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Sample records for pregnant rhesus monkeys

  1. Pharmacokinetics of cocaine in pregnant and nonpregnant rhesus monkeys.

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    Duhart, H M; Fogle, C M; Gillam, M P; Bailey, J R; Slikker, W; Paule, M G

    1993-01-01

    To determine pharmacokinetic parameters for cocaine in rhesus monkey plasma, samples were taken over several hours after i.m. administration of cocaine plus a tritiated cocaine tracer. Cocaine and its metabolites, benzoylecgonine and norcocaine, were isolated via HPLC and quantitated using liquid scintillation spectrometry. Pregnant subjects were dosed with cocaine at 0.3 (n = 3) or 1.0 (n = 3) mg/kg, whereas nonpregnant female subjects were dosed with 1.0 mg/kg (n = 3). For the pregnant subjects, pharmacokinetic studies were conducted on about gestational day 125 and areas under the concentration versus time curve (AUCs, ng/mL x h) were 64 +/- 26 (+/- SEM) and 143 +/- 12; half-lives (t1/2s, h) were 1.9 +/- 0.6 and 1.1 +/- 0.1 after 0.3 and 1.0 mg/kg i.m., respectively. For nonpregnant subjects dosed acutely with 1.0 mg/kg, the AUC was 262 +/- 63 and the t1/2 was 1.4 +/- 0.3. There appear to be few differences in the pharmacokinetic parameters of cocaine and benzoylecgonine between pregnant and nonpregnant monkeys in this study.

  2. Effect of prolonged ketamine exposure on cardiovascular physiology in pregnant and infant rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Hotchkiss, Charlotte E; Wang, Cheng; Slikker, William

    2007-11-01

    Physiologic measurements in nonhuman primates usually are collected from animals that are chemically or physically restrained. Both types of restraint may affect the parameters measured, and those effects can vary with age. Heart rate, respiratory rate, oxygen saturation, expired CO2, blood pressure, temperature, blood glucose, hematocrit, and venous blood gasses were measured in rhesus monkeys that were either infused intravenously with ketamine for 24 h or were cage-housed and physically restrained for sample collection. The subjects were pregnant monkeys at gestational day 120 to 123, infants 5 to 6 d old, and infants 35 to 37 d old. Heart rate and blood pressure were lower in ketamine-treated monkeys than physically restrained monkeys. Heart rate was higher in infants than adults, whereas blood pressure was lower in infants. Respiratory rate was higher in infants than adults and higher in physically restrained infants than ketamine-sedated infants but was not affected by ketamine in pregnant adults. Hematocrit was decreased in older infants. In summary, both physical restraint and ketamine sedation altered several physiologic parameters in pregnant and infant rhesus macaques. Investigators should consider these effects when designing experiments and evaluating experimental outcomes in monkeys.

  3. Artificial Nursing Procedure Establishment for Infant Rhesus Monkeys

    Institute of Scientific and Technical Information of China (English)

    Wang Hong; Si Wei; Zhou Yin; Chen Lixian

    2015-01-01

    Rhesus monkey can not achieve natural delivery due to various reasons,and cesarean section becomes an important midwifery to get infant monkeys. After caesarean section,the pregnant monkey is weak and postoperative wound pain,so it can not personally feed infant monkeys which must be artificially fed. Thus,establishing suitable feeding management program is very important for improving survival rate of infant rhesus monkey and maintaining good health. We summarized food preparation method for infant rhesus monkeys as well as temperature setting and light control,and established the nursing program for newborn infant monkey and daily management process for infant monkeys.

  4. HTRA3 expression in non-pregnant rhesus monkey ovary and endometrium, and at the maternal-fetal interface during early pregnancy

    Directory of Open Access Journals (Sweden)

    Findlay Jock K

    2008-06-01

    Full Text Available Abstract Background HTRA3 is a recently identified member of the mammalian serine protease family HTRA (high temperature requirement factor A. In both the rodent and the human HTRA3 is transcribed into two mRNA species (long and short through alternative splicing. We have previously shown that HTRA3 is expressed in the mature rat ovary and may be involved in folliculogenesis and luteinisation. HTRA3 is also upregulated during mouse and human placental development. The current study investigated whether HTRA3 is also localised in the primate ovary (rhesus monkey n = 7. In addition, we examined the non-pregnant rhesus monkey endometrium (n = 4 and maternal-fetal interface during early pregnancy (n = 5 to further investigate expression of HTRA3 in primate endometrium and placentation. Methods HTRA3 mRNA levels in several rhesus monkey tissues was determined by semiquantitative RT-PCR. Protein expression and localisation of HTRA3 was determined by immunohistochemistry. Results Long and short forms of HTRA3 mRNA were detected in the ovary, aorta, bladder, small intestine, skeletal muscle, heart and uterus but not the liver nor the kidney. HTRA3 protein was immunolocalised to the oocyte of all follicular stages in the rhesus monkey ovary. Protein expression in mural and cumulus granulosa cells of late secondary follicles increased significantly compared to granulosa cells of primordial, primary and secondary follicles. Mural and cumulus granulosa cells of antral follicles also showed a significant increase in expression. Staining intensity was higher in the granulosa-lutein cells compared to the theca-lutein cells of corpora lutea (n = 3. In the non-pregnant monkey endometrium, HTRA3 was detected in the glandular epithelium. The basalis endometrial glands showed higher staining intensity than functionalis endometrial glands. During early pregnancy, strong staining for HTRA3 protein was seen in both maternal decidual cells and glands. Conclusion We

  5. Spontaneous Metacognition in Rhesus Monkeys.

    Science.gov (United States)

    Rosati, Alexandra G; Santos, Laurie R

    2016-09-01

    Metacognition is the ability to think about thinking. Although monitoring and controlling one's knowledge is a key feature of human cognition, its evolutionary origins are debated. In the current study, we examined whether rhesus monkeys (Macaca mulatta; N = 120) could make metacognitive inferences in a one-shot decision. Each monkey experienced one of four conditions, observing a human appearing to hide a food reward in an apparatus consisting of either one or two tubes. The monkeys tended to search the correct location when they observed this baiting event, but engaged in information seeking-by peering into a center location where they could check both potential hiding spots-if their view had been occluded and information seeking was possible. The monkeys only occasionally approached the center when information seeking was not possible. These results show that monkeys spontaneously use information about their own knowledge states to solve naturalistic foraging problems, and thus provide the first evidence that nonhumans exhibit information-seeking responses in situations with which they have no prior experience.

  6. Rhesus monkey heart rate during exercise

    Science.gov (United States)

    Delorge, J.; Thach, J. S., Jr.

    1972-01-01

    Various schedules of reinforcement and their relation to heart rates of rhesus monkeys during exercise are described. All the reinforcement schedules produced 100 per cent or higher increments in the heart rates of the monkeys during exercise. Resting heart rates were generally much lower than those previously reported, which was attributed to the lack of physical restraint of the monkeys during recording.

  7. Generation of chimeric rhesus monkeys.

    Science.gov (United States)

    Tachibana, Masahito; Sparman, Michelle; Ramsey, Cathy; Ma, Hong; Lee, Hyo-Sang; Penedo, Maria Cecilia T; Mitalipov, Shoukhrat

    2012-01-20

    Totipotent cells in early embryos are progenitors of all stem cells and are capable of developing into a whole organism, including extraembryonic tissues such as placenta. Pluripotent cells in the inner cell mass (ICM) are the descendants of totipotent cells and can differentiate into any cell type of a body except extraembryonic tissues. The ability to contribute to chimeric animals upon reintroduction into host embryos is the key feature of murine totipotent and pluripotent cells. Here, we demonstrate that rhesus monkey embryonic stem cells (ESCs) and isolated ICMs fail to incorporate into host embryos and develop into chimeras. However, chimeric offspring were produced following aggregation of totipotent cells of the four-cell embryos. These results provide insights into the species-specific nature of primate embryos and suggest that a chimera assay using pluripotent cells may not be feasible.

  8. Vitreal syneresis in rhesus monkeys.

    Science.gov (United States)

    Stuck, B E; Talsma, D M; Beatrice, E S

    1977-11-01

    The eyes of 15 rhesus monkeys were evaluated. Various degrees of vitreal syneresis were observed in 28 of the 30 eyes. The observed vitreal structures varied from fine strands randomly spaced throughout the vitreous to thick, intertwining, fibrous networks with some clumping of the collagenous condensate at the fiber junctions. Qualitatively, the degree of syneresis was slightly more extensive in the eight older mature males than in the seven younger animals. In all animals a clear view of the fundus could be obtained with the ophthalmoscope. The vitreous structures may be one cause of variability in ocular dose-response relationships for exposure to laser radiation. The effect on retinal exposure experiments of the finer vitreal structure is considered minimal.

  9. 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 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

  10. Canine distemper outbreak in rhesus monkeys, China.

    Science.gov (United States)

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

    2011-08-01

    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.

  11. The Effect of Heterogeneity on Numerical Ordering in Rhesus Monkeys

    Science.gov (United States)

    Cantlon, Jessica F.; Brannon, Elizabeth M.

    2006-01-01

    We investigated how within-stimulus heterogeneity affects the ability of rhesus monkeys to order pairs of the numerosities 1 through 9. Two rhesus monkeys were tested in a touch screen task where the variability of elements within each visual array was systematically varied by allowing elements to vary in color, size, shape, or any combination of…

  12. Spaceflight and Immune Responses of Rhesus Monkeys

    Science.gov (United States)

    Sonnenfeld, Gerald

    1997-01-01

    In the grant period, we perfected techniques for determination of interleukin production and leukocyte subset analysis of rhesus monkeys. These results are outlined in detail in publication number 2, appended to this report. Additionally, we participated in the ARRT restraint test to determine if restraint conditions for flight in the Space Shuttle could contribute to any effects of space flight on immune responses. All immunological parameters listed in the methods section were tested. Evaluation of the data suggests that the restraint conditions had minimal effects on the results observed, but handling of the monkeys could have had some effect. These results are outlined in detail in manuscript number 3, appended to this report. Additionally, to help us develop our rhesus monkey immunology studies, we carried out preliminary studies in mice to determine the effects of stressors on immunological parameters. We were able to show that there were gender-based differences in the response of immunological parameters to a stressor. These results are outlined in detail in manuscript number 4, appended to this report.

  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. Transcriptional profiling of rhesus monkey embryonic stem cells.

    Science.gov (United States)

    Byrne, James A; Mitalipov, Shoukhrat M; Clepper, Lisa; Wolf, Don P

    2006-12-01

    Embryonic stem cells (ESCs) may be able to cure or alleviate the symptoms of various degenerative diseases. However, unresolved issues regarding survival, functionality, and tumor formation mean a prudent approach should be adopted towards advancing ESCs into human clinical trials. The rhesus monkey provides an ideal model organism for developing strategies to prevent immune rejection and test the feasibility, safety, and efficacy of ESC-based medical treatments. Transcriptional profiling of rhesus monkey ESCs provides a foundation for pre-clinical ESC research in this species. In the present study, we used microarray technology, immunocytochemistry, reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time PCR (qPCR) to characterize and transcriptionally profile rhesus monkey ESCs. We identified 367 stemness gene candidates that were highly (>85%) conserved across five different ESC lines. Rhesus monkey ESC lines maintained a pluripotent undifferentiated state over a wide range of POU5F1 (also known as OCT4) expression levels, and comparisons between rhesus monkey, mouse, and human stemness genes revealed five mammalian stemness genes: CCNB1, GDF3, LEFTB, POU5F1, and NANOG. These five mammalian genes are strongly expressed in rhesus monkey, mouse, and human ESCs, albeit only in the undifferentiated state, and represent the core key mammalian stemness factors.

  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. Protein composition of rhesus monkey milk: comparison to human milk.

    Science.gov (United States)

    Kunz, C; Lönnerdal, B

    1993-04-01

    1. Proteins in human milk and Rhesus monkey milk have been compared by FPLC gel filtration and anion exchange chromatography, SDS-Polyacrylamide gel electrophoresis, nitrogen and protein determination. 2. Mature Rhesus milk is higher in protein concentration (15-20 mg/ml) than human milk (8-9 mg/ml). 3. Non-Protein nitrogen is 6-13% in Rhesus milk but 25-30% in human milk. 4. Secretory IgA, lactoferrin, serum albumin, alpha-lactalbumin and lysozyme are present in Rhesus milk, but at a lower concentration than in human milk. 5. The casein subunit pattern is more complex in Rhesus milk compared to human milk. 6. The ratio of whey proteins to casein is similar in both milks (approximately 60/40). 7. A protein with a M(r) of 21,600 is a major component in monkey whey but is not found in human milk.

  17. Color-detection thresholds in rhesus macaque monkeys and humans

    OpenAIRE

    Gagin, Galina; Bohon, Kaitlin S.; Butensky, Adam; Gates, Monica A.; Hu, Jiun-Yiing; Lafer-Sousa, Rosa; Pulumo, Reitumetse L.; Qu, Jane; Stoughton, Cleo M.; Swanbeck, Sonja N.; Conway, Bevil R.

    2014-01-01

    Macaque monkeys are a model of human color vision. To facilitate linking physiology in monkeys with psychophysics in humans, we directly compared color-detection thresholds in humans and rhesus monkeys. Colors were defined by an equiluminant plane of cone-opponent color space. All subjects were tested on an identical apparatus with a four-alternative forced-choice task. Targets were 2° square, centered 2° from fixation, embedded in luminance noise. Across all subjects, the change in detection...

  18. Effects of feeding selenium deficient diets to rhesus monkeys (Macaca Mulatta)

    Energy Technology Data Exchange (ETDEWEB)

    Butler, J.A.; Whanger, P.D.; Patton, N.M.

    1988-02-01

    Pregnant rhesus monkeys (Macaca mulatta) were fed either selenium (Se) deficient or Se supplemented diets with adequate vitamin E. Except for some cardiac irregularities in the first babies born to these females, no physiological disorders due to Se deficiency were seen in a subsequent offspring. Plasma and erythrocyte glutathione peroxidase activities and blood Se levels increased in the Se supplemented monkeys but decreased in the deficient ones. The data indicated that hair Se levels reflect long term exposure to this element. In a very preliminary experiment, evidence was obtained to indicate that dietary protein deficiency along with Se deficiency will generate cardiomyopathic lesions characteristic of Se deficiency. It is hypothesized that, in addition to Se deficiency, another dietary deficiency (or abnormality) is necessary to produce Se deficiency lesions in higher primates. Higher glutathione transferase (or non-Se glutathione peroxidase) activity in tissues of rhesus monkeys may account for this resistance.

  19. Behavioral consequences of developmental iron deficiency in infant rhesus monkeys

    Science.gov (United States)

    Golub, Mari S.; Hogrefe, Casey E.; Germann, Stacey L.; Capitanio, John P.; Lozoff, Betsy

    2006-01-01

    Human studies have shown that iron deficiency and iron deficiency anemia in infants are associated with behavioral impairment, but the periods of brain development most susceptible to iron deficiency have not been established. In the present study, rhesus monkeys were deprived of iron by dietary iron restriction during prenatal (n = 14, 10 μg Fe/g diet) or early postnatal (n = 12, 1.5 mg Fe/L formula) brain development and compared to controls (n = 12, 100 μg Fe/g diet, 12 mg Fe/L formula) in behavioral evaluations conducted during the first four months of life in the nonhuman primate nursery. Iron deficiency anemia was detected in the pregnant dams in the third trimester and compromised iron status was seen in the prenatally iron-deprived infants at birth, but no iron deficiency was seen in either the prenatally or postnatally iron-deprived infants during the period of behavioral evaluation. Neither prenatal nor postnatal iron deprivation led to significant delays in growth, or gross or fine motor development. Prenatally deprived infants demonstrated a 20% reduced spontaneous activity level, lower inhibitory response to novel environments, and more changes from one behavior to another in weekly observation sessions. Postnatally deprived infants demonstrated poorer performance of an object concept task, and greater emotionality relative to controls. This study indicates that different syndromes of behavioral effects are associated with prenatal and postnatal iron deprivation in rhesus monkey infants and that these effects can occur in the absence of concurrent iron deficiency as reflected in hematological measures. PMID:16343844

  20. 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.

