un peso aproximado de 5 kg. Los PEATC se obtuvieron mediante la estimulación de los oídos con "clicks" de rarefacción a 70, 50 y 30 dB de intensidad. La actividad eléctrica cerebral fue recogida por medio de electrodos de disco, colocados en las derivaciones Cz (+, A1, A2 (- y Fz como tierra, según el sistema 10/20 internacional. Se observaron cuatro ondas constantes y definidas en las diferentes intensidades utilizadas, tanto en machos como en hembras. Debido a que no se encontraron diferencias significativas en t de Student por aferencias separadas, se unificaron las aferencias, evaluando las latencias absolutas de las cuatro ondas obtenidas, así como los intervalos I-II, II-IV y I-IV en los 14 sujetos, en las diferentes intensidades.The records of the Brainstem Auditory Evoked Potentials (BAEPs are sensitive to differences in stimulation parameters, conditions of registration and characteristics of the species, so it is essential to have normal values for each laboratory. The aim of our study was to obtain normative data on the latency values and electrophysiological responses of the different components of the BAEPs in the rhesus monkey, at different intensities (70-30 dB. This study was performed using 14 non-human primates of the Macaca mulatta species, with an

  13. Early rearing interacts with temperament and housing to influence the risk for motor stereotypy in rhesus monkeys (Macaca mulatta)

    OpenAIRE

    Vandeleest, Jessica J.; McCowan, Brenda; Capitanio, John P.

    2011-01-01

    Laboratory and zoo housed non-human primates sometimes exhibit abnormal behaviors that are thought to reflect reduced wellbeing. Previous research attempted to identify risk factors to aid in the prevention and treatment of these behaviors, and focused on demographic (e.g. sex or age) and experience-related (e.g. single housing or nursery rearing) factors. However, not all animals that display abnormal behavior possess these risk factors and some individuals that possess a risk factor do not ...

  14. Effect of IL-7 Therapy on Naive and Memory T Cell Homeostasis in Aged Rhesus Macaques.

    Science.gov (United States)

    Okoye, Afam A; Rohankhedkar, Mukta; Konfe, Audrie L; Abana, Chike O; Reyes, Matthew D; Clock, Joseph A; Duell, Derick M; Sylwester, Andrew W; Sammader, Partha; Legasse, Alfred W; Park, Byung S; Axthelm, Michael K; Nikolich-Žugich, Janko; Picker, Louis J

    2015-11-01

    Aging is associated with gradual deterioration of adaptive immune function, a hallmark of which is the profound loss of naive T cells (TN) associated with decline in thymic output and export of new cells into the peripheral T cell pool. Because the lymphotropic cytokine IL-7 plays crucial roles in both development of TN in the thymus and TN homeostasis in the periphery, we sought to determine the extent to which therapeutic administration of IL-7 could reverse TN deficiency in aging rhesus macaques (RM), either by enhancement of the demonstrably reduced thymopoiesis or by peripheral TN expansion. Our results indicate that treatment of both adult (8-15 y) and old (>20 y) RM with recombinant simian IL-7 (rsIL-7) results in only transient increases in peripheral CD4(+) and CD8(+) TN numbers with no long-term benefit, even with repeated therapy. This transient effect was due to peripheral TN expansion and not enhanced thymic function, and appeared to be limited by induction of IL-7 nonresponsiveness. However, rsIL-7 therapy had a more promising effect on the central memory T cell (TCM) population (both CD4(+) and CD8(+)) in adult and old RM, doubling the numbers of these cells in circulation and maintaining this larger population long term. IL-7 therapy did not reduce TCR diversity of the memory T cell compartment, suggesting that rsIL-7-induced expansion was symmetrical. Thus, although rsIL-7 failed to counter age-associated TN loss, the ability of this therapy to expand clonotypically diverse CD4(+) and CD8(+) TCM populations might potentially improve adaptive immune responsiveness in the elderly. PMID:26416281

  15. The Physiological Effect of Human Grooming on the Heart Rate and the Heart Rate Variability of Laboratory Non-Human Primates: A Pilot Study in Male Rhesus Monkeys

    OpenAIRE

    Grandi, Laura Clara; Ishida, Hiroaki

    2015-01-01

    Grooming is a widespread, essential, and complex behavior with social and affiliative valence in the non-human primate world. Its impact at the autonomous nervous system level has been studied during allogrooming among monkeys living in a semi-naturalistic environment. For the first time, we investigated the effect of human grooming to monkey in a typical experimental situation inside laboratory. We analyzed the autonomic response of male monkeys groomed by a familiar human (experimenter), in...

  16. 实验性2型糖尿病恒河猴模型的构建及其部分临床特征分析%Establishment of a rhesus monkey model of type 2 diabetes mellitus and analysis of some of its clinical features

    Institute of Scientific and Technical Information of China (English)

    鲁帅尧; 和占龙; 杨凤梅; 禹文海; 赵远; 李艳艳; 王俊斌; 陈丽雄; 乞素冬

    2013-01-01

    目的 构建2型糖尿病(T2DM)恒河猴模型,使之成为研究人类T2DM的有效替身.方法 以高糖高脂饮食为基础,在出现高脂血症和肥胖状态后注射35 mg/kg的链脲佐菌素(STZ),测定体重指数、血脂、空腹血糖、胰岛素、胰岛素抵抗指数、尿糖和口服葡萄糖耐量试验等,分析其部分临床特征.结果 T2DM模型组体重指数(BMI)大于35达到重度肥胖,有高脂血症的特点,空腹血糖、胰岛素和胰岛素抵抗指数显著增高(P<0.01),尿糖检测呈阳性,葡萄糖耐量受损并且空腹血糖高于7 mmol/L、2h的血糖水平高于11.1 mmoL/L,胰岛有轻度损伤和病变.结论 通过部分临床特征分析,T2DM模型组具有典型的T2DM临床特征,可成为T2DM研究的有效模型.%Objective To establish a type 2 diabetic (T2DM) model in rhesus monkey,and provide an effective substitute for the study of human T2DM.Methods Twelve adult rhesus monkeys aged 6-10 years were divided into three groups:T2DM group,high-fat diet group and normal control group,4 monkeys in each group.Based on high-glucose and fat diet feeding,to give streptozotocin (STZ) injection in a dose of 35 mg/kg body weight after the appearance of hyperlipidemia and obesity status in the monkeys.The body mass index (BMI),lipid profile,fasting blood glucose,insulin,insulin resistance index,urine sugar and oral glucose tolerance were measured,and some clinical features in the monkeys were analyzed.Results The BMI higher than 35 was considered as severe obesity,showing characteristics of hyperlipidemia,with significantly elevated blood glucose,insulin and insulin resistance index (P < 0.01),positive urine sugar,impaired glucose tolerance,and having fasting glucose higher than 7 mmol/L and two-hour glucose level higher than 11.1 mmol/L,and had mild pathological alterations of pancreatic islets in the T2DM model group.Conclusions Analysis of some clinical features shows that the monkey models exhibit typical clinical

  17. Early rearing interacts with temperament and housing to influence the risk for motor stereotypy in rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Vandeleest, Jessica J; McCowan, Brenda; Capitanio, John P