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

    Science.gov (United States)

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

    2014-12-01

    Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology 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 flow 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 flow was restored. A reversible middle cerebral artery occlusion model was identified 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 symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings 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 field of brain injury research.

  2. MAC of xenon and halothane in rhesus monkeys.

    Science.gov (United States)

    Whitehurst, S L; Nemoto, E M; Yao, L; Yonas, H

    1994-10-01

    Local cerebral blood flow (LCBF) maps produced by 33% xenon-enhanced computed tomographic scanning (Xe/CT LCBF) are useful in the clinical diagnosis and management of patients with cerebrovascular disorders. However, observations in humans that 25-35% xenon (Xe) inhalation increases cerebral blood flow (CBF) have raised concerns that Xe/CT LCBF measurements may be inaccurate and that Xe inhalation may be hazardous in patients with decreased intracranial compliance. In contrast, 33% Xe does not increase CBF in rhesus monkeys. To determine whether this interspecies difference in the effect of Xe on CBF correlates with an interspecies difference in the anesthetic potency of Xe, we measured the minimum alveolar concentration (MAC) of Xe preventing movement to a tail-clamp stimulus in rhesus monkeys. Using a standard protocol for the determination of MAC in animals, we first measured the MAC of halothane (n = 5), and then used a combination of halothane and Xe to measure the MAC of Xe (n = 7). The halothane MAC was 0.99 +/- 0.12% (M +/- SD), and the Xe MAC was 98 +/- 15%. These results suggest that the MAC of Xe in rhesus monkeys is higher than the reported human Xe MAC value of 71%. Thus the absence of an effect of 33% Xe on CBF in the rhesus monkey may be related to its lower anesthetic potency.

  3. Assessing Unit-Price Related Remifentanil Choice in Rhesus Monkeys

    Science.gov (United States)

    Galuska, Chad M.; Winger, Gail; Woods, James H.; Hursh, Steven R.

    2006-01-01

    Given a commodity available at different prices, a unit-price account of choice predicts preference for the cheaper alternative. This experiment determined if rhesus monkeys preferred remifentanil (an ultra-short-acting [mu]-opioid agonist) delivered at a lower unit price over a higher-priced remifentanil alternative (Phases 1 and 3). Choice…

  4. Evaluation of seven hypotheses for metamemory performance in rhesus monkeys.

    Science.gov (United States)

    Basile, Benjamin M; Schroeder, Gabriel R; Brown, Emily Kathryn; Templer, Victoria L; Hampton, Robert R

    2015-02-01

    Knowing the extent to which nonhumans and humans share mechanisms for metacognition will advance our understanding of cognitive evolution and will improve selection of model systems for biomedical research. Some nonhuman species avoid difficult cognitive tests, seek information when ignorant, or otherwise behave in ways consistent with metacognition. There is agreement that some nonhuman animals "succeed" in these metacognitive tasks, but little consensus about the cognitive mechanisms underlying performance. In one paradigm, rhesus monkeys visually searched for hidden food when ignorant of the location of the food, but acted immediately when knowledgeable. This result has been interpreted as evidence that monkeys introspectively monitored their memory to adaptively control information seeking. However, convincing alternative hypotheses have been advanced that might also account for the adaptive pattern of visual searching. We evaluated seven hypotheses using a computerized task in which monkeys chose either to take memory tests immediately or to see the answer again before proceeding to the test. We found no evidence to support the hypotheses of behavioral cue association, rote response learning, expectancy violation, response competition, generalized search strategy, or postural mediation. In contrast, we repeatedly found evidence to support the memory monitoring hypothesis. Monkeys chose to see the answer when memory was poor, either from natural variation or experimental manipulation. We found limited evidence that monkeys also monitored the fluency of memory access. Overall, the evidence indicates that rhesus monkeys can use memory strength as a discriminative cue for information seeking, consistent with introspective monitoring of explicit memory.

  5. Rhesus monkey brain imaging through intact skull with thermoacoustic tomography

    OpenAIRE

    Xu, Yuan; Wang, Lihong V.

    2006-01-01

    Two-dimensional microwave-induced thermoacoustic tomography (TAT) is applied to imaging the Rhesus monkey brain through the intact skull. To reduce the wavefront distortion caused by the skull, only the low-frequency components of the thermoacoustic signals (< 1 MHz) are used to reconstruct the TAT images. The methods of signal processing and image reconstruction are validated by imaging a lamb kidney. The resolution of the system is found to be 4 mm when we image a 1-month-old monkey head co...

  6. Rhesus monkeys (Macaca mulatta) map number onto space

    OpenAIRE

    Drucker, Caroline B.; Brannon, Elizabeth M.

    2014-01-01

    Humans map number onto space. However, the origins of this association, and particularly the degree to which it depends upon cultural experience, are not fully understood. Here we provide the first demonstration of a number-space mapping in a non-human primate. We trained four adult male rhesus macaques (Macaca mulatta) to select the fourth position from the bottom of a five-element vertical array. Monkeys maintained a preference to choose the fourth position through changes in the appearance...

  7. Mononeuropathy multiplex in rhesus monkeys with chronic Lyme disease.

    Science.gov (United States)

    England, J D; Bohm, R P; Roberts, E D; Philipp, M T

    1997-03-01

    Peripheral neuropathy is a recognized but poorly understood manifestation of Lyme disease. We performed serial electrophysiological studies on 8 rhesus monkeys chronically infected with the JD1 strain of Borrelia burgdorferi and compared the results with those of similar studies on 10 uninfected control monkeys. Four infected and 2 uninfected animals underwent sural nerve biopsy. Five of the infected and 1 of the uninfected animals also had postmortem neuropathological examinations. Altogether, 5 of the infected monkeys demonstrated primarily axonal-loss-variety multifocal neuropathies. Only one nerve lesion exhibited findings compatible with demyelination. Pathologically, peripheral nerve specimens showed multifocal axonal degeneration and regeneration and occasional perivascular inflammatory cellular infiltrates without vessel wall necrosis. Free spirochetal structures were not seen, but several macrophages exhibited positive immunostaining with a highly specific anti-B. burgdorferi, 7.5-kd lipoprotein monoclonal antibody. In the infected animals, serial analysis of serum antibodies to B. burgdorferi showed increasing numbers of IgG specificities and new IgM specificities, suggesting persistent infection. Thus, peripheral neuropathy in the form of a mononeuropathy multiplex develops frequently in rhesus monkeys chronically infected with B. burgdorferi. The pathogenesis of these nerve lesions is not yet known, but our studies suggest an immune-mediated process perhaps driven by persistent infection with B. burgdorferi.

  8. Rhesus monkey brain imaging through intact skull with thermoacoustic tomography.

    Science.gov (United States)

    Xu, Yuan; Wang, Lihong V

    2006-03-01

    Two-dimensional microwave-induced thermoacoustic tomography (TAT) is applied to imaging the Rhesus monkey brain through the intact skull. To reduce the wavefront distortion caused by the skull, only the low-frequency components of the thermoacoustic signals (images. The methods of signal processing and image reconstruction are validated by imaging a lamb kidney. The resolution of the system is found to be 4 mm when we image a 1-month-old monkey head containing inserted needles. We also image the coronal and axial sections of a 7-month-old monkey head. Brain features that are 3 cm deep in the head are imaged clearly. Our results demonstrate that TAT has potential for use in portable, cost-effective imagers for pediatric brains.

  9. Intrapericardial Denervation: Responses to Water Immersion in Rhesus Monkeys

    Science.gov (United States)

    McKeever, Kenneth H.; Keil, Lanny C.; Sandler, Harold

    1995-01-01

    Eleven anesthetized rhesus monkeys were used to study cardiovascular, renal, and endocrine alterations associated with 120 min of head-out water immersion. Five animals underwent complete intrapericardial denervation using the Randall technique, while the remaining six monkeys served as intact controls. Each animal was chronically instrumented with an electromagnetic flow probe on the ascending aorta, a strain gauge pressure transducer implanted in the apex of the left ventricle (LV), and electrocardiogram leads anchored to the chest wall and LV. During immersion, LV end-diastolic pressure, urine flow, glomerular filtration rate, sodium excretion, and circulating atrial natriuretic peptide (ANP) each increased (P less than 0.05) for intact and denervated monkeys. There were no alterations in free water clearance in either group during immersion, yet fractional excretion of free water increased (P less than 0.05) in the intact monkeys. Plasma renin activity (PRA) decreased (P less than 0.05) during immersion in intact monkeys but not the denervated animals. Plasma vasopressin (PVP) concentration decreased (P less than 0.05) during the first 30 min of immersion in both groups but was not distinguishable from control by 60 min of immersion in denervated monkeys. These data demonstrate that complete cardiac denervation does not block the rise in plasma ANP or prevent the natriuresis associated with head-out water immersion. The suppression of PVP during the first minutes of immersion after complete cardiac denervation suggests that extracardiac sensing mechanisms associated with the induced fluid shifts may be responsible for the findings.

  10. Color-detection thresholds in rhesus macaque monkeys and humans.

    Science.gov (United States)

    Gagin, Galina; Bohon, Kaitlin S; Butensky, Adam; Gates, Monica A; Hu, Jiun-Yiing; Lafer-Sousa, Rosa; Pulumo, Reitumetse L; Qu, Jane; Stoughton, Cleo M; Swanbeck, Sonja N; Conway, Bevil R

    2014-07-15

    Macaque monkeys are a model of human color vision. To facilitate linking physiology in monkeys with psychophysics in humans, we directly compared color-detection thresholds in humans and rhesus monkeys. Colors were defined by an equiluminant plane of cone-opponent color space. All subjects were tested on an identical apparatus with a four-alternative forced-choice task. Targets were 2° square, centered 2° from fixation, embedded in luminance noise. Across all subjects, the change in detection thresholds from initial testing to plateau performance (“learning”) was similar for +L − M (red) colors and +M − L (bluish-green) colors. But the extent of learning was higher for +S (lavender) than for −S (yellow-lime); moreover, at plateau performance, the cone contrast at the detection threshold was higher for +S than for −S. These asymmetries may reflect differences in retinal circuitry for S-ON and S-OFF. At plateau performance, the two species also had similar detection thresholds for all colors, although monkeys had shorter reaction times than humans and slightly lower thresholds for colors that modulated L/M cones. We discuss whether these observations, together with previous work showing that monkeys have lower spatial acuity than humans, could be accounted for by selective pressures driving higher chromatic sensitivity at the cost of spatial acuity amongst monkeys, specifically for the more recently evolved L − M mechanism.

  11. Effects of Head-down Tilt on Nerve Conduction in Rhesus Monkeys

    Directory of Open Access Journals (Sweden)

    Bo Sun

    2017-01-01

    Conclusions: This study demonstrates that the compound muscle action potential amplitudes of nerves are decreased under simulated microgravity in rhesus monkeys. Moreover, rhesus monkeys exposed to HDT might be served as an experimental model for the study of NCS under microgravity.

  12. Rhesus monkeys (Macaca mulatta) map number onto space.

    Science.gov (United States)

    Drucker, Caroline B; Brannon, Elizabeth M

    2014-07-01

    Humans map number onto space. However, the origins of this association, and particularly the degree to which it depends upon cultural experience, are not fully understood. Here we provide the first demonstration of a number-space mapping in a non-human primate. We trained four adult male rhesus macaques (Macaca mulatta) to select the fourth position from the bottom of a five-element vertical array. Monkeys maintained a preference to choose the fourth position through changes in the appearance, location, and spacing of the vertical array. We next asked whether monkeys show a spatially-oriented number mapping by testing their responses to the same five-element stimulus array rotated ninety degrees into a horizontal line. In these horizontal probe trials, monkeys preferentially selected the fourth position from the left, but not the fourth position from the right. Our results indicate that rhesus macaques map number onto space, suggesting that the association between number and space in human cognition is not purely a result of cultural experience and instead has deep evolutionary roots.

  13. 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.

  14. Immunization with Recombinant Helicobacter pylori Urease in Specific-Pathogen-Free Rhesus Monkeys (Macaca mulatta)

    OpenAIRE

    Solnick, Jay V.; Canfield, Don R.; Hansen, Lori M.; Torabian, Sima Z.

    2000-01-01

    Immunization with urease can protect mice from challenge with Helicobacter pylori, though results vary depending on the particular vaccine, challenge strain, and method of evaluation. Unlike mice, rhesus monkeys are naturally colonized with H. pylori and so may provide a better estimate of vaccine efficacy in humans. The purpose of this study was to examine the effectiveness of H. pylori urease as a vaccine in specific-pathogen (H. pylori)-free rhesus monkeys. Monkeys raised from birth and do...

  15. Oct-4 expression in pluripotent cells of the rhesus monkey.

    Science.gov (United States)

    Mitalipov, Shoukhrat M; Kuo, Hung-Chih; Hennebold, Jon D; Wolf, Don P

    2003-12-01

    The POU (Pit-Oct-Unc)-domain transcription factor, Oct-4, has become a useful marker of pluripotency in the mouse. It is found exclusively in mouse preimplantation-stage embryos after embryonic genome activation and is a characteristic of mouse embryonic stem (ES) cells, and its absence in knockout mice precludes inner cell mass (ICM) formation in blastocysts. Expression of Oct-4 has also been associated with pluripotency in primate cells. Here, we undertook a systematic study of Oct-4 expression in rhesus macaque preimplantation embryos produced by intracytoplasmic sperm injection and in ES cells before and after exposure to differentiating conditions in vitro. We also evaluated Oct-4 expression as a means of monitoring the extent of reprogramming following somatic cell nuclear transfer. Oct-4 was detected by reverse transcription-polymerase chain reaction and immunocytochemistry with a monoclonal antibody. Monkey pronuclear-stage zygotes and cleaving embryos up to the 8-cell stage showed no detectable Oct-4. Nuclear staining for Oct-4 first became obvious at the 16-cell stage, and a strong signal was observed in morula and compact morula stages. Both ICM and trophectodermal cell nuclei of monkey early blastocysts were positive for Oct-4. However, the signal was diminished in trophectodermal cells of expanded blastocysts, whereas expression remained high in ICM nuclei. Similar to the mouse, hatched monkey blastocysts showed strong Oct-4 expression in the ICM, with no detectable signal in the trophectoderm. Undifferentiated monkey ES cells derived from the ICM of in vitro-produced blastocysts expressed Oct-4, consistent with their pluripotent nature, whereas ES cell differentiation was associated with signal loss. Therefore, Oct-4 expression in the monkey, as in the mouse, provides a useful marker for pluripotency after activation of the embryonic genome. Finally, the observed lack or abnormal expression of Oct-4 in monkey nuclear transfer embryos suggests

  16. Developmental competence of oocytes after ICSI in the rhesus monkey.

    Science.gov (United States)

    Nusser, K D; Mitalipov, S; Widmann, A; Gerami-Naini, B; Yeoman, R R; Wolf, D P

    2001-01-01

    Oocyte quantity and quality are critical to assisted reproductive technology (ART), yet few assessments beyond counting metaphase II (MII) oocytes exist. In this study, 30 +/- 2 oocytes per cycle were recovered from rhesus monkeys subjected to follicular stimulation with human gonadotrophins, of which 15 +/- 1 were MII. Oocyte quality was investigated by monitoring the developmental potential of oocytes subjected to intracytoplasmic sperm injection (ICSI). Despite uniform fertilization rates (71 +/- 4%), progression of embryos to blastocysts varied when expressed as a monthly average, from 20 to 85%, with lows from February to April and again in October, which could be attributed to developmental failure of a significant number of oocyte cohorts (14 of 55). Blastocyst rates, after elimination of failed cohorts, were uniform over time (59 +/- 4%). Neither culture conditions, the number of follicular stimulations, nor the individual sperm or oocyte donor were associated specifically with developmental failure, suggesting that intrinsic differences between stimulation cycles account for the observed variation in developmental potential. The in-vivo developmental competence of ICSI-produced embryos grown to blastocysts in vitro was also assessed. Two ongoing pregnancies and the birth of a normal female, 'Blastulina', represent landmarks in efforts to expand the use of ART in the rhesus monkey.