    2011-06-01

    Laboratory and zoo housed non-human primates sometimes exhibit abnormal behaviors that are thought to reflect reduced wellbeing. Previous research attempted to identify risk factors to aid in the prevention and treatment of these behaviors, and focused on demographic (e.g. sex or age) and experience-related (e.g. single housing or nursery rearing) factors. However, not all animals that display abnormal behavior possess these risk factors and some individuals that possess a risk factor do not show behavioral abnormalities. We hypothesized that other aspects of early experience and individual characteristics might identify animals that were more likely to display one specific abnormal behavior, motor stereotypy (MS). Using logistic regression we explored the influence of early rearing (involving four different types of rearing conditions), and variation in temperament, on likelihood of displaying MS while controlling for previously identified risk factors. Analyses indicated that having a greater proportion of life lived indoors, a greater proportion of life-indoors singly-housed, and a greater number of anesthesias and blood draws significantly increased the risk of displaying MS (P < 0.001). Rearing condition failed to independently predict the display of MS; however significant interactions indicated that single housing had a greater impact on risk for indoor-reared animals versus outdoor-reared animals, and for indoor mother-reared animals versus nursery-reared animals. There were no main effects of temperament, although interactions with rearing were evident: scoring high on Gentle or Nervous was a risk factor for indoor-reared animals but not outdoor-reared animals. The final model accounted for approximately 69.3 % of the variance in the display of MS, and correctly classified 90.6% of animals. These results indicate that previously identified risk factors may impact animals differently depending on the individual's early rearing condition. These results are

  18. Reduced information transmission in the internal segment of the globus pallidus of 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine-induced rhesus monkey models of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Yan He; Jue Wang; Guodong Gao; Guangjun Zhang

    2012-01-01

    Rhesus monkey models of Parkinson's disease were induced by injection of N-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine. Neural firings were recorded using microelectrodes placed in the internal segment of the globus pallidus. The wavelets and power spectra show gradual power reduction during the disease process along with increased firing rates in the Parkinson's disease state. Singular values of coefficients decreased considerably during tremor-related activity as well as in the Parkinson's disease state compared with normal signals, revealing that higher-frequency components weaken when Parkinson's disease occurs. We speculate that the death of neurons could be reflected by irregular frequency spike trains, and that wavelet packet decomposition can effectively detect the degradation of neurons and the loss of information transmission in the neural circuitry.

  19. Three-dimensional organization of otolith-ocular reflexes in rhesus monkeys. I. Linear acceleration responses during off-vertical axis rotation

    Science.gov (United States)

    Angelaki, D. E.; Hess, B. J.

    1996-01-01

    1. The dynamic properties of otolith-ocular reflexes elicited by sinusoidal linear acceleration along the three cardinal head axes were studied during off-vertical axis rotations in rhesus monkeys. As the head rotates in space at constant velocity about an off-vertical axis, otolith-ocular reflexes are elicited in response to the sinusoidally varying linear acceleration (gravity) components along the interaural, nasooccipital, or vertical head axis. Because the frequency of these sinusoidal stimuli is proportional to the velocity of rotation, rotation at low and moderately fast speeds allows the study of the mid-and low-frequency dynamics of these otolith-ocular reflexes. 2. Animals were rotated in complete darkness in the yaw, pitch, and roll planes at velocities ranging between 7.4 and 184 degrees/s. Accordingly, otolith-ocular reflexes (manifested as sinusoidal modulations in eye position and/or slow-phase eye velocity) were quantitatively studied for stimulus frequencies ranging between 0.02 and 0.51 Hz. During yaw and roll rotation, torsional, vertical, and horizontal slow-phase eye velocity was sinusoidally modulated as a function of head position. The amplitudes of these responses were symmetric for rotations in opposite directions. In contrast, mainly vertical slow-phase eye velocity was modulated during pitch rotation. This modulation was asymmetric for rotations in opposite direction. 3. Each of these response components in a given rotation plane could be associated with an otolith-ocular response vector whose sensitivity, temporal phase, and spatial orientation were estimated on the basis of the amplitude and phase of sinusoidal modulations during both directions of rotation. Based on this analysis, which was performed either for slow-phase eye velocity alone or for total eye excursion (including both slow and fast eye movements), two distinct response patterns were observed: 1) response vectors with pronounced dynamics and spatial/temporal properties

  20. Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys

    Science.gov (United States)

    Gazzaley, A. H.; Thakker, M. M.; Hof, P. R.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1997-01-01

    The perforant path, which consists of the projection from the layer II neurons of the entorhinal cortex to the outer molecular layer of the dentate gyrus, is a critical circuit involved in learning and memory formation. Accordingly, disturbances in this circuit may contribute to age-related cognitive deficits. In a previous study, we demonstrated a decrease in N-methyl-D-aspartate receptor subunit 1 immunofluorescence intensity in the outer molecular layer of aged macaque monkeys. In this study, we used the optical fractionator, a stereological method, to determine if a loss of layer II neurons occurred in the same animals in which the N-methyl-D-aspartate receptor subunit 1 alteration was observed. Our results revealed no significant differences in the number of layer II neurons between juvenile, young adult, and aged macaque monkeys. These results suggest that the circuit-specific decrease in N-methyl-D-aspartate receptor subunit 1 reported previously occurs in the absence of structural compromise of the perforant path, and thus may be linked to an age-related change in the physiological properties of this circuit.

  1. Motivational Shifts in Aging Monkeys and the Origins of Social Selectivity.

    Science.gov (United States)

    Almeling, Laura; Hammerschmidt, Kurt; Sennhenn-Reulen, Holger; Freund, Alexandra M; Fischer, Julia

    2016-07-11

    As humans age, they become more selective regarding their personal goals [1] and social partners [2]. Whereas the selectivity in goals has been attributed to losses in resources (e.g., physical strength) [3], the increasing focus on emotionally meaningful partners is, according to socioemotional selectivity theory, driven by the awareness of one's decreasing future lifetime [2]. Similar to humans, aging monkeys show physical losses [4] and reductions in social activity [2, 5-7]. To disentangle a general resource loss and the awareness of decreasing time, we combined field experiments with behavioral observations in a large age-heterogeneous population of Barbary macaques (Macaca sylvanus) at La Forêt des Singes. Novel object tests revealed a loss of interest in the nonsocial environment in early adulthood, which was modulated by the availability of a food reward. Experiments using vocal and visual representations of social partners indicated that monkeys maintained an interest in social stimuli and a preferential interest in friends and socially important individuals into old age. Old females engaged in fewer social interactions, although other group members continued to invest in relationships with them. Consequently, reductions in sociality were not due to a decrease in social interest. In conclusion, some of the motivational shifts observed in aging humans, particularly the increasing focus on social over nonsocial stimuli, may occur in the absence of a limited time perspective and are most likely deeply rooted in primate evolution. Our findings highlight the value of nonhuman primates as valuable models for understanding human aging [8, 9]. PMID:27345168

  2. Differences of monkey and human overt attention under natural conditions

    OpenAIRE

    Einhäuser, Wolfgang; Kruse, Wolfgang; Hoffmann, Klaus-Peter; König, Peter

    2006-01-01

    Rhesus monkeys are widely used as animal models of human attention. Such research rests upon the assumption that similar mechanisms underlie attention in both species. Here, we directly compare the influence of low-level stimulus features on overt attention in monkeys and humans under natural conditions. We recorded eye-movements in humans and rhesus monkeys during free-viewing of natural images. We find that intrinsic low-level features, such luminance-contrast, texture-contrast and...

  3. 恒河猴骨髓来源未成熟树突状细胞的培养及鉴定%Culture and identification of immature dendritic cells from rhesus monkey myeloid

    Institute of Scientific and Technical Information of China (English)

    支良; 陈鹏; 李朝战; 李昌亮; 关兴; 褚朋; 阿永俊

    2015-01-01

    目的:建立一种体外诱导恒河猴骨髓CD34+细胞分化为树突状细胞( DC)的方法,并对其细胞形态及表面标志进行鉴定。方法用免疫磁珠分选系统( MACS)分选恒河猴骨髓细胞,收集高纯度的CD34+造血干细胞;加入重组粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素4(IL-4)及肿瘤坏死因子-α(TNF-α),诱导其分化为骨髓来源的树突状细胞,并采用电镜观察细胞形态。用树突状细胞表面标志CD1a及成熟树突状细胞( mDC)表面标志CD83流式抗体染色后分析。结果细胞因子诱导6 d后成功培养出表面呈绒毛状和树枝状突起的典型DC样细胞,流式细胞术分析结果显示92.35%的细胞为DC,27.61%的细胞为mDC。结论用此方法可在体外培养出高纯度且典型的恒河猴骨髓源性未成熟树突状细胞( imDC),为进一步研究其生物学特性及功能奠定了基础。%Objective To develop a method for culturing dendritic cells ( DC ) from rhesus monkey bone marrow CD34 +cells, and identify the cells by morphological observation and cell surface marker detection .Methods To screen rhesus monkey bone marrow cells using a magnetic activated cell sorting (MACS) system then to collect highly purified CD34+hematopoietic stem cells .Recombinant granulocyte macrophage colony stimulating factor (GM-CSF), interleukin-4 ( IL-4) and tumor necrosis factor-α( TNF-α) were applied to isolate CD 34+hematopoietic stem cells to induce bone marrow-derived DCs .Morphological change of cells was observed under an electron microscope , and cell surface molecules were detected using flow cytometry after cells were stained with DC surface marker CD 1a and ma-ture DC surface marker CD83.Results Typical DCs with surface villous and dendritic protrusions were identified 6 days after cytokine treatment .92.35%of the cultured cells were DC and 27.61%of the cultured cells were mature DCs ( m

  4. 超声乳化致恒河猴角膜内皮损伤动物模型的建立%Model establishment of corneal endothelial injury by phacoemulsification in Rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    朱勤; 肖中男; 孙晓梅; 胡敏; 刘海; 胡竹林

    2013-01-01

    目的 建立超声乳化致恒河猴角膜内皮损伤的动物模型.方法 健康成年恒河猴4只,右眼用于实验.术中超声头斜面向角膜内表面,负压150 mmHg(1 kPa=7.5 mm-Hg)、流量25 mL·min-1、能量80%、距离角膜内表面0.1 ~0.2 mm的条件下持续5 min,并不断摆动超声头破坏角膜内表面,位置为角膜中央直径7 ~9 mm处.用I/A吸出透明晶状体皮质.术后当时、1周、2周、3周、4周行术眼前段照相后分别摘除术眼角膜,行扫描电镜观察角膜内皮细胞形态.结果 超声乳化损伤角膜内皮细胞后,角膜透明度随时间延长逐渐下降,术后4周时出现明显角膜混浊水肿.扫描电镜下可见随着时间推移,受损角膜内皮细胞逐渐水肿,并从后弹力层脱落,术后4周时角膜内皮细胞已基本脱落,见裸露的后弹力层.结论 本实验通过超声乳化仪建立了恒河猴角膜内皮损伤的动物模型,并且本模型具有可重复性、对内皮以外组织损伤小及简单易行的特点.%Objective To establish a model of corneal endothelial injury by phacoemulsification in Rhesus monkeys. Methods Right eyes of four healthy adult rhesus monkeys were selected. Then ultrasonic emulsification operation was performed to damage corneal endothelial cells with the inclined surface of ultrasound heads facing the corneal inner surface, the ultrasonic emulsification operation lasted for 5 minutes with a negative pressure of 150 mmHg (1kPa = 7. 5 mmHg) ,flow 25 mL · min"' and 80% of energy, and the ultrasonic head 0.1 - 0. 2 mm from the corneal inner surface and constantly oscillating to damage the surface of the corneal endothelium at a center zone with a diameter of 7 - 9 mm. Then transparent crystals cortex was sucked out with I/A. Immediately after surgery,and 1 week,2 weeks,3 weeks,4 weeks after surgery,anterior segment photography were performed on the objective eyes, then the cornea of objective eyes were excised to observe the corneal

  5. Rhesus Macaque Rhadinovirus-Associated Disease

    OpenAIRE

    Estep, Ryan D.; Wong, Scott W.

    2013-01-01

    Rhesus macaque rhadinovirus (RRV) is a gamma-2 herpesvirus that naturally infects rhesus macaque (RM) monkeys and is closely related to human herpesvirus-8 (HHV-8)/Kaposi’s sarcoma-associated herpesvirus (KSHV). Infection of immunodeficient RM induces disease in infected RM that resembles KSHV-associated pathologies. Importantly, RRV possesses homologues of KSHV ORFs that are postulated to play a role in disease development. As such, RRV has emerged as a prominent in vivo model system for exa...

  6. Application of a beta microprobe for quantification of regional cerebral blood flow with 15O-water and PET in rhesus monkeys

    International Nuclear Information System (INIS)

    A beta microprobe was successfully applied to monitor arterial input function for quantification of regional cerebral blood flow (rCBF) in the monkey brain with 15O-water and positron emission tomography (PET). The sensitivity of the probe was approximately 0.83 to 1.67 cps/kBq/ml depending on the studies. A preliminary study was performed to find a suitable use and to evaluate the performance of the system and data analysis procedure. The results showed that dispersion correction of measured input function was unnecessary if microprobes were connected directly to the arterial catheter. Then multiple CBF measurements were done in three monkeys under anesthesia. Identical regions of interest were placed with the aid of magnetic resonance imaging (MRI) of each monkey and rCBF values were estimated. Estimated rCBFs were reproducible for several measurements. The mean CBF value for a pentobarbital anesthetized monkey was 46.0 ml/min/100 g (PaCO2=46.3 mmHg). This shows that the use of the beta microprobe for quantification of rCBF with PET was validated. The lack of a need for dispersion correction of observed input function is an advantage with the beta microprobe system because the probes are small enough to be placed near the arterial sampling site. (author)

  7. Evolutionary and biomedical insights from the rhesus macaque genome

    DEFF Research Database (Denmark)

    Gibbs, Richard A; Rogers, Jeffrey; Katze, Michael G;

    2007-01-01

    The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedi...

  8. Pharmacokinetic modeling: Prediction and evaluation of route dependent dosimetry of bisphenol A in monkeys with extrapolation to humans

    International Nuclear Information System (INIS)

    A physiologically based pharmacokinetic (PBPK) model was developed for bisphenol A (BPA) in adult rhesus monkeys using intravenous (iv) and oral bolus doses of 100 μg d6-BPA/kg (). This calibrated PBPK adult monkey model for BPA was then evaluated against published monkey kinetic studies with BPA. Using two versions of the adult monkey model based on monkey BPA kinetic data from and , the aglycone BPA pharmacokinetics were simulated for human oral ingestion of 5 mg d16-BPA per person (Völkel et al., 2002). Völkel et al. were unable to detect the aglycone BPA in plasma, but were able to detect BPA metabolites. These human model predictions of the aglycone BPA in plasma were then compared to previously published PBPK model predictions obtained by simulating the Völkel et al. kinetic study. Our BPA human model, using two parameter sets reflecting two adult monkey studies, both predicted lower aglycone levels in human serum than the previous human BPA PBPK model predictions. BPA was metabolized at all ages of monkey (PND 5 to adult) by the gut wall and liver. However, the hepatic metabolism of BPA and systemic clearance of its phase II metabolites appear to be slower in younger monkeys than adults. The use of the current non-human primate BPA model parameters provides more confidence in predicting the aglycone BPA in serum levels in humans after oral ingestion of BPA. -- Highlights: ► A bisphenol A (BPA) PBPK model for the infant and adult monkey was constructed. The hepatic metabolic rate of BPA increased with age of the monkey. ► The systemic clearance rate of metabolites increased with age of the monkey. ► Gut wall metabolism of orally administered BPA was substantial across all ages of monkeys. ► Aglycone BPA plasma concentrations were predicted in humans orally given oral doses of deuterated BPA.