  17. A MEG investigation of somatosensory processing in the rhesus monkey.

    Science.gov (United States)

    Wilson, Tony W; Godwin, Dwayne W; Czoty, Paul W; Nader, Michael A; Kraft, Robert A; Buchheimer, Nancy C; Daunais, James B

    2009-07-15

    The use of minimally and non-invasive neuroimaging methods in animal models has sharply increased over the past decade. Such studies have enhanced understanding of the neural basis of the physical signals quantified by these tools, and have addressed an assortment of fundamental and otherwise intractable questions in neurobiology. To date, these studies have almost exclusively utilized positron-emission tomography or variants of magnetic resonance based imaging. These methods provide largely indirect measures of brain activity and are strongly reliant on intact vasculature and normal blood-flow, which is known to be compromised in many clinical conditions. The current study provides the first demonstration of whole-head magnetoencephalography (MEG), a non-invasive and direct measure of neuronal activity, in a rhesus monkey, and in the process supplies the initial data on systems-level dynamics in somatosensory cortices. An adult rhesus monkey underwent three separate studies of tactile stimulation on the pad of the right second or fifth digit as whole-head MEG data were acquired. The neural generators of the primary neuromagnetic components were localized using an equivalent-current-dipole model. Second digit stimulation produced an initial cortical response peaking approximately 16 ms after stimulus onset in the contralateral somatosensory cortices, with a later response at approximately 96 ms in an overlapping or nearby neural area with a roughly orthogonal orientation. Stimulation of the fifth digit produced similar results, the main exception being a substantially weaker later response. We believe the 16 ms response is likely the monkey homologue of the human M50 response, as both are the earliest cortical response and localize to the contralateral primary somatosensory area. Thus, these data suggest that mechanoreception in nonhuman primates operates substantially faster than that in adult humans. More broadly, these results demonstrate that it is feasible to

  18. 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.

  19. 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.

  20. The rhesus monkey as a model for testing the immunological effects of space flight

    Science.gov (United States)

    Sonnenfeld, G.; Schaffar, L.; Schmitt, D. A.; Peres, C.; Miller, E. S.

    1994-08-01

    The Rhesus monkey has been proposed as a model for the effects of space flight on immunity. In order to determine the feasibility of the use of the Rhesus monkey as a model, we studied the use of Rhesus monkey cells for immunological procedures that have been shown to be affected by space flight in both rodents and humans. We have shown that both lymph node cells and peripheral blood leukocytes can be stained with monoclonal antibodies to detect the following surface markers: CD4, CD-8, Ia and surface immunoglobulin. Also, the level of Ia antigen expression was increased by treatment of the cells with human interferon-gamma. In addition, cells were induced to produce interferons and interleukins. Isolated neutrophils also demonstrated increased oxidative burst. These data indicate that the Rhesus monkey will be a useful model for space flight studies of immunity.

  1. Prenatal stress diminishes the cytokine response of leukocytes to endotoxin stimulation in juvenile rhesus monkeys.

    Science.gov (United States)

    Coe, Christopher L; Kramer, Marian; Kirschbaum, Clemens; Netter, Petra; Fuchs, Eberhard

    2002-02-01

    This study investigated whether exposing the fetal primate to repeated episodes of maternal stress would have long-lasting effects on the endotoxin-induced cytokine response and corticosteroid sensitivity of peripheral blood cells in juvenile animals. Pregnant rhesus monkeys were acutely aroused on a daily basis for 6 wk using an acoustical startle protocol, either early or late in the 24-wk pregnancy. To quantify cytokine responses and corticosteroid sensitivity in their offspring at 2 yr of age, whole blood cultures were stimulated with lipopolysaccharide and incubated with dexamethasone (DEX). TNFalpha and IL-6 levels were determined in the culture supernatants. The blood samples were collected from undisturbed monkeys under baseline conditions, as well as in an aroused state induced by a 2 h social separation. Juvenile monkeys from stressed pregnancies had significantly lower cellular cytokine responses compared with the undisturbed controls. When DEX was added to the cell cultures, it systematically inhibited TNFalpha and IL-6 production, bringing the values for control animals down into the range of the prenatally stressed animals. Lipopolysaccharide-induced cytokine production was also markedly suppressed by the experience of acute stress, reducing cytokine responses of controls to the levels found for prenatally disturbed monkeys under baseline conditions. Therefore, this study has demonstrated that prenatal disturbance can induce a lasting change in cytokine biology, which persists well beyond the fetal and infant stage. Further, these effects may be due to elevated hypothalamic-pituitary-adrenal activity in the prenatally stressed animals, because both DEX and acute arousal made the cells from control monkeys appear more similar to those from disturbed pregnancies.

  2. Prevalence of rhesus negativity among pregnant women

    Directory of Open Access Journals (Sweden)

    Ezhil Arasi Nagamuthu

    2016-08-01

    Conclusions: The prevalence of Rh D negative women is low when compared to Rh D positive women.There is a need for adequate counselling of pregnant women on the importance of Rh D negative factor during the antenatal period in order to prevent hemolytic disease of the newborn. [Int J Res Med Sci 2016; 4(8.000: 3305-3309

  3. Tonal frequency affects amplitude but not topography of rhesus monkey cranial EEG components.

    Science.gov (United States)

    Teichert, Tobias

    2016-06-01

    The rhesus monkey is an important model of human auditory function in general and auditory deficits in neuro-psychiatric diseases such as schizophrenia in particular. Several rhesus monkey studies have described homologs of clinically relevant auditory evoked potentials such as pitch-based mismatch negativity, a fronto-central negativity that can be observed when a series of regularly repeating sounds is disrupted by a sound of different tonal frequency. As a result it is well known how differences of tonal frequency are represented in rhesus monkey EEG. However, to date there is no study that systematically quantified how absolute tonal frequency itself is represented. In particular, it is not known if frequency affects rhesus monkey EEG component amplitude and topography in the same way as previously shown for humans. A better understanding of the effect of frequency may strengthen inter-species homology and will provide a more solid foundation on which to build the interpretation of frequency MMN in the rhesus monkey. Using arrays of up to 32 cranial EEG electrodes in 4 rhesus macaques we identified 8 distinct auditory evoked components including the N85, a fronto-central negativity that is the presumed homolog of the human N1. In line with human data, the amplitudes of most components including the N85 peaked around 1000 Hz and were strongly attenuated above ∼1750 Hz. Component topography, however, remained largely unaffected by frequency. This latter finding may be consistent with the known absence of certain anatomical structures in the rhesus monkey that are believed to cause the changes in topography in the human by inducing a rotation of generator orientation as a function of tonal frequency. Overall, the findings are consistent with the assumption of a homolog representation of tonal frequency in human and rhesus monkey EEG.

  4. 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.

  5. Cardiac arrhythmias induced by chloral hydrate in rhesus monkeys.

    Science.gov (United States)

    Han, Pengfei; Song, Haibo; Yang, Pingliang; Xie, Huiqi; Kang, Y James

    2011-06-01

    Chloral hydrate has been long used as a safe sedative and hypnotic drug in humans. However, reports on its cardiovascular adverse effects have been published from time to time. The present study was undertaken to use Rhesus monkeys as a model to define the dose regiment of chloral hydrate at which cardiac arrhythmias can be induced and the consequences of the cardiac events. Male Rhesus monkeys of 2-3 years old were intravenously infused with chloral hydrate starting at 50 mg/kg with an increasing increment of 25 mg/kg until the occurrence of cardiac arrhythmias. In addition, a traditional up-and-down dosing procedure was applied to define a single dose level at which cardiac arrhythmias can be induced. The data obtained showed that when the sequentially escaladed dose reached 125 mg/kg, cardiac arrhythmias occurred in all monkeys tested. The single effective dose to cause cardiac arrhythmias calculated from the crossover analysis was 143 ± 4 mg/kg. This value would be equivalent to 68.6 ± 1.9 mg/kg for children and 46.4 ± 1.3 mg/kg for adults in humans. Under either multiple or single dose condition, cardiac arrhythmias did not occur before 40 min after the onset of anesthesia induced by chloral hydrate. Cardiac arrhythmias were recovered without help at the end of the anesthesia in most cases, but also continued after the regain of consciousness in some cases. The cardiac arrhythmias were accompanied with compromised cardiac function including suppressed fractional shortening and ejection fraction. This study thus suggests that cautions need to be taken when chloral hydrate is used above certain levels and beyond a certain period of anesthesia, and cardiac arrhythmias induced by chloral hydrate need to be closely monitored because compromised cardiac function may occur simultaneously. In addition, patients with cardiac arrhythmias induced by chloral hydrate should be monitored even after they are recovered from the anesthesia.

  6. Collagen-induced arthritis in rhesus monkeys: Evaluation of markers for inflammation and joint degradation

    NARCIS (Netherlands)

    Hart, B.A. 't; Bank, R.A.; Roos, J.A.D.M. de; Brok, H.; Jonker, M.; Theuns, H.M.; Hakimi, J.; Koppele, J.M.Te.

    1998-01-01

    The objective of this study was to analyse parameters in rhesus monkey collagen-induced arthritis (CIA) with which the inflammation and destruction of the joints can be described in quantitative terms. CIA was induced in genetically susceptible and resistant monkeys, which can be distinguished on th

  7. Essentialism in the Absence of Language? Evidence from Rhesus Monkeys ("Macaca mulatta")

    Science.gov (United States)

    Phillips, Webb; Shankar, Maya; Santos, Laurie R.

    2010-01-01

    We explored whether rhesus monkeys (Macaca mulatta) share one important feature of human essentialist reasoning: the capacity to track category membership across radical featural transformations. Specifically, we examined whether monkeys--like children (Keil, 1989)--expect a transformed object to have the internal properties of its original…

  8. Hemopoietic stem cells in rhesus monkeys : surface antigens, radiosensitivity, and responses to GM-CSF

    NARCIS (Netherlands)

    J.J. Wielenga (Jenne)

    1990-01-01

    textabstractRhesus monkeys (Macaca mulatta) were bred at the Primate Center TNO, Rijswijk, The Netherlands!. Both male and female animals were used for the experiments. The monkeys weighed 2.5-4 kg and were 2-4 years old at the time of the experiment. They were all typed for RhLA-A, -B and -DR antig

  9. Parthenogenetic activation of rhesus monkey oocytes and reconstructed embryos.

    Science.gov (United States)

    Mitalipov, S M; Nusser, K D; Wolf, D P

    2001-07-01

    This study determines the efficiency of sequential calcium treatments (electroporation or ionomycin) combined with protein synthesis (cycloheximide) or phosphorylation inhibitors (6-dimethylaminopurine) or the specific maturation promoting factor (MPF) inhibitor, roscovitine, in inducing artificial activation and development of rhesus macaque parthenotes or nuclear transfer embryos. Exposure of oocytes arrested at metaphase II (MII) to ionomycin followed by 6-dimethylaminopurine or to electroporation followed by cycloheximide and cytochalasin B induced pronuclear formation and development to the blastocyst stage at a rate similar to control embryos produced by intracytoplasmic sperm injection. Parthenotes did not complete meiosis or extrude a second polar body, consistent with their presumed diploid status. In contrast, oocytes treated sequentially with ionomycin and roscovitine extruded the second polar body and formed a pronucleus at a rate higher than that observed in controls. Following reconstruction by nuclear transfer, activation with ionomycin/6-dimethylaminopurine resulted in embryos that contained a single pronucleus and no polar bodies. All nuclear transfer embryos activated with ionomycin/roscovitine contained one large pronucleus. However, a third of these embryos emitted one or two polar bodies, clearly containing chromatin material. In summary, we have identified simple yet effective methods of oocyte or cytoplast activation in the monkey, ionomycin/6-dimethylaminopurine, electroporation/cycloheximide/cytochalasin B, and ionomycin/roscovitine, which are applicable to parthenote or nuclear transfer embryo production.

  10. Psychobiology of early social attachment in rhesus monkeys. Clinical implications.

    Science.gov (United States)

    Kraemer, G W

    1997-01-15

    "Attachment" has been viewed as the process by which the infant bonds to a caregiver and develops and maintains affiliative social relationships. Whereas past theories suggested that the neurobiological mechanisms that enable the infant to engage in regulated social interactions develop autonomously, the more current view is that the organization of cognitive and emotional systems that regulate social behavior depends on early caregiver-infant attachment. It is well known that disruption of caregiver-infant attachment produces abnormal behavior and increases or decreases the activity of different brain neurochemical systems in rhesus monkeys. Furthermore, it has been suggested that these effects might serve as a model for the etiology of some forms of human psychopathology. Current research indicates that caregiver privation alters the development of usual interrelationships among the activity of several neurochemical and neuroendocrine systems and alters basic cognitive processes. In line with the idea that the caregiver usually exerts a potent organizing effect on the infant's psychobiology, the long-standing effects of caregiver privation on behavior and emotionality are probably attributable to changes in multiple regulatory systems and cognitive-emotional integration rather than restricted effects on the activity of any specific set of neurochemical systems.

  11. Rhesus monkeys see who they hear: spontaneous cross-modal memory for familiar conspecifics.

    Directory of Open Access Journals (Sweden)

    Ikuma Adachi

    Full Text Available Rhesus monkeys gather much of their knowledge of the social world through visual input and may preferentially represent this knowledge in the visual modality. Recognition of familiar faces is clearly advantageous, and the flexibility and utility of primate social memory would be greatly enhanced if visual memories could be accessed cross-modally either by visual or auditory stimulation. Such cross-modal access to visual memory would facilitate flexible retrieval of the knowledge necessary for adaptive social behavior. We tested whether rhesus monkeys have cross-modal access to visual memory for familiar conspecifics using a delayed matching-to-sample procedure. Monkeys learned visual matching of video clips of familiar individuals to photographs of those individuals, and generalized performance to novel videos. In crossmodal probe trials, coo-calls were played during the memory interval. The calls were either from the monkey just seen in the sample video clip or from a different familiar monkey. Even though the monkeys were trained exclusively in visual matching, the calls influenced choice by causing an increase in the proportion of errors to the picture of the monkey whose voice was heard on incongruent trials. This result demonstrates spontaneous cross-modal recognition. It also shows that viewing videos of familiar monkeys activates naturally formed memories of real monkeys, validating the use of video stimuli in studies of social cognition in monkeys.

  12. 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).

  13. Rhesus monkey neural stem cell transplantation promotes neural regeneration in rats with hippocampal lesions.

    Science.gov (United States)

    Ye, Li-Juan; Bian, Hui; Fan, Yao-Dong; Wang, Zheng-Bo; Yu, Hua-Lin; Ma, Yuan-Ye; Chen, Feng

    2016-09-01

    Rhesus monkey neural stem cells are capable of differentiating into neurons and glial cells. Therefore, neural stem cell transplantation can be used to promote functional recovery of the nervous system. Rhesus monkey neural stem cells (1 × 10(5) cells/μL) were injected into bilateral hippocampi of rats with hippocampal lesions. Confocal laser scanning microscopy demonstrated that green fluorescent protein-labeled transplanted cells survived and grew well. Transplanted cells were detected at the lesion site, but also in the nerve fiber-rich region of the cerebral cortex and corpus callosum. Some transplanted cells differentiated into neurons and glial cells clustering along the ventricular wall, and integrated into the recipient brain. Behavioral tests revealed that spatial learning and memory ability improved, indicating that rhesus monkey neural stem cells noticeably improve spatial learning and memory abilities in rats with hippocampal lesions.

  14. [A technique of rhesus monkey neural progenitor cells intravitreal transplant to rats].

    Science.gov (United States)

    Bian, Hui; Fan, Yao-Dong; Guo, Li-Yun; Yu, Hua-Lin

    2012-02-01

    To investigate a simple and effective intraocular xenotransplant technique of rhesus monkey neural progenitor cells to rats, mechanical injury was induced in the rat's right retina. And the GFP-labeled rhesus monkey neural progenitor cells suspension was slowly injected into the vitreous space of the right injured and left control eye. Confocal image suggested that the xenografted cells survived in both the injured and control eye, meanwhile the cells integrated in the injured right retina. The results demonstrated that intravitreal xenotransplant could be adopted as a simple and reliable method.

  15. 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

    2016-09-09

    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.

  16. Vestibular functions and sleep in space experiments. [using rhesus and owl monkeys

    Science.gov (United States)

    Perachio, A. A.

    1977-01-01

    Physical indices of sleep were continuously monitored in an owl monkey living in a chamber continuously rotating at a constant angular velocity. The electrophysiological data obtained from chronically implanted electrodes was analyzed to determine the chronic effects of vestibular stimulation on sleep and wakefulness cycles. The interaction of linear and angular acceleration on the vestibulo-ocular reflex was investigated in three rhesus monkeys at various angular accelerations.

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

    Science.gov (United States)

    Lee, Jin-Gyun; McKinney, Kimberly Q; Lee, Yong-Yook; Chung, Hae-Na; Pavlopoulos, Antonis J; Jung, Kook Y; Kim, Woong-Ki; Kuroda, Marcelo J; Han, David K; Hwang, Sunil

    2015-01-01

    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.

  18. 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.

  19. 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.

  20. Effect of radiation and age on immunoglobulin levels in rhesus monkeys (Macaca mulatta)

    Science.gov (United States)

    Stone, W. H.; Saphire, D. G.; Hackleman, S. M.; Braun, A. M.; Pennington, P.; Scheffler, J.; Wigle, J. C.; Cox, A. B.

    1994-01-01

    We report the results of a study on the immunoglobulin levels of rhesus monkeys (Macaca mulatta) in a colony consisting of the survivors of monkeys that received a single whole-body exposure to protons, electrons or X rays between 1964 and 1969. This colony has been maintained to assess the long-term effects of ionizing radiation on astronauts and high-flying pilots. Of the original 358 monkeys that were retained for lifetime studies, 129 (97 irradiated and 32 controls) were available for our study. We found no significant difference between the irradiated and control monkeys in mean levels of IgA, IgG and IgM, irrespective of the radiation treatment. The availability of these aged monkeys provided a unique opportunity to compare their immunoglobulin levels to those of other monkeys of various ages, and thus assess the effect of age on immunoglobulin levels. We found that only the IgA levels increase with age.

  1. Reproducibility of Perfusion Parameters of Optic Disc and Macula in Rhesus Monkeys by Optical Coherence Tomography Angiography

    Directory of Open Access Journals (Sweden)

    Jing Li

    2016-01-01

    Conclusions: The study is about the reproducibility of optic disc and macular perfusion parameters as measured by OCT angiography in healthy rhesus monkeys. Flow index measurement reproducibility is high for both the optic disc and macula of normal monkey eyes. OCT angiography might be a useful technique to assess changes when examining monkeys with experimental ocular diseases.

  2. Nuclear-mitochondrial incompatibility in interorder rhesus monkey-cow embryos derived from somatic cell nuclear transfer.

    Science.gov (United States)

    Kwon, Daekee; Koo, Ok-Jae; Kim, Min-Jung; Jang, Goo; Lee, Byeong Chun

    2016-10-01

    Monkey interorder somatic cell nuclear transfer (iSCNT) using enucleated cow oocytes yielded poor blastocysts development and contradictory results among research groups. Determining the reason for this low blastocyst development is a prerequisite for optimizing iSCNT in rhesus monkeys. The aim of this study was to elucidate nuclear-mitochondrial incompatibility of rhesus monkey-cow iSCNT embryos and its relationship to low blastocyst development. Cytochrome b is a protein of complex III of the electron transport chain (ETC). According to meta-analysis of amino acid sequences, the homology of cytochrome b is 75 % between rhesus monkeys and cattle. To maintain the function of ETC after iSCNT, 4n iSCNT embryos were produced by fusion of non-enucleated cow oocytes and rhesus monkey somatic cells. The blastocyst development rate of 4n iSCNT embryos was higher than that of 2n embryos (P monkey iSCNT embryos reconstructed with cow oocytes have nuclear-mitochondrial incompatibility due to fundamental species differences between rhesus monkeys and cattle. Nuclear-mitochondrial incompatibility seems to correlate with low ETC activity and extremely low blastocyst development of rhesus monkey-cow iSCNT embryos.

  3. The effect of chronic cocaine exposure throughout pregnancy on maternal and infant outcomes in the rhesus monkey.

    Science.gov (United States)

    Morris, P; Binienda, Z; Gillam, M P; Klein, J; McMartin, K; Koren, G; Duhart, H M; Slikker, W; Paule, M G

    1997-01-01

    To explore the effects of gestational cocaine exposure in a nonhuman primate model, pregnant rhesus monkeys were either treated (N = 10) with escalating doses of cocaine up to 7.5 mg/kg (IM), three times per day, 5 consecutive days per week, prior to conception and throughout gestation, or were not treated (N = 10) with cocaine at all. Substantial levels of both cocaine and its major metabolite, benzoylecgonine, were observed in samples of hair taken at birth from mothers and infants of the cocaine-treated group. Despite these differences in cocaine exposure, the experimental groups did not differ significantly with respect to maternal outcome, as measured by body weight again during pregnancy and length of pregnancy. On the other hand, the experimental groups did differ significantly with respect to infant outcome, as measured at birth by body weight, overall length, and crown circumference, all of which were decreased in the cocaine-treated group. A variety of reflexes tested at birth were normal in the cocaine-treated group. It was concluded that, in a rhesus monkey model, chronic cocaine exposure throughout pregnancy had no significant effect on maternal outcome, but did significantly affect infant outcome as assessed in this investigation.

  4. Structural differences among serum IgA proteins of chimpanzee, rhesus monkey and rat origin

    NARCIS (Netherlands)

    Endo, T.; Radl, J.; Mestecky, J.

    1997-01-01

    Asparagine-linked sugar chains were quantitatively released from chimpanzee, Rhesus monkey and rat IgA proteins as oligosaccharides by hydrazinolysis, converted to radioactive oligosaccharides by reduction with NaB3H4, and separated into neutral and two acidic fractions by paper electrophoresis. The

  5. 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

  6. The Neural Basis of Smooth Pursuit Eye Movements in the Rhesus Monkey Brain

    Science.gov (United States)

    Ilg, Uwe J.; Thier, Peter

    2008-01-01

    Smooth pursuit eye movements are performed in order to prevent retinal image blur of a moving object. Rhesus monkeys are able to perform smooth pursuit eye movements quite similar as humans, even if the pursuit target does not consist in a simple moving dot. Therefore, the study of the neuronal responses as well as the consequences of…

  7. Evidence for Motor Planning in Monkeys: Rhesus Macaques Select Efficient Grips when Transporting Spoons

    Science.gov (United States)

    Nelson, Eliza L.; Berthier, Neil E.; Metevier, Christina M.; Novak, Melinda A.

    2011-01-01

    McCarty and colleagues (1999) developed the elevated spoon task to measure motor planning in human infants. In this task, a spoon containing food was placed on an elevated apparatus that supported both ends of the spoon. The handle was oriented to the left or right on different trials. We presented naive adult rhesus monkeys (Macaca mulatta) with…

  8. Quantity Representation in Children and Rhesus Monkeys: Linear Versus Logarithmic Scales

    Science.gov (United States)

    Beran, Michael J.; Johnson-Pynn, Julie S.; Ready, Christopher

    2008-01-01

    The performances of 4- and 5-year-olds and rhesus monkeys were compared using a computerized task for quantity assessment. Participants first learned two quantity anchor values and then responded to intermediate values by classifying them as similar to either the large anchor or the small anchor. Of primary interest was an assessment of where the…

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

    NARCIS (Netherlands)

    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 change

  10. Comparison of anticonvulsant effects of clorazepate dipotassium and diazepam. Four week anticonvulsant study in Rhesus monkeys.

    Science.gov (United States)

    Plotnikoff, N P; O'Brien, G S

    1974-02-01

    Clorazepate dipotassium and diazepam were administered daily for the first 5 days of each week to Rhesus monkeys at equimolar doses and challanged once a week with a convulsant dose of pentylenetetrazol. Clorazepate exhibited sustained anticonvulsant activity throughout the second, third, and fourth weeks while diazepam was effective only during the second and third weeks.

  11. 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.

  12. Toxic shock due to Streptococcus pyogenes in a rhesus monkey (Macaca mulatta).

    Science.gov (United States)

    García, Anapatricia; Paul, Katherine; Beall, Bernard; McClure, Harold

    2006-09-01

    Recent years have seen a worldwide resurgence in serious infections caused by group A streptococci. This group includes Streptococcus pyogenes, one of the most common pathogens among children which causes diverse suppurative infections, such as pharyngitis, as well as nonsuppurative infections with sequelae, such as rheumatoid fever and rheumatic heart disease. S. pyogenes produces several superantigen-like erythrogenic toxins, which are believed to be associated with pyrogenicity, erythromatous skin reactions, and various immunologic and cytotoxic effects. These toxins also can cause myocardial necrosis. In addition, recently reported streptococcal infections in obstetric human patients appear to be clinically different from classic puerperal sepsis. Here, we report a case of spontaneous streptococcal infection in a pregnant female rhesus monkey (Macaca mulatta). In addition to lesions consistent with bacteremia and toxic shock, this animal had severe cardiac lesions resembling those described in humans with rheumatic heart disease. S. pyogenes was isolated from intracardiac blood, liver, placenta, and fetal tissues. This isolate also had a unique M protein gene.

  13. Rhesus monkeys (Macaca mulatta detect rhythmic groups in music, but not the beat.

    Directory of Open Access Journals (Sweden)

    Henkjan Honing

    Full Text Available It was recently shown that rhythmic entrainment, long considered a human-specific mechanism, can be demonstrated in a selected group of bird species, and, somewhat surprisingly, not in more closely related species such as nonhuman primates. This observation supports the vocal learning hypothesis that suggests rhythmic entrainment to be a by-product of the vocal learning mechanisms that are shared by several bird and mammal species, including humans, but that are only weakly developed, or missing entirely, in nonhuman primates. To test this hypothesis we measured auditory event-related potentials (ERPs in two rhesus monkeys (Macaca mulatta, probing a well-documented component in humans, the mismatch negativity (MMN to study rhythmic expectation. We demonstrate for the first time in rhesus monkeys that, in response to infrequent deviants in pitch that were presented in a continuous sound stream using an oddball paradigm, a comparable ERP component can be detected with negative deflections in early latencies (Experiment 1. Subsequently we tested whether rhesus monkeys can detect gaps (omissions at random positions in the sound stream; Experiment 2 and, using more complex stimuli, also the beat (omissions at the first position of a musical unit, i.e. the 'downbeat'; Experiment 3. In contrast to what has been shown in human adults and newborns (using identical stimuli and experimental paradigm, the results suggest that rhesus monkeys are not able to detect the beat in music. These findings are in support of the hypothesis that beat induction (the cognitive mechanism that supports the perception of a regular pulse from a varying rhythm is species-specific and absent in nonhuman primates. In addition, the findings support the auditory timing dissociation hypothesis, with rhesus monkeys being sensitive to rhythmic grouping (detecting the start of a rhythmic group, but not to the induced beat (detecting a regularity from a varying rhythm.

  14. Endocrine and pharmacological factors which influence the onset of labour in rhesus monkeys.

    Science.gov (United States)

    Novy, M J

    1977-01-01

    Indomethacin administration in late pregnancy prolonged gestation in caged rhesus monkeys and inhibited premature labour and postponed delivery in chronically catheterized monkey fetuses. Chronic indomethacin treatment was associated with a reduction in the urinary excretion of a prostaglandin metabolite, a potent inhibitory effect on myometrial cyclic AMP phosphodiesterase, and severe oligohydramnios in pre-term and post-term fetuses. Experimental anencephaly (functional hypophysectomy) of the rhesus fetus results in lowered concentrations of maternal oestradiol and loss of the precise control of gestational length, with 40% of fetuses delivering beyond term. Corticotropin (ACTH) infused into the fetus results in raised concentrations of fetal and maternal cortisol, progesterone and oestrogens. Progesterone concentrations in peripheral blood apparently have little bearing on uterine quiescence in the rhesus monkey, since the concentrations of progesterone in maternal and fetal blood vary directly with uterine activity. The results of chronic infusion of corticotropin in the fetal monkey support the theory that in the monkey parturition is mediated by increased oestrogen production by the fetoplacental unit and by a rise in the concentrations of oestrone and prostaglandin in the amniotic fluid.

  15. 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.

  16. 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

  17. Exploring a partially enclosed space by lead-exposed female rhesus monkeys.

    Science.gov (United States)

    Lasky, R E; Laughlin, N K

    2001-01-01

    Beginning on Day 8 postpartum, lead acetate was administered to female rhesus monkeys (n=48). Their blood lead levels rose to 35-40 microg/dl (the level maintained for the duration of the study period) by 12 weeks of age. Weekly, these lead-exposed monkeys and their controls (n=23) were placed in a partially enclosed space from the second postnatal week until they escaped three times or were 26 weeks old. The lead-exposed monkeys exhibited more fear, were more likely to be agitated, and climbed more frequently during the first testing session. In subsequent sessions, they more frequently explored the periphery of the test area than the controls. The lead-exposed monkeys also tended to escape sooner although that trend did not consistently reach the.05 level of significance. The increased activity and agitation of the lead-exposed monkeys is suggestive of deficits reported in human children with high blood lead levels.