  9. Serial nerve conduction studies of the tail of rhesus monkey ( Macaca mulatta and potential implications for interpretation of human neurophysiological studies

    Directory of Open Access Journals (Sweden)

    Graham William

    2007-01-01

    Full Text Available It is well accepted in clinical medicine that nerve conduction studies are helpful in the diagnosis of diabetic peripheral neuropathy. However, some clinicians utilize serial nerve conduction studies to make inferences regarding the progression of peripheral neuropathy. The validity of this clinical construct has not been established. In order to determine the variability in serial nerve conduction studies, sensory and motor responses were obtained from the caudal nerve of the tail of a diabetic monkey. In particular, the sensory and motor nerve conduction studies were obtained on seven separate occasions over a period of 4.5 months in a diabetic Macaca mulatta monkey. The coefficient of variation in the motor onset latency, motor amplitude, sensory onset latency and sensory amplitude was 10.7%, 56.4%, 4.2% and 23.4%, respectively. These results suggest that physicians should be cautious in making clinical inferences based on the changes in serial nerve conduction studies.

  10. In vivo positron emission tomography studies on the novel nicotinic receptor agonist [11C]MPA compared with [11C]ABT-418 and (S)(-)[11C]nicotine in Rhesus monkeys

    International Nuclear Information System (INIS)

    The novel 11C-labeled nicotinic agonist (R,S)-1-[11C]methyl-2(3-pyridyl)azetidine ([11C]MPA) was evaluated as a positron emission tomography (PET) ligand for in vivo characterization of nicotinic acetylcholine receptors in the brain of Rhesus monkeys in comparison with the nicotinic ligands (S)-3-methyl-5-(1-[11C]methyl-2-pyrrolidinyl)isoxazol ([11C]ABT-418) and (S)(-)[11C]nicotine. The nicotinic receptor agonist [11C]MPA demonstrated rapid uptake into the brain to a similar extent as (S)(-) [11C]nicotine and [11C]ABT-418. When unlabeled (S)(-)nicotine (0.02 mg/kg) was administered 5 min before the radioactive tracers, the uptake of [11C]MPA was decreased by 25% in the thalamus, 19% in the temporal cortex, and 11% in the cerebellum, whereas an increase was found for the uptake of (S)(-)[11C]nicotine and [11C]ABT-418. This finding indicates specific binding of [11C]MPA to nicotinic receptors in the brain in a simple classical displacement study. [11C]MPA seems to be a more promising radiotracer than (S)(-)[11C]nicotine or [11C]ABT-418 for PET studies to characterize nicotinic receptors in the brain

  11. Synthesis of [11C-methyl]-(-)-OSU6162, its regional brain distribution and some pharmacological effects of (-)-OSU6162 on the dopaminergic system studied in the rhesus monkey by positron emission tomography

    International Nuclear Information System (INIS)

    The labelling of the presynaptic dopamine receptor antagonist (-)-OSU6162, ((S)-(-)-3-(3-(methylsulfonyl)phenyl)-1-propylpiperidine) was performed by an alkylation with [11C]methyl iodide of the thio anion (-)-OSU1281, followed by a selective oxidation to the corresponding methyl sulfone, [11C-methyl]-(-)-OSU6162. The total radiochemical yield calculated from the produced [11C]carbon dioxide to final product was about 25% and the time of synthesis was in the range of 40 min from end of bombardment. The synthesis of the precursor, (-)-OSU1281, was performed from (-)-3PPP in a three-step synthesis. The regional brain distribution of (-)-OSU6162 radiolabelled with 11C was studied in rhesus monkeys by means of positron emission tomography, PET. [11C-Methyl]-(-)-OSU6162 was rapidly and uniformly distributed to gray matters of the brain, and no decrease of radioactivity uptake in the brain was seen after pretreatment with 1 to 3 mg/kg/h of (-)-OSU6162. The effect of doses of 1 to 3 mg/kg/h of (-)-OSU6162 on the dopamine binding was studied by PET using [11C-methyl]raclopride. Radioactivity in the striatum was significantly and dose-dependently decreased by (-)-OSU6162 (r = 0.88), supporting competition with dopamine for selective binding to dopamine receptors

  12. 实验性高脂血症恒河猴模型的初步建立及分析%Establishment and Analysis of Experimental Hyperlipidemia Model in Rhesus Monkey

    Institute of Scientific and Technical Information of China (English)

    杨凤梅; 李艳艳; 鲁帅尧; 赵远; 禹文海; 陈丽雄; 王俊斌; 和占龙

    2012-01-01

    Objective To establish Rhesus monkey model of hyperlipidemia to provide reliable animal model for the study of human hyperlipidemia. Methods Designed high fat experimental feed formulations and detected its nutrients to feed Rhesus monkey to arouse hyperlipidemias. 2 mouths、4 mouths、6mouths later, we monitored the body weight, serum total cholesterol ( TC ) , triglyceride ( TG ) , high-density lipoprotein cholesterol ( HDL-C ) , low density lipoprotein cholesterol ( LDL-C) ,and analyzed the trend of each index above. Results When it was 2 moths and 4 months later,the feed intake and energy intake of model group were lower than control group(P 0. 05 ) ; When it was 6 moths, the feed intake and energy intake of model group was not significantly different from that of the control group, and the body weight of model group were significantly different from that of the control group ( P 0. 05 ). When it was 4 moths later,the indexes of TC ,TG, LDL-C of the model group were significantly different from that of the control group( P 0. 05 ). According to the monitoring, TC and LDL-C showed a increase trend, TG showed a gradual recovery after the first descending trend, and the HDL-C was not significantly changed. Conclusion Rhesus monkeys of the model group has a feature of high cholesterol and high low-density lipoprotein cholesterol. The paper has initialy established Rhesus monkey model of experimental hyperlipidemia.%目的 建立实验性高脂血症恒河猴模型,为人类高脂血症研究提供理想动物模型.方法 设计高脂实验饲料配方并检测常规营养成分,用高脂饲料诱导实验性高脂血症恒河猴模型,分别在2个月、4个月、6个月后监测体重、血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白( HDL-C)、低密度脂蛋白(LDL-C)等指标,对其血脂指标的变化趋势进行分析.结果 模型组在实验2个月、4个月时的日采食量和摄入能量均低于对照组(P<0.05),

  13. Kinetics of naphthalene metabolism in target and non-target tissues of rodents and in nasal and airway microsomes from the Rhesus monkey

    International Nuclear Information System (INIS)

    Naphthalene produces species and cell selective injury to respiratory tract epithelial cells of rodents. In these studies we determined the apparent Km, Vmax, and catalytic efficiency (Vmax/Km) for naphthalene metabolism in microsomal preparations from subcompartments of the respiratory tract of rodents and non-human primates. In tissues with high substrate turnover, major metabolites were derived directly from naphthalene oxide with smaller amounts from conjugates of diol epoxide, diepoxide, and 1,2- and 1,4-naphthoquinones. In some tissues, different enzymes with dissimilar Km and Vmax appeared to metabolize naphthalene. The rank order of Vmax (rat olfactory epithelium > mouse olfactory epithelium > murine airways ≫ rat airways) correlated well with tissue susceptibility to naphthalene. The Vmax in monkey alveolar subcompartment was 2% that in rat nasal olfactory epithelium. Rates of metabolism in nasal compartments of the monkey were low. The catalytic efficiencies of microsomes from known susceptible tissues/subcompartments are 10 and 250 fold higher than in rat airway and monkey alveolar subcompartments, respectively. Although the strong correlations between catalytic efficiencies and tissue susceptibility suggest that non-human primate tissues are unlikely to generate metabolites at a rate sufficient to produce cellular injury, other studies showing high levels of formation of protein adducts support the need for additional studies. - Highlights: • Naphthalene is metabolized with high catalytic efficiency in susceptible tissue. • Naphthalene is metabolized at low catalytic efficiency in non-susceptible tissue. • Respiratory tissues of the non human primate metabolize naphthalene slowly