  18. A pilot study on transient ischemic stroke induced with endothelin-1 in the rhesus monkeys

    Science.gov (United States)

    Dai, PeiMin; Huang, Hui; Zhang, Lin; He, Jing; Zhao, XuDong; Yang, FuHan; Zhao, Ning; Yang, JianZhen; Ge, LongJiao; Lin, Yu; Yu, HuaLin; Wang, JianHong

    2017-01-01

    Endothelin-1 (ET-1), a vasoconstrictor, has recently been used to induce focal ischemia in rodents and marmoset monkeys. The rhesus monkey, however, has numerous advantages to the rodent and marmoset that make it a superior and irreplaceable animal model for studying stroke in the brain. In the present study, after mapping the preferred hand representation in two healthy male monkeys with intracortical micro-stimulation, ET-1 was microinjected into the contralateral motor cortex (M1) to its preferred hand. The monkeys had been trained in three manual dexterity tasks before the microinjection and were tested for these tasks following the ET-1 injection. Brain Magnetic Resonance Imaging scans were performed 1, 7, 14 and 28 days post ischemia. It was found that ET-1 impaired the manual dexterity of the monkeys in the vertical slot and rotating Brinkman board tasks 3–8 days after the injection. Brain imaging found that severe edema was present 7 days after the focal ischemia. This data suggest that ET-1 can induce transient ischemic stroke in rhesus monkey and that ET-1 induced focal ischemia in non-human primates is a potential model to study the mechanism of stroke and brain repair after stroke. PMID:28358140

  19. Determination of the Infectious Dose of Helicobacter pylori during Primary and Secondary Infection in Rhesus Monkeys (Macaca mulatta)

    OpenAIRE

    Solnick, Jay V.; Hansen, Lori M.; Canfield, Don R.; Parsonnet, Julie

    2001-01-01

    We sought to determine the infectious dose of Helicobacter pylori during primary and secondary infection in the rhesus monkey and to determine whether preinoculation acid suppression is necessary to produce colonization. Mixed inoculation with three human-derived strains showed that H. pylori J166 is particularly adapted to colonization of rhesus monkeys, since it outcompeted two other strains. The minimum infectious dose of H. pylori J166 was 104 bacteria in specific-pathogen (H. pylori)-fre...

  20. Effect of substrates on the mechanical performance of rhesus monkey papillary muscle.

    Science.gov (United States)

    Snow, T R

    1980-04-15

    This study examines the effect of different substrates on mechanical performance of excised papillary muscles from rhesus monkeys which had been divided into a control group and an experimental group fed a high fat diet for 5 months prior to sacrifice. The results show that performance is affected by availabel substrate for both groups. The performance of the experimental group was depressed relative to control with the short chain fatty acid, butyrate (C4), producing a monotonically decreasing force-frequency response. Relative to the other mammals, isolated rhesus papillary muscles exhibited a protracted treppe which was sensitive to beta-adrenergic blockade with propranolol.

  1. 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.

  2. Piracetam-induced changes on the brainstem auditory response in anesthetized juvenile rhesus monkeys (Macaca mulatta). Report of two clinical cases.

    Science.gov (United States)

    Durand-Rivera, A; Gonzalez-Pina, R; Hernandez-Godinez, B; Ibanez-Contreras, A; Bueno-Nava, A; Alfaro-Rodriguez, A

    2012-10-01

    We describe two clinical cases and examine the effects of piracetam on the brainstem auditory response in infantile female rhesus monkeys (Macaca mulatta). We found that the interwave intervals show a greater reduction in a 3-year-old rhesus monkey compared to a 1-year-old rhesus monkey. In this report, we discuss the significance of these observations. © 2012 John Wiley & Sons A/S.

  3. An assessment of domain-general metacognitive responding in rhesus monkeys.

    Science.gov (United States)

    Brown, Emily Kathryn; Templer, Victoria L; Hampton, Robert R

    2017-02-01

    Metacognition is the ability to monitor and control one's cognition. Monitoring may involve either public cues or introspection of private cognitive states. We tested rhesus monkeys (Macaca mulatta) in a series of generalization tests to determine which type of cues control metacognition. In Experiment 1, monkeys learned a perceptual discrimination in which a "decline-test" response allowed them to avoid tests and receive a guaranteed small reward. Monkeys declined more difficult than easy tests. In Experiments 2-4, we evaluated whether monkeys generalized this metacognitive responding to new perceptual tests. Monkeys showed a trend toward generalization in Experiments 2 & 3, and reliable generalization in Experiment 4. In Experiments 5 & 6, we presented the decline-test response in a delayed matching-to-sample task. Memory tests differed from perceptual tests in that the appearance of the test display could not control metacognitive responding. In Experiment 6, monkeys made prospective metamemory judgments before seeing the tests. Generalization across perceptual tests with different visual properties and mixed generalization from perceptual to memory tests provide provisional evidence that domain-general, private cues controlled metacognition in some monkeys. We observed individual differences in generalization, suggesting that monkeys differ in use of public and private metacognitive cues.

  4. Predicting rhesus monkey eye movements during natural-image search.

    Science.gov (United States)

    Segraves, Mark A; Kuo, Emory; Caddigan, Sara; Berthiaume, Emily A; Kording, Konrad P

    2017-03-01

    There are three prominent factors that can predict human visual-search behavior in natural scenes: the distinctiveness of a location (salience), similarity to the target (relevance), and features of the environment that predict where the object might be (context). We do not currently know how well these factors are able to predict macaque visual search, which matters because it is arguably the most popular model for asking how the brain controls eye movements. Here we trained monkeys to perform the pedestrian search task previously used for human subjects. Salience, relevance, and context models were all predictive of monkey eye fixations and jointly about as precise as for humans. We attempted to disrupt the influence of scene context on search by testing the monkeys with an inverted set of the same images. Surprisingly, the monkeys were able to locate the pedestrian at a rate similar to that for upright images. The best predictions of monkey fixations in searching inverted images were obtained by rotating the results of the model predictions for the original image. The fact that the same models can predict human and monkey search behavior suggests that the monkey can be used as a good model for understanding how the human brain enables natural-scene search.

  5. Anti-implantation activity of luteal phase mifepristone administration is not mimicked by prostaglandin synthesis inhibitor or prostaglandin analogue in the rhesus monkey.

    Science.gov (United States)

    Nayak, N R; Ghosh, D; Lasley, B L; Sengupta, J

    1997-02-01

    The use of mifepristone as an anti-implantation agent in the primate has been explored in the rhesus monkey with two specific aims: (i) to determine the contraceptive efficacy of very low-dose mifepristone administered on mated cycle days 16, 17, and 18; and (ii) to test the hypothesis that alteration in endometrial prostaglandin milieu by using either prostaglandin analogue or prostaglandin synthesis inhibitor can intervene the antifertility effect induced by mifepristone. Thirty female monkeys were randomly assigned to one of the six treatment groups. Five monkeys in the control group (group 1) were subjected to mating during cycle days 8-22. Four out of five monkeys became pregnant in the first mated cycle (80%) with detection of serum mCG by 12.7 +/- 1.5 days after ovulation. In group 2, 12 mated cycles were studied in five monkeys, mifepristone [RU486, 2 mg/day/animal, s.c. in 1 ml vehicle (1:4, benzyl benzoate:olive oil, v/v)] was given on cycle days 16, 17, and 18. In this group, no pregnancy was observed, thus providing complete pregnancy protection. Though there was an apparent extension of treatment cycle lengths in five cases with no incidence of inter-menstrual bleeding or spotting, there were no significant changes in serum estradiol (E) and progesterone (P). In group 3, four monkeys received prostaglandin (PG) synthesis inhibitor, diclofenac sodium (D, 25 mg/day/animal, i.m.) on cycle days 16, 17, and 18 in seven ovulatory menstrual cycles. Four of these cycles (57%) resulted in normal pregnancies; however, mCG detection (16.8 +/- 1.2 days after ovulation) was significantly (p post-coital emergency contraception. However, the hypothesis that altered endometrial prostaglandin milieu may be responsible for mediating the anti-implantation effect of RU486 does not appear to be tenable based on our results in the rhesus monkey.

  6. Isolation and characterization of novel rhesus monkey embryonic stem cell lines.

    Science.gov (United States)

    Mitalipov, Shoukhrat; Kuo, Hung-Chih; Byrne, James; Clepper, Lisa; Meisner, Lorraine; Johnson, Julie; Zeier, Renee; Wolf, Don

    2006-10-01

    ESCs are important as research subjects since the mechanisms underlying cellular differentiation, expansion, and self-renewal can be studied along with differentiated tissue development and regeneration in vitro. Furthermore, human ESCs hold promise for cell and tissue replacement approaches to treating human diseases. The rhesus monkey is a clinically relevant primate model that will likely be required to bring these clinical applications to fruition. Monkey ESCs share a number of properties with human ESCs, and their derivation and use are not affected by bioethical concerns. Here, we summarize our experience in the establishment of 18 ESC lines from rhesus monkey preimplantation embryos generated by the application of the assisted reproductive technologies. The newly derived monkey ESC lines were maintained in vitro without losing their chromosomal integrity, and they expressed markers previously reported present in human and monkey ESCs. We also describe initial efforts to compare the pluripotency of ESC lines by expression profiling, chimeric embryo formation, and in vitro-directed differentiation into endodermal, mesodermal, and ectodermal lineages.

  7. Effect of rotopositioning on the growth and maturation of mandibular bone in immobilized Rhesus monkeys

    Science.gov (United States)

    Simmons, D. J.; Parvin, C.; Smith, K. C.; France, P.; Kazarian, L.

    1986-01-01

    The rates of bone formation and mineralization in the mandibular cortex of juvenile Rhesus monkeys exposed to immobilization/rotopositioning are evaluated. The monkeys were restrained in a supine position and rotated 90 deg every 30 minutes through a full 360 deg for 14 days. The microscopic distribution of mineral densities in osteonal bone and the porosity of cortical bone are studied using microradiographs, and osteon closure rates are assessed using tetracycline labeling; normal distributions of osteons of different mineral density and cortical bone porosity values are observed. It is concluded that 14 days of immobilization/rotopositioning did not cause abnormal changes in osteon mineralization, cortical porosity, and osteon closure rates.

  8. Early experience affects the intergenerational transmission of infant abuse in rhesus monkeys.

    Science.gov (United States)

    Maestripieri, Dario

    2005-07-01

    Maternal abuse of offspring in macaque monkeys shares some similarities with child maltreatment in humans, including its transmission across generations. This study used a longitudinal design and a cross-fostering experiment to investigate whether abusive parenting in rhesus macaques is transmitted from mothers to daughters and whether transmission occurs through genetic or experiential factors. Nine of 16 females who were abused by their mothers in their first month of life, regardless of whether they were reared by their biological mothers or by foster mothers, exhibited abusive parenting with their firstborn offspring, whereas none of the females reared by nonabusive mothers did. These results suggest that the intergenerational transmission of infant abuse in rhesus monkeys is the result of early experience and not genetic inheritance. The extent to which the effects of early experience on the intergenerational transmission of abusive parenting are mediated by social learning or experience-induced physiological alterations remains to be established.

  9. Establishment of AIDS Animal Model with SIVmac239 Infected Chinese Rhesus Monkey

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In the present research, two Chinese rhesus monkeys were inoculated intravenously with 5000 TCID50 of SIVmac239. The changes in the numbers of CD4+T lymphocyte in peripheral blood,plasma viral loads, proviral DNA and humoral antibodies against virus were periodically monitored during 121 days. At the early stage of infection, proviral DNA had been detected in PBMCs, and infectious SIVmac239 virus had been isolated from PBMCs. At the same period, the numbers of CD4+T lymphocytes were significantly decreased, and maintained at low level during the 121-day period of infection. Plasma viral loads reached the peak at week 2 post-inoculation and kept at a steady state subsequently. Moreover, antibodies against viral proteins were detected from plasma. All the results showed that the two Chinese rhesus monkeys had been infected with SIVmac239 successfully. This animal model can be applied for further AIDS researches.

  10. Empty Sets as Part of the Numerical Continuum: Conceptual Precursors to the Zero Concept in Rhesus Monkeys

    Science.gov (United States)

    Merritt, Dustin J.; Rugani, Rosa; Brannon, Elizabeth M.

    2009-01-01

    The goal of the current research was to explore whether monkeys possess conceptual precursors necessary for understanding zero. We trained rhesus monkeys on a nonsymbolic numerical matching-to-sample task, and on a numerical ordering task. We then introduced nondifferentially reinforced trials that contained empty sets to determine whether monkeys…

  11. Heterologous Prime/Boost Immunization of Rhesus Monkeys by Using Diverse Poxvirus Vectors▿

    OpenAIRE

    Santra, Sampa; Sun, Yue; Parvani, Jenny G.; Philippon, Valerie; Wyand, Michael S.; Manson, Kelledy; Gomez-Yafal, Alicia; Mazzara, Gail; Panicali, Dennis; Markham, Phillip D.; David C Montefiori; Letvin, Norman L.

    2007-01-01

    As the diversity of potential immunogens increases within certain classes of vectors, the possibility has arisen of employing heterologous prime/boost immunizations using diverse members of the same family of vectors. The present study was initiated to explore the use of divergent pox vectors in a prime/boost regimen to elicit high-frequency cellular immune responses to human immunodeficiency virus type 1 envelope and simian immunodeficiency virus gag in rhesus monkeys. We demonstrated that m...

  12. A 75-year pictorial history of the Cayo Santiago rhesus monkey colony.

    Science.gov (United States)

    Kessler, Matthew J; Rawlins, Richard G

    2016-01-01

    This article presents a pictorial history of the free-ranging colony of rhesus monkeys (Macaca mulatta) on Cayo Santiago, Puerto Rico, in commemoration of the 75th anniversary of its establishment by Clarence R. Carpenter in December 1938. It is based on a presentation made by the authors at the symposium, Cayo Santiago: 75 Years of Leadership in Translational Research, held at the 36th Annual Meeting of the American Society of Primatologists in San Juan, Puerto Rico, on 20 June 2013.

  13. Renal Medullary Solute Depletion Resulting from Psychogenic Polydipsia in a Rhesus Monkey

    Science.gov (United States)

    1988-01-01

    O ADH would normally indicate nerphrovenic served to have poivdipsia and an unthnftv diabetes insipidus . however, oae would expect the appearance...at resulting in obesity. Four weeks before the onset of 1.000. On day 5. the specific gravity was 1.005. and polydipsia. the diet was restricted to 100...medullary solute depletion. One year after diagnosis tion for a rhesus monkey fed a commercial dry diet .’ and treatment, there was no evidence of

  14. Pharmacokinetics of His-tag recombinant human endostatin in Rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    Hai-feng SONG; Xiu-wen LIU; Hai-ning ZHANG; Bao-zhen ZHU; Shou-jun YUAN; Shang-yi LIU; Zhong-ming TANG

    2005-01-01

    Aim: To study the pharmacokinetics and accumulation of an Escherichia coliexpressed His-tag fused recombinant human endostatin (rh-endostatin) in Rhesus monkeys. Methods: Rh-endostatin was iv or sc injected in Rhesus monkeys, and the rh-endostatin concentration in serum samples was determined by an enzyme immunoassay (EIA) method. The serum drug concentration-time data were analyzed by compartmental analysis using the practical pharmacokinetic program 3p97.Results: Following iv administration at a dose rate of 1.5, 4.5, and 13.5 mg/kg in rhesus monkeys, the concentration-time curves of rh-endostatin were best fitted to a three-compartment open model. AUC(0-∞) linearly increased with dose, while Cls exhibited no significant difference among different dose groups. The terminal half-lives (λ3) were 8±8, 3.1±1.4, and 20±14 h, respectively. After sc administration at a dose rate of 1.5 mg/kg, the concentration-time curve was best fitted to a two-compartment open model, with a terminal half-life (T1/2β) of 8±3 h.Bioavailability following sc injection was approximately 70%±3%. After consecutive iv injection of rh-endostatin at a dose rate of 1.5 mg.kg-1.d-1 for 7 d, the AUC(0-24 h) substantially increased from 22± 13 mg.h.L-1 (d 1) to 50±29 mg.h.L-1 (d 7), with an accumulation factor of 2.3±0.6 (P<0.05). Conclusion: The pharmacokinetic behavior of rh-endostatin in Rhesus monkeys complies with linear kinetics within the examined dose range. It tends to be accumulated in bodies after repeated administration at a dose level of 1.5 mg.kg-1.d-1 for more than 7 consecutive days.