  14. Hallazgos de anticuerpos contra Leptospira sp., serovariedades Panama, Lai, Australis, Shermani y Patoc, en un grupo de monos rhesus (Macaca mulatta en condiciones de cautiverio Antibodies findings against Leptospira sp., of the serovars Panama, Lai, Australis, Shermani, and Patoc, in a group of rhesus monkeys (Macaca mulatta in conditions of captivity

    Directory of Open Access Journals (Sweden)

    A Ibáñez-Contreras

    2010-01-01

    Full Text Available La leptospirosis ha emergido como una importante enfermedad infecciosa, lo que ha ocurrido en diferentes entornos desde urbanos hasta medios naturales; los portadores son animales salvajes o domésticos. El objetivo fue evaluar la presencia de anticuerpos contra Leptospira en monos rhesus en condiciones de bioterio. Se utilizaron 59 monos de diferentes etapas fisiológicas. Se determinaron anticuerpos contra Leptospira a partir de la prueba de aglutinación microscópica (TAM, utilizando como antígenos 25 serovariedades de Leptospira. Se observó que de los 59 animales, únicamente el 30,50% reaccionaron contra una o más serovariedades de Leptospira. En este trabajo se determinaron anticuerpos contra cuatro serovariedades de Leptospira: Panama, Lai, Australis y Shermani, consideradas como patógenas, y once de las muestras reaccionaron contra la serovariedad Patoc, considerada no patógena y saprófita. Ninguno de los animales que resultaron positivos contra Leptospira presentó signos clínicos compatibles con leptospirosis.During the last decade leptospirosis has emerged as a worldwide and very important infectious disease, affecting different environments from urban to rural, with carriers usually being wild or domestic animals. The objective of this study was to evaluate the presence of antibodies against Leptospira in rhesus monkeys (Macaca mulatta in a Research Center. Fifty nine non-human primates of different physiological stages were studied. The animals were held in groups and in individual cages. Blood samples were obtained from the saphenous vein to determine the presence of antibodies through the microscopic agglutination test (MA, using twenty five serovars of Leptospira as antigens. It was observed that 18 out of the 59 monkeys (30.50% reacted against one or more serovars of Leptospira. In this study, antibodies of 4 serovars of Leptospira, (Panama, Lai, Australis, and Shermani were detected. All 4 serovars were considered

  15. The effects of normal aging on myelinated nerve fibers in monkey central nervous system

    Directory of Open Access Journals (Sweden)

    Alan Peters

    2009-07-01

    Full Text Available The effects of aging on myelinated nerve fibers of the central nervous system are complex. Many myelinated nerve fibers in white matter degenerate and are lost, leading to some disconnections between various parts of the central nervous system. Other myelinated nerve fibers are affected differently, because only their sheaths degenerate, leaving the axons intact. Such axons are remyelinated by a series of internodes that are much shorter than the original ones and are composed of thinner sheaths. Thus the myelin-forming cells of the central nervous system, the oligodendrocytes, remain active during aging. Indeed, not only do these neuroglial cell remyelinate axons, with age they also continue to add lamellae to the myelin sheaths of intact nerve fibers, so that sheaths become thicker. It is presumed that the degeneration of myelin sheaths is due to the degeneration of the parent oligodendrocyte, and that the production of increased numbers of internodes as a consequence of remyelination requires additional oligodendrocytes. Whether there is a turnover of oligodendrocytes during life has not been studied in primates, but it has been established that over the life span of the monkey, there is a substantial increase in the numbers of oligodendrocytes. While the loss of some myelinated nerve fibers leads to some disconnections, the degeneration of other myelin sheaths and the subsequent remyelination of axons by shorter internodes slow down the rate conduction along nerve fibers. These changes affect the integrity and timing in neuronal circuits, and there is evidence that they contribute to cognitive decline.

  16. Kinetics of naphthalene metabolism in target and non-target tissues of rodents and in nasal and airway microsomes from the Rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Buckpitt, Alan, E-mail: arbuckpitt@ucdavis.edu [Department of Molecular Biosciences, School of Veterinary Medicine, UC Davis, Davis, CA 95616 (United States); Morin, Dexter [Department of Molecular Biosciences, School of Veterinary Medicine, UC Davis, Davis, CA 95616 (United States); Murphy, Shannon; Edwards, Patricia; Van Winkle, Laura [Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, UC Davis, Davis, CA 95616 (United States); Center for Health and the Environment, UC Davis, Davis, CA 95616 United States (United States)

    2013-07-15

    Naphthalene produces species and cell selective injury to respiratory tract epithelial cells of rodents. In these studies we determined the apparent K{sub m}, V{sub max}, and catalytic efficiency (V{sub max}/K{sub m}) for naphthalene metabolism in microsomal preparations from subcompartments of the respiratory tract of rodents and non-human primates. In tissues with high substrate turnover, major metabolites were derived directly from naphthalene oxide with smaller amounts from conjugates of diol epoxide, diepoxide, and 1,2- and 1,4-naphthoquinones. In some tissues, different enzymes with dissimilar K{sub m} and V{sub max} appeared to metabolize naphthalene. The rank order of V{sub max} (rat olfactory epithelium > mouse olfactory epithelium > murine airways ≫ rat airways) correlated well with tissue susceptibility to naphthalene. The V{sub max} in monkey alveolar subcompartment was 2% that in rat nasal olfactory epithelium. Rates of metabolism in nasal compartments of the monkey were low. The catalytic efficiencies of microsomes from known susceptible tissues/subcompartments are 10 and 250 fold higher than in rat airway and monkey alveolar subcompartments, respectively. Although the strong correlations between catalytic efficiencies and tissue susceptibility suggest that non-human primate tissues are unlikely to generate metabolites at a rate sufficient to produce cellular injury, other studies showing high levels of formation of protein adducts support the need for additional studies. - Highlights: • Naphthalene is metabolized with high catalytic efficiency in susceptible tissue. • Naphthalene is metabolized at low catalytic efficiency in non-susceptible tissue. • Respiratory tissues of the non human primate metabolize naphthalene slowly.

  17. Vaccine-Induced Control of Viral Shedding following Rhesus Cytomegalovirus Challenge in Rhesus Macaques▿

    OpenAIRE

    Abel, Kristina; Martinez, Joy; Yue, Yujuan; Lacey, Simon F.; Wang, Zhongde; Strelow, Lisa; Dasgupta, Anindya; Li, Zhongqi; Schmidt, Kimberli A; Oxford, Kristie L.; Assaf, Basel; Longmate, Jeffrey A.; Diamond, Don J.; Barry, Peter A.

    2010-01-01

    The use of animal models of human cytomegalovirus (HCMV) infection is critical to refine HCMV vaccine candidates. Previous reports have demonstrated that immunization of rhesus monkeys against rhesus cytomegalovirus (RhCMV) can reduce both local and systemic replication of RhCMV following experimental RhCMV challenge. These studies used prime/boost combinations of DNA expression plasmids alone or DNA priming and boosting with either inactivated virion particles or modified vaccinia virus Anka...

  18. Rhesus factor modulation of effects of smoking and age on psychomotor performance, intelligence, personality profile, and health in Czech soldiers.

    Directory of Open Access Journals (Sweden)

    Jaroslav Flegr

    Full Text Available BACKGROUND: Rhesus-positive and rhesus-negative persons differ in the presence-absence of highly immunogenic RhD protein on the erythrocyte membrane. This protein is a component of NH(3 or CO(2 pump whose physiological role is unknown. Several recent studies have shown that RhD positivity protects against effects of latent toxoplasmosis on motor performance and personality. It is not known, however, whether the RhD phenotype modifies exclusively the response of the body to toxoplasmosis or whether it also influences effects of other factors. METHODOLOGY/PRINCIPAL FINDINGS: In the present cohort study, we searched for the effects of age and smoking on performance, intelligence, personality and self-estimated health and wellness in about 3800 draftees. We found that the positive effect of age on performance and intelligence was stronger in RhD-positive soldiers, while the negative effect of smoking on performance and intelligence was of similar size regardless of the RhD phenotype. The effect of age on four Cattell's personality factors, i.e., dominance (E, radicalism (Q(1, self-sentiment integration (Q(3, and ergic tension (Q(4, and on Cloninger's factor reward dependency (RD was stronger for RhD-negative than RhD-positive subjects, while the effect of smoking on the number of viral and bacterial diseases was about three times stronger for RhD-negative than RhD-positive subjects. CONCLUSIONS: RhD phenotype modulates the influence not only of latent toxoplasmosis, but also of at least two other potentially detrimental factors, age and smoking, on human behavior and physiology. The negative effect of smoking on health (estimated on the basis of the self-rated number of common viral and bacterial diseases in the past year was much stronger in RhD-negative than RhD-positive subjects. It is critically needed to confirm the differences in health response to smoking between RhD-positive and RhD-negative subjects by objective medical examination in

  19. High affinity dopamine D2 receptor radioligands. 3. [123I] and [125I]epidepride: In vivo studies in rhesus monkey brain and comparison with in vitro pharmacokinetics in rat brain

    International Nuclear Information System (INIS)

    Studies of [123I]epidepride uptake in rhesus monkey brain were performed using single photon tomography. Striatal uptake peaked at 0.85% of administered dose/g at 107 min post-injection, then declined slowly to 0.70% of administered dose/g at 6 h. Striatal:posterior brain ratios rose from 2 at 25 min to 6.8 at 105 min, to 15 at 4 h and to 58 at 6.4 h. [123I]Epidepride was displaced by haloperidol (0.1 and 1 mg/kg) with a half-life of washout of 55 min. Little displacement of [123I]epidepride was observed following administration of 1 or 2 mg/kg d-amphetamine, respectively, indicating [123I]epidepride is not easily displaced by endogenous dopamine. In vitro equilibrium binding studies with [125I]epidepride using rat striatum revealed a KD of 46 pM and Bmax of 33 pmol/g tissue at 37 degrees C, while at 25 degrees C the KD was 25 pM and the Bmax 32 pmol/g tissue. In vitro kinetic analysis of association and dissociation curves revealed a half-life for receptor dissociation at 37 degrees C of 15 min and 79--90 min at 25 degrees C. Allowing for the temperature difference, there is good correspondence between in vivo and in vitro dissociation kinetics at 25 degrees C. Increasing in vitro incubation temperature from 25 to 37 degrees C caused a 6-fold increase in the dissociation rate, suggesting that there is a change in binding kinetics at the dopamine D2 receptor at 37 degrees C compared to in vivo binding. The results of this study indicate that [123I]epidepride is an excellent radioligand for SPECT studies of the dopamine D2 receptor in man. 34 refs., 4 figs

  20. Amylase and blood cell-count hematological radiation-injury biomarkers in a rhesus monkey radiation model-use of multiparameter and integrated biological dosimetry

    International Nuclear Information System (INIS)

    Effective medical management of suspected radiation exposure incidents requires the recording of dynamic medical data (clinical signs and symptoms), biological assessments of radiation exposure, and physical dosimetry in order to provide diagnostic information to the treating physician and dose assessment for personnel radiation protection records. The need to rapidly assess radiation dose in mass-casualty and population-monitoring scenarios prompted an evaluation of suitable biomarkers that can provide early diagnostic information after exposure. We investigated the utility of serum amylase and hematological blood-cell count biomarkers to provide early assessment of severe radiation exposures in a non-human primate model (i.e., rhesus macaques; n=8) exposed to whole-body radiation of 60Co-gamma rays (6.5 Gy, 40cGymin-1). Serum amylase activity was significantly elevated (12.3±3.27- and 2.6±0.058-fold of day zero samples) at 1 and 2-days, respectively, after radiation. Lymphocyte cell counts decreased (≤15% of day zero samples) 1 and 2 days after radiation exposure. Neutrophil cell counts increased at day one by 1.9(±0.38)-fold compared with levels before irradiation. The ratios of neutrophil to lymphocyte cell counts increased by 13(±2.66)- and 4.23(±0.95)-fold at 1 and 2 days, respectively, after irradiation. These results demonstrate that increases in serum amylase activity along with decreases of lymphocyte counts, increases in neutrophil cell counts, and increases in the ratio of neutrophil to lymphocyte counts 1 day after irradiation can provide enhanced early triage discrimination of individuals with severe radiation exposure and injury. Use of the biodosimetry assessment tool (BAT) application is encouraged to permit dynamic recording of medical data in the management of a suspected radiological casualty

  1. A Reevaluation of the Question: Is the Pubertal Resurgence in Pulsatile GnRH Release in the Male Rhesus Monkey (Macaca mulatta) Associated With a Gonad-Independent Augmentation of GH Secretion?

    Science.gov (United States)

    Shahab, M; Trujillo, M Vargas; Plant, T M

    2015-10-01

    A somatic signal has been posited to trigger the pubertal resurgence in pulsatile GnRH secretion that initiates puberty in highly evolved primates. That GH might provide such a signal emerged in 2000 as a result of a study reporting that circulating nocturnal GH concentrations in castrated juvenile male monkeys increased in a 3-week period immediately preceding the pubertal resurgence of LH secretion. The present study was conducted to reexamine this intriguing relationship, again in an agonadal model. Four castrated juvenile male monkeys were implanted with indwelling jugular catheters, housed in remote sampling cages, and subjected to 24 hours of sequential blood sampling (every 30 min) every 2 weeks from 19.5 to 22 months of age. Twenty-four-hour profiles of circulating GH concentrations were analyzed using the pulse detection algorithm, PULSAR, and developmental changes in pulsatile GH release with respect to the initiation of the pubertal rise of LH secretion (week 0; observed between 22.5 and 32 mo of age) were examined for significance by a repeated-measures ANOVA. Changes in the parameters of pulsatile GH secretion, including mean 24-hour GH concentration and GH pulse frequency and pulse amplitude for 3 (n = 4) and 6 (n = 3) months before week 0 were unremarkable and nonsignificant. These findings fail to confirm those of the earlier study and lead us to conclude that the timing of the pubertal resurgence of GnRH release in the male monkey is not dictated by GH. Reasons for the discrepancy between the two studies are unclear. PMID:26181107

  2. Test and Analysis of Coagulation Time of Four Kinds of Coagulation Factors in Captive Bred Tree Shrew and Rhesus Monkey%人工饲养树鼩和猕猴的部分凝血因子凝集时间的测定及分析

    Institute of Scientific and Technical Information of China (English)