  15. Extensive Spinal Decussation and Bilateral Termination of Cervical Corticospinal Projections in Rhesus Monkeys

    OpenAIRE

    2009-01-01

    To examine neuroanatomical mechanisms underlying fine motor control of the primate hand, adult Rhesus monkeys underwent injections of biotinylated dextran amine (BDA) into the right motor cortex. Spinal axonal anatomy was examined using detailed serial-section reconstruction and modified stereological quantification. 87% of corticospinal tract (CST) axons decussated in the medullary pyramids and descended through the contralateral dorsolateral tract of the spinal cord. 11% of CST axons projec...

  16. An alternative method of chronic cerebrospinal fluid collection via the cisterna magna in conscious rhesus monkeys.

    Science.gov (United States)

    Gilberto, David B; Zeoli, Angela H; Szczerba, Peter J; Gehret, John R; Holahan, Marie A; Sitko, Gary R; Johnson, Colena A; Cook, Jacquelynn J; Motzel, Sherri L

    2003-07-01

    Models of chronic cerebrospinal fluid (CSF) collection previously have been established for nonhuman primates and canines; many of these methods implement stainless-steel cannulas into the lateral or 4th ventricles or catheters into the cerebral or spinal subarachnoid space. These models have proved successful and reliable but unfortunately require invasive techniques to pass through the skull or require a laminectomy to enter the spinal subarachnoid space, involve the use of expensive and highly specialized stereotaxic equipment for the precise placement of the implants, and may require exteriorized hardware which is cumbersome to maintain and unaesthetic. The model we developed for the rhesus monkey allows for direct access to CSF outflow from the cisterna magna by using a 3.5-French fenestrated silicone catheter which was placed 1.0 cm into the cisterna. The catheter was attached to a titanium port placed subcutaneously between the scapulae to permit easy access for sampling CSF in a conscious, chaired rhesus monkey. We currently have instrumented animals from which we have consistently collected CSF for over 18 months. This novel, economical, less-invasive method permits chronic, reliable collection of CSF in conscious rhesus monkeys and has the additional advantages that the model is easier to maintain and more aesthetic.

  17. 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.

  18. Sex differences in rhesus monkey toy preferences parallel those of children.

    Science.gov (United States)

    Hassett, Janice M; Siebert, Erin R; Wallen, Kim

    2008-08-01

    Sex differences in toy preferences in children are marked, with boys expressing stronger and more rigid toy preferences than girls, whose preferences are more flexible. Socialization processes, parents, or peers encouraging play with gender-specific toys are thought to be the primary force shaping sex differences in toy preference. A contrast in view is that toy preferences reflect biologically-determined preferences for specific activities facilitated by specific toys. Sex differences in juvenile activities, such as rough-and-tumble play, peer preferences, and infant interest, share similarities in humans and monkeys. Thus if activity preferences shape toy preferences, male and female monkeys may show toy preferences similar to those seen in boys and girls. We compared the interactions of 34 rhesus monkeys, living within a 135 monkey troop, with human wheeled toys and plush toys. Male monkeys, like boys, showed consistent and strong preferences for wheeled toys, while female monkeys, like girls, showed greater variability in preferences. Thus, the magnitude of preference for wheeled over plush toys differed significantly between males and females. The similarities to human findings demonstrate that such preferences can develop without explicit gendered socialization. We offer the hypothesis that toy preferences reflect hormonally influenced behavioral and cognitive biases which are sculpted by social processes into the sex differences seen in monkeys and humans.

  19. Selective hippocampal lesions yield nonspatial memory impairments in rhesus monkeys.

    Science.gov (United States)

    Doré, F Y; Thornton, J A; White, N M; Murray, E A

    1998-01-01

    Monkeys with removals of medial temporal lobe (MTL) structures are widely recognized as valid models of human global anterograde amnesia, a syndrome that arises consequent to damage to a finite set of brain structures situated in the medial temporal lobe and/or medial diencephalon. However, a comparison of memory deficits in human and nonhuman primates with MTL damage has presented a long-standing puzzle. Whereas amnesic patients are impaired in learning object discrimination problems, monkeys with MTL damage are typically not. One possible explanation for this difference is that object discrimination tasks for humans and monkeys differ in that the former but not the latter requires the use of contextual information. If this analysis is correct, monkeys with MTL damage might be disadvantaged in learning to discriminate similar objects presented in different contexts. To test this possibility, we evaluated the effects of excitotoxic lesions of one of the MTL structures, the hippocampus, on the rate of learning of discrimination problems embedded within unique contexts. Monkeys with hippocampal lesions were impaired relative to controls in learning object discrimination problems of this type. These findings strongly support the idea that the difference in the effect on object memory of MTL damage in human and nonhuman primates is due to a difference in the opportunity to employ contextual cues rather than to a difference in the organization of memory.

  20. Social facilitation of cognition in rhesus monkeys: audience vs. coaction

    Directory of Open Access Journals (Sweden)

    Amélie J. Reynaud

    2015-12-01

    Full Text Available Social psychology has long established that the mere presence of a conspecific, be it an active co-performer (coaction effect, or a passive spectator (audience effect changes behavior in humans. Yet, the process mediating this fundamental social influence has so far eluded us. Brain research and its nonhuman primate animal model, the rhesus macaque, could shed new light on this long debated issue. For this approach to be fruitful, however, we need to improve our patchy knowledge about social presence influence in rhesus macaques. Here, seven adults (two dyads and one triad performed a simple cognitive task consisting in touching images to obtain food treats, alone versus in presence of a co-performer or a spectator. As in humans, audience sufficed to enhance performance to the same magnitude as coaction. Effect sizes were however 4 times larger than those typically reported in humans in similar tasks. Both findings are an encouragement to pursue brain and behavior research in the rhesus macaque to help solve the riddle of social facilitation mechanisms.

  1. Social Facilitation of Cognition in Rhesus Monkeys: Audience Vs. Coaction.

    Science.gov (United States)

    Reynaud, Amélie J; Guedj, Carole; Hadj-Bouziane, Fadila; Meunier, Martine; Monfardini, Elisabetta

    2015-01-01

    Social psychology has long established that the mere presence of a conspecific, be it an active co-performer (coaction effect), or a passive spectator (audience effect) changes behavior in humans. Yet, the process mediating this fundamental social influence has so far eluded us. Brain research and its nonhuman primate animal model, the rhesus macaque, could shed new light on this long debated issue. For this approach to be fruitful, however, we need to improve our patchy knowledge about social presence influence in rhesus macaques. Here, seven adults (two dyads and one triad) performed a simple cognitive task consisting in touching images to obtain food treats, alone vs. in presence of a co-performer or a spectator. As in humans, audience sufficed to enhance performance to the same magnitude as coaction. Effect sizes were however four times larger than those typically reported in humans in similar tasks. Both findings are an encouragement to pursue brain and behavior research in the rhesus macaque to help solve the riddle of social facilitation mechanisms.

  2. Roll tilt psychophysics in rhesus monkeys during vestibular and visual stimulation.

    Science.gov (United States)

    Lewis, Richard F; Haburcakova, Csilla; Merfeld, Daniel M

    2008-07-01

    How does the brain calculate the spatial orientation of the head relative to gravity? Psychophysical measurements are critical to investigate this question, but such measurements have been limited to humans. In non-human primates, behavioral measures have focused on vestibular-mediated eye movements, which do not reflect percepts of head orientation. We have therefore developed a method to measure tilt perception in monkeys, derived from the subjective visual vertical (SVV) task. Two rhesus monkeys were trained to align a light bar parallel to gravity and performed this task during roll tilts, centrifugation, and roll optokinetic stimulation. The monkeys accurately aligned the light bar with gravity during static roll tilts but also demonstrated small orientation-dependent misperceptions of the tilt angle analogous to those measured in humans. When the gravito-inertial force (GIF) rotated dynamically in the roll plane, SVV responses remained closely aligned with the GIF during roll tilt of the head (coplanar canal rotational cues present), lagged slightly behind the GIF during variable-radius centrifugation (no canal cues present), and shifted gradually during fixed-radius centrifugation (orthogonal yaw canal cues present). SVV responses also deviated away from the earth-vertical during roll optokinetic stimulation. These results demonstrate that rotational cues derived from the semicircular canals and visual system have prominent effects on psychophysical measurements of roll tilt in rhesus monkeys and therefore suggest that a central synthesis of graviceptive and rotational cues contributes to percepts of head orientation relative to gravity in non-human primates.

  3. Morphological changes of an inflammatory myopathy in rhesus monkeys with simian acquired immunodeficiency syndrome.

    Science.gov (United States)

    Dalakas, M C; Gravell, M; London, W T; Cunningham, G; Sever, J L

    1987-09-01

    Eleven of 25 rhesus monkeys which died of simian acquired immunodeficiency syndrome (SAIDS) caused by infection with a type D retrovirus related to Mason-Pfizer monkey virus showed evidence of muscle weakness and atrophy and had elevated levels of muscle enzymes. Biopsies of affected muscle studied with enzyme histochemistry showed the characteristic features of polymyositis. Inflammatory cells consisting of lymphocytes, macrophages, and large vacuolated bizarre-shaped cells of undetermined type were surrounding or invading muscle fibers and were present in the perivascular spaces and endomysia septa. Within the perivascular infiltrates, lymphocytes were abundant but very few macrophages were present. Other myopathic features including profound proliferation of fibrous tissue, necrosis, and phagocytosis of muscle fibers were noted to a variable degree. The retrovirus was isolated from affected muscles. The clinical and historical features of polymyositis in rhesus monkeys with SAIDS are very similar to those of human polymyositis. The polymyositis in SAIDS induced by a type D retrovirus related to Mason-Pfizer monkey virus is an excellent primate model to study the mechanism and morphological changes of viral-induced muscle damage.

  4. 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.

  5. 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.

  6. 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.

  7. Differential expression of anti-glycan antibodies in schistosome-infected humans, rhesus monkeys and mice

    Science.gov (United States)

    Luyai, Anthony E; Heimburg-Molinaro, Jamie; Prasanphanich, Nina Salinger; Mickum, Megan L; Lasanajak, Yi; Song, Xuezheng; Nyame, A Kwame; Wilkins, Patricia; Rivera-Marrero, Carlos A; Smith, David F; Van Die, Irma; Secor, W Evan; Cummings, Richard D

    2014-01-01

    Schistosomiasis is a debilitating parasitic disease of humans, endemic in tropical areas, for which no vaccine is available. Evidence points to glycan antigens as being important in immune responses to infection. Here we describe our studies on the comparative humoral immune responses to defined schistosome-type glycan epitopes in Schistosoma mansoni-infected humans, rhesus monkeys and mice. Rhesus anti-glycan responses over the course of infection were screened on a defined glycan microarray comprising semi-synthetic glycopeptides terminating with schistosome-associated or control mammalian-type glycan epitopes, as well as a defined glycan microarray of mammalian-type glycans representing over 400 glycan structures. Infected rhesus monkeys generated a high immunoglobulin G (IgG) antibody response to the core xylose/core α3 fucose epitope of N-glycans, which peaked at 8–11 weeks post infection, coinciding with maximal ability to kill schistosomula in vitro. By contrast, infected humans generated low antibody levels to this epitope. At 18 months following praziquantel therapy to eliminate the parasite, antibody levels were negligible. Mice chronically infected with S. mansoni generated high levels of anti-fucosylated LacdiNAc (GalNAcβ1, 4(Fucα1, 3)GlcNAc) IgM antibodies, but lacked a robust response to the core xylose/core α3 fucose N-glycan antigens compared with other species studied, and their sera demonstrated an intermediate level of schistosomula killing in vitro. These differential responses to parasite glycan antigens may be related to the ability of rhesus monkeys to self-cure in contrast to the chronic infection seen in humans and mice. Our results validate defined glycan microarrays as a useful technology to evaluate diagnostic and vaccine antigens for schistosomiasis and perhaps other infections. PMID:24727442

  8. Rhesus monkeys (Macaca mulatta) discriminate between knowing and not knowing and collect information as needed before acting.

    Science.gov (United States)

    Hampton, Robert R; Zivin, Aaron; Murray, Elisabeth A

    2004-10-01

    Humans use memory awareness to determine whether relevant knowledge is available before acting, as when we determine whether we know a phone number before dialing. Such metacognition, or thinking about thinking, can improve selection of appropriate behavior. We investigated whether rhesus monkeys ( Macaca mulatta) are capable of a simple form of metacognitive access to the contents of short-term memory. Monkeys chose among four opaque tubes, one of which concealed food. The tube containing the reward varied randomly from trial to trial. On half the trials the monkeys observed the experimenter baiting the tube, whereas on the remaining trials their view of the baiting was blocked. On each trial, monkeys were allowed a single chance to select the tube containing the reward. During the choice period the monkeys had the opportunity to look down the length of each tube, to determine if it contained food. When they knew the location of the reward, most monkeys chose without looking. In contrast, when ignorant, monkeys often made the effort required to look, thereby learning the location of the reward before choosing. Looking improved accuracy on trials on which monkeys had not observed the baiting. The difference in looking behavior between trials on which the monkeys knew, and trials on which they were ignorant, suggests that rhesus monkeys discriminate between knowing and not knowing. This result extends similar observations made of children and apes to a species of Old World monkey, suggesting that the underlying cognitive capacities may be widely distributed among primates.

  9. 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

    2016-01-01

    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.

  10. Sidiming attenuates morphine withdrawal syndrome and nitric oxide (synthase) levels in morphine-dependent rats and rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    Zheng Yang; Renbin Huang; Jianchun Huang; Shijun Zhang; Xing Lin; Yang Jiao; Weizhe Jiang

    2011-01-01

    The present study analyzed the effects of Sidiming, a Chinese herbal compound, on withdrawal syndrome, body weight loss, and serum levels of nitric oxide and its synthase in morphine- dependent rats and rhesus monkeys. These effects were compared with clonidine, an active control drug used for clinical treatment. Results showed that 4 and 8 g/kg Sidiming, respectively, significantly suppressed morphine withdrawal syndrome and reduced body mass loss in morphine-dependent rats. In addition, 2.4 and 4.8 g/kg Sidiming, respectively, significantly attenuated withdrawal syndrome in rhesus monkeys. High-dose Sidiming (8 g/kg in rats and 4.8 g/kg in rhesus monkeys) led to significantly inhibited serum levels of nitric oxide and its synthase in morphine-dependent rats and rhesus monkeys, which were greater than clonidine. These findings suggested that Sidiming treatment attenuated withdrawal syndrome in morphine-dependent rats and rhesus monkeys by inhibiting serum nitric oxide and its synthase.

  11. Stereotaxic coordinates for the Rhesus monkey thalamus and mesencephalon referencing visual afferents and cytoarchitecture.