    黄璋琼; 代解杰; 孙晓梅; 李辛斌; 高家红

    2011-01-01

    Objective To test and analyze the coagulation time of four kinds of coagulation factors in healthy , captive bred tree shrew and rhesus monkey, and to establish the reference values range of coagulation factors values in the two animals. Methods Prothrombin time ( PT) , activated partial thromboplastin time ( APTT) , fibrinogen time ( FIB) , and thrombin time ( TT) of captive bred tree shrews and rhesus monkeys were tested by using the Sysmex CA-510 automated blood coagulation analyzer, then the data were analyzed in using the statistics analysis software SPSS vl7. 0. Results In Tree shrew and Rhesus monkey, TT was respectively 19. 27 s and 20. 81 s;PT was respectively 17.34 s and 9.82 s; FIB was respectively 30.51 s and 18.73s; APPT was respectively 27. 88 s and 33. 56 s. The differences in PT and FIB were highly significant(P <0. 01) between captive bred tree shrew and rhesus monkey;and the differences in TT and APTT were also statistical significant(P <0. 05) between the captive bred tree shrew and the rhesus monkey. Conclusion There were significant differences in coagulation time of the four kinds of coagulation factors between animals, but there had no differencees in the different gender of same species.%目的 目前有关人工饲养树鼩与猕猴部分凝血因子凝集时间的资料甚少,拟初步建立这两种动物部分凝血因子凝集时间的参考值范围.方法采用全自动血凝仪测定树鼩、猕猴的血浆凝血酶时间(TT)、纤维蛋白原(Fib)、活化部分凝血活酶时间(APTT)、凝血酶原时间(PT).结果树鼩的TT、PT、Fib和APTT值分别为19.27、17.34、30.51和27.88s.猕猴的TT、PT、Fib和APTT值分别为20.81、9.82、18.73和33.56 s.人工饲养树鼩与猕猴的PT值、Fib值存在显著性差异(P<0.01),APTT值、TT值存在差异(P<0.05).结论人工饲养树鼩和猕猴部分凝血因子的凝集时间存在一定差异,同一物种雌雄个体间部分凝血因子的凝集时间没有明显差异.

  3. Parvalbumin increases in the medial and lateral geniculate nuclei of aged rhesus macaques

    OpenAIRE

    Gray, Daniel T.; Engle, James R.; Recanzone, Gregg H.

    2013-01-01

    Subcortical auditory structures in the macaque auditory system increase their densities of neurons expressing the calcium binding protein parvalbumin (PV) with age. However, it is unknown whether these increases occur in the thalamic division of the auditory system, the medial geniculate nucleus (MGN). Furthermore, it is also unclear whether these age-related changes are specific to the macaque auditory system or are generalized to other sensory systems. To address these questions, the PV ...

  4. High affinity dopamine D2 receptor radioligands. 3. [[sup 123]I] and [[sup 125]I]epidepride: In vivo studies in rhesus monkey brain and comparison with in vitro pharmacokinetics in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, R.M.; Votaw, J.R.; Schmidt, D.E.; Ansari, M.S.; Holdeman, K.P.; Paulis, T. de; Clanton, J.A.; Pfeffer, R.; Manning, R.G.; Ebert, M.H. (Vanderbilt Univ., Nashville, TN (United States))

    1993-01-01

    Studies of [[sup 123]I]epidepride uptake in rhesus monkey brain were performed using single photon tomography. Striatal uptake peaked at 0.85% of administered dose/g at 107 min post-injection, then declined slowly to 0.70% of administered dose/g at 6 h. Striatal:posterior brain ratios rose from 2 at 25 min to 6.8 at 105 min, to 15 at 4 h and to 58 at 6.4 h. [[sup 123]I]Epidepride was displaced by haloperidol (0.1 and 1 mg/kg) with a half-life of washout of 55 min. Little displacement of [[sup 123]I]epidepride was observed following administration of 1 or 2 mg/kg d-amphetamine, respectively, indicating [[sup 123]I]epidepride is not easily displaced by endogenous dopamine. In vitro equilibrium binding studies with [[sup 125]I]epidepride using rat striatum revealed a K[sub D] of 46 pM and B[sub max] of 33 pmol/g tissue at 37[degrees]C, while at 25[degrees]C the K[sub D] was 25 pM and the B[sub max] 32 pmol/g tissue. In vitro kinetic analysis of association and dissociation curves revealed a half-life for receptor dissociation at 37[degrees]C of 15 min and 79--90 min at 25[degrees]C. Allowing for the temperature difference, there is good correspondence between in vivo and in vitro dissociation kinetics at 25[degrees]C. Increasing in vitro incubation temperature from 25 to 37[degrees]C caused a 6-fold increase in the dissociation rate, suggesting that there is a change in binding kinetics at the dopamine D2 receptor at 37[degrees]C compared to in vivo binding. The results of this study indicate that [[sup 123]I]epidepride is an excellent radioligand for SPECT studies of the dopamine D2 receptor in man. 34 refs., 4 figs.

  5. Electrophysiological study, biodistribution in mice, and preliminary PET evaluation in a rhesus monkey of 1-amino-3-[18F]fluoromethyl-5-methyl-adamantane (18F-MEM): a potential radioligand for mapping the NMDA-receptor complex

    International Nuclear Information System (INIS)

    The effect of the fluorinated memantine derivative and NMDA receptor antagonist, 1-amino-3-fluoromethyl-5-methyl-adamantane (19F-MEM), at the NMDA receptor ion channel was studied by patch clamp recording. The results showed that 19F-MEM is a moderate NMDA receptor channel blocker. A procedure for the routine preparation of the 18F-labelled analog 18F-MEM has been developed using a two-step reaction sequence. This involves the no-carrier-added nucleophilic radiofluorination of 1-[N-(tert-butyloxy)carbamoyl]-3-(toluenesulfonyloxy)methyl-5- methyl-adamantane and the subsequent cleavage of the BOC-protecting group using aqueous HCl. The 18F-MEM was obtained in 22±7% radiochemical yield (decay-corrected to EOB) in a total synthesis time including HPLC purification of 90 min. A biodistribution study after IV injection of 18F-MEM in mice showed a fast clearance of radioactivity from blood and relatively high initial uptake in the kidney and in the lung, which gradually decreased with time. The brain uptake was high (up to 3.6% ID/g, 60 min postinjection) with increasing brain-blood ratios: 2.40, 5.10, 6.33, and 9.27 at 5, 30, 60, and 120 min, respectively. The regional accumulation of the radioactivity in the mouse brain was consistent with the known distribution of the PCP recognition site. Preliminary PET evaluation of the radiotracer in a rhesus monkey demonstrated good uptake and prolonged retention in the brain, with a plateau from 35 min onwards p.i. in the NMDA receptor-rich regions (frontal cortex, striata, and temporal cortex). Delineation of the hippocampus, a region known to contain a high density of NMDA receptors, was not possible owing to the resolution of the PET tomograph. The regional brain uptake of 18F-MEM was changed by memantine and by a pharmacological dose of (+)-MK-801, indicating competition for the same binding sites. In a preliminary experiment, haloperidol, a dopamine D2 and sigma receptor antagonist, decreased the binding of 18F-MEM from the

  6. No effect of different estrogen receptor ligands on cognition in adult female monkeys.

    Science.gov (United States)

    Lacreuse, Agnès; Wilson, Mark E; Herndon, James G

    2009-03-01

    Many studies in women and animal models suggest that estrogens affect cognitive function. Yet, the mechanisms by which estrogens may impact cognition remain unclear. The goal of the present study was to assess the effects of different estrogen receptor (ER) ligands on cognitive function in adult ovariectomized female rhesus monkeys. The monkeys were tested for 6 weeks on a battery of memory and attentional tasks administered on a touchscreen: the object, face, and spatial versions of the Delayed Recognition Span Test (DRST) and a Visual Search task. Following a 2-week baseline period with oil vehicle treatment, monkeys were randomly assigned to one of 3 treatment groups: estradiol benzoate (EB), selective ERbeta agonist (diarylpropionitrile DPN) or selective ER modulator tamoxifen (TAM). In each treatment group, monkeys received oil vehicle for 2 weeks and the drug for 2 weeks, in a cross-over design. After a 4-week washout, a subset of monkeys was re-tested on the battery when treated with a selective ERalpha agonist (propyl-pyrazole-triol, PPT) or oil vehicle. Overall, drug treatments had no or negligible effects on cognitive performance. These results support the contention that exogenous estrogens and selective estrogen receptor modulators (SERMS) do not significantly affect cognition in young adult female macaques. Additional studies are needed to determine whether the cognitive effects of estrogens in monkeys of more advanced age are mediated by ERbeta, ERalpha or complex interactions between the two receptors. PMID:19101578

  7. Crossmodal Integration of Conspecific Vocalizations in Rhesus Macaques

    OpenAIRE

    Payne, Christa; Bachevalier, Jocelyne

    2013-01-01

    Crossmodal integration of audio/visual information is vital for recognition, interpretation and appropriate reaction to social signals. Here we examined how rhesus macaques process bimodal species-specific vocalizations by eye tracking, using an unconstrained preferential looking paradigm. Six adult rhesus monkeys (3M, 3F) were presented two side-by-side videos of unknown male conspecifics emitting different vocalizations, accompanied by the audio signal corresponding to one of the videos. Th...