    Science.gov (United States)

    Benevento, L A

    1975-01-01

    When using a stereotaxic instrument for visual field stimulation we found that electrode placements in the thalamus and mesencephalon of prone rhesus monkeys with the aid of avaiable atlases showed considerable errors. As these animals are valuable for primate visual system reseach an atlas was constructed with methods that have not been used before for rhesus. In addition, the specific connections from the visual cortices, superior colliculus and retina to the thalamus and mesencephalon are also shown. Anesthetized monkeys of specific body dimensions had a matrix of pins inserted into the brain before fixation. A matrix was used so that the penetrations seen in the sectioned brain could be cross related as a control for accurate measurements of the stereotaxic planes throughout the brain. The surface of the whole brain frozen blocks were photographed on the microtome just before a cut section was taken. These calibrated pictures formed the "floor plan" of the atlas as they represent more accurately the brain geometry than individual sections which are distorted by cutting, staining and mounting. Cytoarchitectural (Nissl stain) and axonal connectional (Fink-Heimer stain) information was transferred and adjusted onto the block pictures from their corresponding stained sections. Follow up experiments showed that the present coordinates are accurate for these monkeys of restricted body dimensions. In addition, referencing visual axonal projections onto the same cytoarchitectural map in stereotaxic coordinates provides an atlas for localizing areas of the thalamus, on a basis other than cytoarchitecture, which receive combinations of visual inputs for further anatomical and physiological studies of the rhesus monkey visual system. The atlas further demonstrates that projections do not necessarily follow the cytoarchitectural definition of an area, but rather redefine the thalamus on the basis of specific axonal connections.

  12. Effects of pirenzepine on pupil size and accommodation in rhesus monkeys.

    Science.gov (United States)

    Ostrin, Lisa A; Frishman, Laura J; Glasser, Adrian

    2004-10-01

    Pirenzepine is suggested to be a relatively selective muscarinic (M(1)) antagonist and is currently under investigation for the treatment of myopia. Atropine, a nonselective M-type antagonist, is used in the treatment of myopia, but has undesired ocular and systemic side effects. An M(1)-specific antagonist may decrease side effects and remain effective at reducing the progression of myopia. In the current study, the effects of pirenzepine on pupil diameter, resting refraction, and accommodation were studied in rhesus monkeys. The time course and extent of mydriasis from subconjunctival injection of 2% pirenzepine were determined in five normal rhesus monkeys, and the effects on static and dynamic accommodation were determined in four rhesus monkeys with permanent indwelling electrodes in the Edinger-Westphal (EW) nucleus of the midbrain. Subconjunctival injections of 0.0002% to 0.2% pirenzepine in log unit dilutions were tested in three monkeys to determine the effects on static EW-stimulated accommodation. At 40 to 50 minutes after pirenzepine injection, accommodation was stimulated pharmacologically in both eyes, and the response was measured for 30 minutes. After 2% pirenzepine injection, pupil size increased 2.02 +/- 0.41 mm, there was a hyperopic shift in resting refraction of 1.07 +/- 0.23 D, and nearly complete cycloplegia occurred. Maximum EW-stimulated accommodation was significantly decreased 20 to 40 minutes after 0.02% or greater pirenzepine. Carbachol-stimulated accommodation was significantly decreased after 0.2% or greater pirenzepine. Subconjunctival injections of 0.02% or greater pirenzepine result in a significant decrease in accommodation and are probably acting through nonselective muscarinic antagonism. Subconjunctival injections of 0.002% or less pirenzepine do not decrease EW-stimulated accommodation.

  13. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study.

    Science.gov (United States)

    Mattison, Julie A; Roth, George S; Beasley, T Mark; Tilmont, Edward M; Handy, April M; Herbert, Richard L; Longo, Dan L; Allison, David B; Young, Jennifer E; Bryant, Mark; Barnard, Dennis; Ward, Walter F; Qi, Wenbo; Ingram, Donald K; de Cabo, Rafael

    2012-09-13

    Calorie restriction (CR), a reduction of 10–40% in intake of a nutritious diet, is often reported as the most robust non-genetic mechanism to extend lifespan and healthspan. CR is frequently used as a tool to understand mechanisms behind ageing and age-associated diseases. In addition to and independently of increasing lifespan, CR has been reported to delay or prevent the occurrence of many chronic diseases in a variety of animals. Beneficial effects of CR on outcomes such as immune function, motor coordination and resistance to sarcopenia in rhesus monkeys have recently been reported. We report here that a CR regimen implemented in young and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes. Our findings contrast with an ongoing study at the Wisconsin National Primate Research Center (WNPRC), which reported improved survival associated with 30% CR initiated in adult rhesus monkeys (7–14 years) and a preliminary report with a small number of CR monkeys. Over the years, both NIA and WNPRC have extensively documented beneficial health effects of CR in these two apparently parallel studies. The implications of the WNPRC findings were important as they extended CR findings beyond the laboratory rodent and to a long-lived primate. Our study suggests a separation between health effects, morbidity and mortality, and similar to what has been shown in rodents, study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate.

  14. 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…

  15. 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…

  16. 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.

  17. Assessing significant (>30%) alopecia as a possible biomarker for stress in captive rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Novak, Melinda A; Menard, Mark T; El-Mallah, Saif N; Rosenberg, Kendra; Lutz, Corrine K; Worlein, Julie; Coleman, Kris; Meyer, Jerrold S

    2017-01-01

    Hair loss is common in macaque colonies. Very little is known about the relationship between psychological stress and hair loss. We initially examined alopecia and hair cortisol concentrations in 198 (89 male) rhesus macaques from three primate centers and demonstrated replicability of our previous finding that extensive alopecia (>30% hair loss) is associated with increased chronic cortisol concentrations and significantly affected by facility. A subset of these monkeys (142 of which 67 were males) were sampled twice approximately 8 months apart allowing us to examine the hypotheses that gaining hair should be associated with decreases in cortisol concentrations and vice versa. Hair loss was digitally scored using ImageJ software for the first sample. Then visual assessment was used to examine the second sample, resulting in three categories of coat condition: (i) monkeys that remained fully haired; (ii) monkeys that remained alopecic (with more than 30% hair loss); or (iii) monkeys that showed more than a 15% increase in hair. The sample size for the group that lost hair was too small to be analyzed. Consistent with our hypothesis, monkeys that gained hair showed a significant reduction in hair cortisol concentrations but this effect only held for females. Coat condition changed little across sampling periods with only 25 (11 male) monkeys showing a greater than 15% gain of hair. Twenty (7 male) monkeys remained alopecic, whereas 97 (49 males) remained fully haired. Hair cortisol was highly correlated across samples for the monkeys that retained their status (remained alopecic or retained their hair). Am. J. Primatol. 79:e22547, 2017. © 2016 Wiley Periodicals, Inc.

  18. 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.

  19. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, K.L.; Chang, M.N.; Chabala, J.C.; Chiu, S.H.; Eline, D.; Hucker, H.B.; Sweeney, B.M.; White, S.D.; Arison, B.H.; Smith, J.L.

    1988-09-01

    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. Rhesus monkeys show human-like changes in gaze following across the lifespan.

    Science.gov (United States)

    Rosati, Alexandra G; Arre, Alyssa M; Platt, Michael L; Santos, Laurie R

    2016-05-11

    Gaze following, or co-orienting with others, is a foundational skill for human social behaviour. The emergence of this capacity scaffolds critical human-specific abilities such as theory of mind and language. Non-human primates also follow others' gaze, but less is known about how the cognitive mechanisms supporting this behaviour develop over the lifespan. Here we experimentally tested gaze following in 481 semi-free-ranging rhesus macaques (Macaca mulatta) ranging from infancy to old age. We found that monkeys began to follow gaze in infancy and this response peaked in the juvenile period-suggesting that younger monkeys were especially attuned to gaze information, like humans. After sexual maturity, monkeys exhibited human-like sex differences in gaze following, with adult females showing more gaze following than males. Finally, older monkeys showed reduced propensity to follow gaze, just as older humans do. In a second study (n = 80), we confirmed that macaques exhibit similar baseline rates of looking upwards in a control condition, regardless of age. Our findings indicate that-despite important differences in human and non-human primate life-history characteristics and typical social experiences-monkeys undergo robust ontogenetic shifts in gaze following across early development, adulthood and ageing that are strikingly similar to those of humans.

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

    Science.gov (United States)

    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. 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

  3. 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.

  4. Effects of Head-down Tilt on Nerve Conduction in Rhesus Monkeys

    Science.gov (United States)

    Sun, Bo; Zhang, Xiao-Yun; Liu, Li-Zhi; Chen, Zhao-Hui; Dai, Zhong-Quan; Huang, Xu-Sheng

    2017-01-01

    Background: Few studies have focused on peripheral nerve conduction during exposure to microgravity. The −6° head-down tilt (HDT) comprises an experimental model used to simulate the space flight environment. This study investigated nerve conduction characteristics of rhesus monkeys before and after prolonged exposure to HDT. Methods: Six rhesus monkeys (3–4 years old) were tilted backward 6° from the horizontal. Nerve conduction studies (NCSs) were performed on the median, ulnar, tibial, and fibular motor nerves. Analysis of variance with a randomized block design was conducted to compare the differences in the NCS before and 7, 21, and 42 days after the −6° HDT. Results: The proximal amplitude of the CMAP of the median nerve was significantly decreased at 21 and 42 days of HDT compared with the amplitude before HDT (4.38 ± 2.83 vs. 8.40 ± 2.66 mV, F = 4.85, P = 0.013 and 3.30 ± 2.70 vs. 8.40 ± 2.66 mV, F = 5.93, P = 0.004, respectively). The distal amplitude of the CMAP of the median nerve was significantly decreased at 7, 21, and 42 days of HDT compared with the amplitude before HDT (7.28 ± 1.27 vs. 10.25 ± 3.40 mV, F = 4.03, P = 0.039; 5.05 ± 2.01 vs. 10.25 ± 3.40 mV, F = 6.25, P = 0.04; and 3.95 ± 2.79 vs. 10.25 ± 3.40 mV, F = 7.35, P = 0.01; respectively). The proximal amplitude of the CMAP of the tibial nerve was significantly decreased at 42 days of HDT compared with the amplitude before HDT (6.14 ± 1.94 vs. 11.87 ± 3.19 mV, F = 5.02, P = 0.039). Conclusions: This study demonstrates that the compound muscle action potential amplitudes of nerves are decreased under simulated microgravity in rhesus monkeys. Moreover, rhesus monkeys exposed to HDT might be served as an experimental model for the study of NCS under microgravity. PMID:28139516

  5. A novel kindling model of temporal lobe epilepsy in rhesus monkeys induced by Coriaria lactone.

    Science.gov (United States)

    Hong, Zhen; Yang, Tian-Hua; Tang, Ming-Hai; Zhang, Heng; Li, Hong-Xia; Chen, Lei; Chen, Qin; Zhou, Dong

    2013-12-01

    One of the major challenges in developing novel therapeutics for human epileptic disorders derives from the limitation of knowledge of the processes by which epilepsy is generated (epileptogenesis). Furthermore, the inability to obtain human samples at the early stage of epilepsy hinders studies designed to further understand epileptogenesis. Thus, an effective animal model is critical for studies investigating this process. The purpose of this study was to establish a new primate kindling model of temporal lobe epilepsy (TLE) as an animal model of epileptogenesis. Here, repeated injections of Coriaria lactone (CL) at a subthreshold dose elicited partial seizures that culminated in secondarily generalized tonic-clonic seizures. The sequence of events and features of the behaviors observed in this model simulated those observed in human TLE. Electroencephalogram monitoring revealed the temporal lobe origins of the epileptiform potentials, which were consistent with the behavioral changes observed. A total of 7 rhesus monkeys (78%) were kindled with a median of 48 (41 to 60) CL injections. Both the seizure-induction and mortality rates were dose-dependent. A CL injection at 1.50mg/kg showed the lowest animal mortality rate (0%) and the highest seizure-induction rate (100%). Extensive kindling by CL injections with a median of 97 injections (overkindling) subsequently resulted in the recurrence of spontaneous seizures in rhesus monkeys with frequency patterns that were similar to those observed in human TLE. In addition, rhesus monkeys subjected to large numbers of kindling stimuli displayed mitochondrial damage and astrocyte activation in a pattern that was similar to the neuropathological changes characteristic of human TLE. Thus, a kindling TLE model in rhesus monkeys representing a primate animal model of epileptogenesis was established for the first time using repeated intramuscular injections of Coriaria lactone. This model was easily and efficiently performed

  6. Asymmetry of attentional set in rhesus monkeys learning colour and shape discriminations

    OpenAIRE

    Baxter, Mark G.; Gaffan, David

    2006-01-01

    We trained rhesus monkeys on six visual discrimination problems using stimuli that varied in both shape and colour. For one group of animals shape was always relevant in these six problems, and colour always irrelevant, and for the other animals vice versa. During these “intradimensional shifts” (ID) the problems were learned at equal rates by the two groups, shape-relevant and colour-relevant. We then trained three further problems in which the other dimension was now relevant (“extradimensi...

  7. Aberrant genomic imprinting in rhesus monkey embryonic stem cells.

    Science.gov (United States)

    Fujimoto, Akihisa; Mitalipov, Shoukhrat M; Kuo, Hung-Chih; Wolf, Don P

    2006-03-01

    Genomic imprinting involves modification of a gene or a chromosomal region that results in the differential expression of parental alleles. Disruption or inappropriate expression of imprinted genes is associated with several clinically significant syndromes and tumorigenesis in humans. Additionally, abnormal imprinting occurs in mouse embryonic stem cells (ESCs) and in clonally derived animals. Imprinted gene expression patterns in primate ESCs are largely unknown, despite the clinical potential of the latter in the cell-based treatment of human disease. Because of the possible implications of abnormal gene expression to cell or tissue replacement therapies involving ESCs, we examined allele specific expression of four imprinted genes in the rhesus macaque. Genomic and complementary DNA from embryos and ESC lines containing useful single nucleotide polymorphisms were subjected to polymerase chain reaction-based amplification and sequence analysis. In blastocysts, NDN expression was variable indicating abnormal or incomplete imprinting whereas IGF2 and SNRPN were expressed exclusively from the paternal allele and H19 from the maternal allele as expected. In ESCs, both NDN and SNRPN were expressed from the paternal allele while IGF2 and H19 showed loss of imprinting and biallelic expression. In differentiated ESC progeny, these expression patterns were maintained. The implications of aberrant imprinted gene expression to ESC differentiation in vitro and on ESC-derived cell function in vivo after transplantation are unknown.

  8. 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.

  9. Effects of confined space and near vision stimulation on refractive status and vitreous chamber depth in adolescent rhesus monkeys.

    Science.gov (United States)

    Leng, Yunxia; Lan, Weizhong; Yu, Keming; Liu, Bingqian; Yang, Zhikuan; Li, Zheng; Zhong, Xingwu; Zhang, Shaochong; Ge, Jian

    2010-12-01

    This study aimed to investigate the effects of sustained near vision stimulation, on the refractive development and elongation of the vitreous chamber in adolescent rhesus monkeys. A total of 12 adolescent rhesus monkeys (1.5-2.0 years old) were randomly assigned to 3 groups. In groups A (n=4) and B (n=4), monkeys were reared in close-vision cages for 8 and 4 h d(-1), respectively; tiny granules were added on the cage floor to avoid visual deprivation and to encourage near gaze. In group C (n=4), monkeys were reared in open-vision cages, with non-granule food as a control. Vitreous chamber depth, refractive status, and corneal refractive power were assessed over 18 months. Paired t-test was used to compare the differences and a P-valuemonkeys. Our results demonstrate the potential for a primate model of near-work-related myopia.

  10. Experience-dependent changes in the development of face preferences in infant rhesus monkeys.

    Science.gov (United States)

    Parr, Lisa A; Murphy, Lauren; Feczko, Eric; Brooks, Jenna; Collantes, Marie; Heitz, Thomas R

    2016-12-01

    It is well known that early experience shapes the development of visual perception for faces in humans. However, the effect of experience on the development of social attention in non-human primates is unknown. In two studies, we examined the effect of cumulative social experience on developmental changes in attention to the faces of unfamiliar conspecifics or heterospecifics, and mom versus an unfamiliar female. From birth, infant rhesus monkeys preferred to look at conspecific compared to heterospecific faces, but this pattern reversed over time. In contrast, no consistent differences were found for attention to mom's face compared to an unfamiliar female. These results suggest differential roles of social experience in shaping the development of face preferences in infant monkeys. Results have important implications for establishing normative trajectories for the development of face preferences in an animal model of human social behavior. © 2016 Wiley Periodicals, Inc.