  8. Breeding monkeys for biomedical research

    Science.gov (United States)

    Bourne, G. H.; Golarzdebourne, M. N.; Keeling, M. E.

    1973-01-01

    Captive bred rhesus monkeys show much less pathology than wild born animals. The monkeys may be bred in cages or in an outdoor compound. Cage bred animals are not psychologically normal which makes then unsuited for some types of space related research. Compound breeding provides contact between mother and infant and an opportunity for the infants to play with their peers which are important requirements to help maintain their behavioral integrity. Offspring harvested after a year in the compound appear behaviorally normal and show little histopathology. Compound breeding is also an economical method for the rapid production of young animals. The colony can double its size about every two and a half years.

  9. Infectious Agent and Immune Response Characteristics of Chronic Enterocolitis in Captive Rhesus Macaques

    OpenAIRE

    Sestak, Karol; Merritt, Christopher K.; Borda, Juan; Saylor, Elizabeth; Schwamberger, Shelle R.; Cogswell, Frank; Didier, Elizabeth S; Didier, Peter J.; Plauche, Gail; Bohm, Rudolf P.; Aye, Pyone P.; Alexa, Pavel; Ward, Richard L.; Lackner, Andrew A

    2003-01-01

    Chronic enterocolitis is the leading cause of morbidity in colonies of captive rhesus macaques (Macaca mulatta). This study's aim was to identify the common enteric pathogens frequently associated with chronic enterocolitis in normal, immunocompetent rhesus monkeys and to elucidate the influence of this clinical syndrome on the host immune system. We analyzed the fecal specimens from 100 rhesus macaques with or without clinical symptoms of chronic diarrhea. Retrospective analysis revealed an ...

  10. Comprehensive Analysis of Rhesus Lymphocryptovirus MicroRNA Expression▿ †

    OpenAIRE

    Riley, Kasandra J.-L.; Rabinowitz, Gabrielle S.; Steitz, Joan A.

    2010-01-01

    Rhesus lymphocryptovirus (rLCV) and Epstein-Barr virus (EBV) are closely related gammaherpesviruses that infect and cause disease in rhesus monkeys and humans, respectively. Thus, rLCV is an important model system for EBV pathogenesis. Both rLCV and EBV express microRNAs (miRNAs), several conserved in sequence and genomic location. We have applied deep sequencing technology to obtain an inventory of rLCV miRNA expression in latently rLCV-infected monkey B cells. Our data confirm the presence ...

  11. Vicarious Reinforcement in Rhesus Macaques (Macaca Mulatta)

    OpenAIRE

    Chang, Steve W. C.; Amy A. Winecoff; Platt, Michael L.

    2011-01-01

    What happens to others profoundly influences our own behavior. Such other-regarding outcomes can drive observational learning, as well as motivate cooperation, charity, empathy, and even spite. Vicarious reinforcement may serve as one of the critical mechanisms mediating the influence of other-regarding outcomes on behavior and decision-making in groups. Here we show that rhesus macaques spontaneously derive vicarious reinforcement from observing rewards given to another monkey, and that this...

  12. Vicarious Reinforcement In Rhesus Macaques (Macaca mulatta)

    OpenAIRE

    Chang, Steve W. C.; Amy A. Winecoff; Platt, Michael L.

    2011-01-01

    What happens to others profoundly influences our own behavior. Such other-regarding outcomes can drive observational learning, as well as motivate cooperation, charity, empathy, and even spite. Vicarious reinforcement may serve as one of the critical mechanisms mediating the influence of other-regarding outcomes on behavior and decision-making in groups. Here we show that rhesus macaques spontaneously derive vicarious reinforcement from observing rewards given to another monkey, and that t...

  13. Nuclear weapon testing and the monkey business

    International Nuclear Information System (INIS)

    Reasons for India's total ban on the export of rhesus monkeys to U.S. have been explained. The major reason is that some of the animals were used in nuclear weapon related radiation experiments. This was a clear violation of a stricture in the agreement about supply of monkeys. The stricture prohibited the use of animals for research concerning military operations, including nuclear weapon testing. It is pleaded that a strict enforcement of strictures rather than a total ban on the export of monkeys would be better in the interest of advancement of knowledge in human medicine and disease control. (M.G.B.)

  14. Laparoscopic diagnosis of gross reproductive abnormalities in free-ranging female rhesus macaques (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Vijay Kumar

    2012-11-01

    Full Text Available A study was conducted between July 2010 to June 2011 in the Monkey Sterilization Centre, Gopalpur, Himachal Pradesh, India to assess the prevalence of reproductive disorders by laparoscopic examination of the genitalia of female rhesus macaques. The animals were captured from different locations in the state using a cage trapping method. A total of 720 female rhesus macaques underwent laparoscopic examination of their reproductive tracts. A total of 63 cases were found to have reproductive abnormalities. Out of these 63 cases, the most common abnormalities reported were ovarian cyst 3.05% (n=22, ovarian tumor 1.66% (n=12, uterine tumor 1.25% (n=9, uterine edema 0.97% (n=7, uterine rupture 0.83% (n=6, ectopic pregnancy 0.69% (n=5, unicornis or acornis 0.28% (n=2. The highest number of cases of uterine abnormalities was recorded in the 12-16 year old age group (33.33%, followed by 8-12 year olds (25.39%, 16-20 year olds (22.22%, then 4-8 year olds (15.87% and 0-4 year olds (3.17%. Of the 63 animals that showed genital abnormalities, only 52 were found to be pregnant during the breeding season from November to March in the 5-20 year old age group, while 11 animals were not pregnant; a pregnancy rate of 82.53% (52 of 63 of the female rhesus macaques with reproductive abnormalities.

  15. The elusive illusion: Do children (Homo sapiens) and capuchin monkeys (Cebus apella) see the Solitaire illusion?

    Science.gov (United States)

    Parrish, Audrey E; Agrillo, Christian; Perdue, Bonnie M; Beran, Michael J

    2016-02-01

    One approach to gaining a better understanding of how we perceive the world is to assess the errors that human and nonhuman animals make in perceptual processing. Developmental and comparative perspectives can contribute to identifying the mechanisms that underlie systematic perceptual errors often referred to as perceptual illusions. In the visual domain, some illusions appear to remain constant across the lifespan, whereas others change with age. From a comparative perspective, many of the illusions observed in humans appear to be shared with nonhuman primates. Numerosity illusions are a subset of visual illusions and occur when the spatial arrangement of stimuli within a set influences the perception of quantity. Previous research has found one such illusion that readily occurs in human adults, the Solitaire illusion. This illusion appears to be less robust in two monkey species, rhesus macaques and capuch