  11. Cloning of a novel inhibin alpha cDNA from rhesus monkey testis

    Directory of Open Access Journals (Sweden)

    Woodruff Teresa K

    2004-10-01

    Full Text Available Abstract Background Inhibins are dimeric gonadal protein hormones that negatively regulate pituitary FSH synthesis and secretion. Inhibin B is produced by testicular Sertoli cells and is the primary circulating form of inhibin in most adult male mammals. Inhibin B is comprised of the inhibin alpha subunit disulfide-linked to the inhibin/activin betaB subunit. Here we describe the cloning of the cDNAs encoding these subunits from adult rhesus monkey testis RNA. Methods The subunit cDNAs were cloned by a combination of reverse transcriptase polymerase chain reaction (RT-PCR and 5' rapid amplification of cDNA ends (RACE RT-PCR from adult rhesus monkey testis RNA. Results Both the inhibin alpha and betaB subunit nucleotide and predicted protein sequences are highly conserved with other mammalian species, particularly with humans. During the course of these investigations, a novel inhibin alpha mRNA isoform was also identified. This form, referred to as rhesus monkey inhibin alpha-variant 2, appears to derive from both alternative transcription initiation as well as alternative splicing. rmInhibin alpha-variant 2 is comprised of a novel 5' exon (exon 0, which is spliced in-frame with exon 2 of the conventional inhibin alpha isoforms (variant 1. Exon 1 is skipped in its entirety such that the pro-alpha and part of the alpha N regions are not included in the predicted protein. rmInhibin alpha -variant 2 is of relatively low abundance and its biological function has not yet been ascertained. Conclusion The data show that the predicted inhibin B protein is very similar between monkeys and humans. Therefore, studies in monkeys using recombinant human inhibins are likely to reflect actions of the homologous ligands. In addition, we have observed the first inhibin alpha subunit mRNA variant. It is possible that variants will be observed in other species as well and this may lead to novel insights into inhibin action.

  12. [Pharmacokinetics of salvianolic acid A after single intravenous administration in Rhesus monkey].

    Science.gov (United States)

    Song, Jun-ke; Zhang, Wen; Zhang, Wei-ku; Feng, Zhang-ying; Xie, Tao; Du, Guan-Hua

    2015-09-01

    Salvianolic acid A (Sal A) is one of the most effective compounds isolated from the root of Salvia miltiorrhiza. Up to now, several studies regarding the pharmacokinetic profiles of Sal A have been reported, however there is no such study reported in monkeys, the species which is more similar to human. The aim of this study is to develop a LC-MS method for the determination of Sal A in monkey plasma and apply it to the pharmacokinetic studies of monkeys. After single intravenous administration of Sal A, the plasma concentration-time curves were observed and the main pharmacokinetic parameters were calculated. The plasma concentration at 2 min (C2 (min)) values were (28.343 ± 6.426), (45.679 ± 12.301) and (113.293 ± 24.360) mg x L(-1) for Rhesus monkeys treated with Sal A at 2.5, 5 and 10 mg x kg(-1). The area under the concentration-time curve (AUC(0-∞)) values were (3.316 ± 0.871), (5.754 ± 2.150) and (13.761 ± 2.825) μg x L(-1) x h, respectively. Furthermore, this method was improved and applied to the simultaneous determination of Sal A, Sal B and Sal C, which provided useful information for preclinical studies and clinical trials of Sal A, Sal B and Sal C.

  13. Urinary excretion of cortisol from rhesus monkeys (Macaca mulatta) habituated to restraint

    Science.gov (United States)

    Wade, C. E.; Ortiz, R. M.

    1997-01-01

    Use of monkeys in research has often required that they be restrained in a chair. However, chair restraint can elicit an initial neuroendocrine stress response. Also, inactivity associated with restraint can induce muscular atrophy. We proposed that prior habituation of monkeys to chair restraint would attenuate these neuroendocrine responses without causing substantial muscle wasting. Four rhesus monkeys (Macaca mulatta) were trained and habituated to a restraint chair specifically designed for spaceflight. During the study, monkeys were placed in metabolic cages for 7 days (prerestraint, Phase I), placed in a chair restraint for 18 days (Phase II), and then returned to their metabolic cages for 5 days (postrestraint, Phase III). Urine was collected between 0700-1100 daily, and measurements of cortisol, creatinine, and electrolyte concentrations were adjusted for hourly excretion rates. Body weights of the monkeys did not change between start of the prerestraint and postrestraint phases (10.3 +/- 0.8 vs. 10.3 +/- 0.9 kg, respectively). During the 3 phases, mean excretion rate of cortisol did not change (24.1 +/- 10.3, 26.7 +/- 7.7, and 19.3 +/- 5.8 microg/h, respectively). Mean excretion rate of creatinine (37.3 +/- 7.5, 37.5 +/- 12.2, and 36.9 +/- 17.1 mg/h, respectively), Na+ (3.3 +/- 1.2, 3.2 +/- 1.2, 2.2 +/- 1.8 mmol/h, respectively), and K+ (5.3 +/- 1.8, 5.4 +/- 1.6, and 4.3 +/- 2.8 mmol/h, respectively) were also not altered. Lack of an increase in excreted urinary cortisol suggested that prior habituation to chair restraint attenuated neuroendocrine responses reported previously. Also, the chair restraint method used appeared to allow adequate activity, because the monkeys did not have indices of muscle wasting.

  14. Rhesus Monkeys (Macaca Mulatta) Demonstrate Robust Memory for What and Where, but Not When, in an Open-Field Test of Memory

    Science.gov (United States)

    Hampton, R.R.; Hampstead, B.M.; Murray, E.A.

    2005-01-01

    We adapted a paradigm developed by Clayton and Dickinson (1998), who demonstrated memory for what, where, and when in scrub jays, for use with rhesus monkeys. In the study phase of each trial, monkeys found a preferred and a less-preferred food reward in a trial-unique array of three locations in a large room. After 1h, monkeys returned to the…

  15. Do you see what I see? A comparative investigation of the Delboeuf illusion in humans (Homo sapiens), rhesus monkeys (Macaca mulatta), and capuchin monkeys (Cebus apella).

    Science.gov (United States)

    Parrish, Audrey E; Brosnan, Sarah F; Beran, Michael J

    2015-10-01

    Studying visual illusions is critical to understanding typical visual perception. We investigated whether rhesus monkeys (Macaca mulatta) and capuchin monkeys (Cebus apella) perceived the Delboeuf illusion in a similar manner as human adults (Homo sapiens). To test this, in Experiment 1, we presented monkeys and humans with a relative discrimination task that required subjects to choose the larger of 2 central dots that were sometimes encircled by concentric rings. As predicted, humans demonstrated evidence of the Delboeuf illusion, overestimating central dots when small rings surrounded them and underestimating the size of central dots when large rings surrounded them. However, monkeys did not show evidence of the illusion. To rule out an alternate explanation, in Experiment 2, we presented all species with an absolute classification task that required them to classify a central dot as "small" or "large." We presented a range of ring sizes to determine whether the Delboeuf illusion would occur for any dot-to-ring ratios. Here, we found evidence of the Delboeuf illusion in all 3 species. Humans and monkeys underestimated central dot size to a progressively greater degree with progressively larger rings. The Delboeuf illusion now has been extended to include capuchin monkeys and rhesus monkeys, and through such comparative investigations we can better evaluate hypotheses regarding illusion perception among nonhuman animals.

  16. The socioendocrinology of adolescent development in male rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Dixson, A F; Nevison, C M

    1997-04-01

    Observations were made on four captive breeding groups of rhesus monkeys in order to measure hormonal, behavioral, and genital changes in adolescent males during the annual mating season. Three questions were addressed with regard to possible effects of social environment upon reproductive maturation: (1) Does male agonistic rank influence adolescent development? (2) Does affiliation between adolescent males and adult females during the mating season influence the males' reproductive development? (3) Does maternal rank exert any effect upon reproductive maturation in adolescent sons? In many (but not all) cases male rank was positively correlated with circulating testosterone and testes weights during the mating season. Affiliative behavior (allogrooming and sexual interactions) between adolescents and adult females in their social groups bore no relationship to the degree of reproductive maturation in males. Mounts involving intromission were infrequent, but sons of high-ranking mothers gained significantly more intromissions than sons of lower-ranking females. Maternal rank was also found to correlate with circulating testosterone levels, testes weights, growth of the baculum (os penis), and maintenance of body weight in adolescent sons during the mating season. By contrast, levels of beta-endorphin in the cerebrospinal fluid of adolescent males did not correlate with social rank, testosterone levels, or genital development. These findings point to possible effects of maternal rank, as well as intermale agonistic rank, in determining reproductive maturation during adolescence in the male rhesus monkey.

  17. Neurotoxin-Induced Catecholaminergic Loss in the Colonic Myenteric Plexus of Rhesus Monkeys

    Science.gov (United States)

    Shultz, Jeanette M; Resnikoff, Henry; Bondarenko, Viktorya; Joers, Valerie; Mejia, Andres; Simmons, Heather; Emborg, Marina E

    2017-01-01

    Objective Constipation is a common non-motor symptom of Parkinson’s disease (PD). Although pathology of the enteric nervous system (ENS) has been associated with constipation in PD, the contribution of catecholaminergic neurodegeneration to this symptom is currently debated. The goal of this study was to assess the effects of the neurotoxin 6-hydroxydopamine (6-OHDA) on the colonic myenteric plexus and shed light on the role of catecholaminergic innervation in gastrointestinal (GI) function. Methods Proximal colon tissue from 6-OHDA-treated (n=5) and age-matched control (n=5) rhesus monkeys was immunostained and quantified using ImageJ software. All animals underwent routine daily feces monitoring to assess for constipation or other GI dysfunction. Results Quantification of tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC)-immunoreactivity (-ir) revealed significant reduction in myenteric ganglia of 6-OHDA-treated animals compared to controls (TH-ir: 87.8%, P30% days) soft stool or diarrhea in 2 of the 5 6-OHDA-treated animals and 0 of the 5 control animals during the 2 months prior to necropsy, with no animals exhibiting signs of constipation. Conclusion Systemic administration of 6-OHDA to rhesus monkeys significantly reduced catecholaminergic expression in the colonic myenteric plexus without inducing constipation. These findings support the concept that ENS catecholaminergic loss is not responsible for constipation in PD. PMID:28090391

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

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    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.

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

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    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.

  20. 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.

  1. Characteristics of diffusion-tensor imaging for healthy adult rhesus monkey brains

    Institute of Scientific and Technical Information of China (English)

    Xinxiang Zhao; Jun Pu; Yaodong Fan; Xiaoqun Niu; Danping Yu; Yanglin Zhang

    2013-01-01

    Diffusion-tensor imaging can be used to observe the microstructure of brain tissue. Fractional sotropy reflects the integrity of white matter fibers. Fractional anisotropy of a young adult brain is low in gray matter, high in white matter, and highest in the splenium of the corpus cal osum. Thus, we selected the anterior and posterior limbs of the internal capsule, head of the caudate nucleus, se-mioval center, thalamus, and corpus cal osum (splenium and genu) as regions of interest when using diffusion-tensor imaging to observe fractional anisotropy of major white matter fiber tracts and the deep gray matter of healthy rhesus monkeys aged 4-8 years. Results showed no laterality ferences in fractional anisotropy values. Fractional anisotropy values were low in the head of date nucleus and thalamus in gray matter. Fractional anisotropy values were highest in the sple-nium of corpus cal osum in the white matter, fol owed by genu of the corpus cal osum and the posterior limb of the internal capsule. Fractional anisotropy values were lowest in the semioval center and posterior limb of internal capsule. These results suggest that fractional anisotropy values in major white matter fibers and the deep gray matter of 4-8-year-old rhesus monkeys are similar to those of healthy young people.

  2. Ultrastructural evidence for impaired mitochondrial fission in the aged rhesus monkey dorsolateral prefrontal cortex.

    Science.gov (United States)

    Morozov, Yury M; Datta, Dibyadeep; Paspalas, Constantinos D; Arnsten, Amy F T

    2017-03-01

    Dorsolateral prefrontal cortex mediates high-order cognitive functions that are impaired early in the aging process in monkeys and humans. Here, we report pronounced changes in mitochondrial morphology in dendrites of dorsolateral prefrontal cortex neurons from aged rhesus macaques. Electron microscopy paired with 3D reconstruction from serial sections revealed an age-related increase in mitochondria with thin segments that intermingled with enlarged ones, the 'mitochondria-on-a-string' phenotype, similar to those recently reported in patients with Alzheimer's disease. The thin mitochondrial segments were associated with endoplasmic reticulum cisterns, and the mitochondrial proteins Fis1 and Drp1, all of which initiate mitochondrial fission. These data suggest that the 'mitochondria-on-a-string' phenotype may reflect malfunction in mitochondrial dynamics, whereby fission is initiated, but the process is incomplete due to malfunction of subsequent step(s). Thus, aged rhesus monkeys may be particularly helpful in exploring the age-related changes that render higher cortical circuits so vulnerable to degeneration.

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

    Science.gov (United States)

    Wang, Yong; Ding, Hui; Stell, William K; Liu, Liangping; Li, Saiqun; Liu, Hongshan; Zhong, Xingwu

    2015-01-01

    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; Pexposure to natural outdoor light might have an effect to reduced hyperopic defocus-induced myopia. Also, the data imply that early life exposure to sunlight may

  4. Evaluation in Rhesus Monkeys of a Bivalent Live Attenuated Dengue Vaccine Containing Types 2 and 4 Viruses.

    Science.gov (United States)

    1984-06-01

    previous reports,(1) antibody levels of most of the vaccinated animals declined markedly on or before post vacination day 150. PR13s showed that the EM-4...V.H., Gould, D.J., Chapple, F.E., and Russell, P.K.: Dengue 2 vacine , viremia and Inmune response in rhesus monkeys. Infect. Immun. 27, 181-186, 1980. 2

  5. Comparison between carbachol iontophoresis and intravenous pilocarpine stimulated accommodation in anesthetized rhesus monkeys.

    Science.gov (United States)

    Wendt, Mark; He, Lin; Glasser, Adrian

    2013-10-01

    Rhesus monkeys are an animal model for human accommodation and presbyopia and consistent and repeatable methods are needed to stimulate and measure accommodation in anesthetized rhesus monkeys. Accommodation has typically been pharmacologically stimulated with topical pilocarpine or carbachol iontophoresis. Intravenous (i.v.) pilocarpine has recently been shown to produce more natural, rapid and reproducible accommodative responses compared to topical pilocarpine. Here, i.v. pilocarpine was compared to carbachol iontophoresis stimulated accommodation. Experiments were performed under anaesthesia on five previously iridectomized monkeys aged 10-16 years. In three monkeys, accommodation was stimulated with carbachol iontophoresis in five successive experiments and refraction measured with a Hartinger coincidence refractometer. In separate experiments, accommodation was stimulated using a 5 mg/kg bolus of i.v. pilocarpine given over 30 s followed by a continuous infusion of 20 mg/kg/hr for 5.5 min in three successive experiments with the same monkeys as well as in single experiments with two additional monkeys. Refraction was measured continuously using photorefraction with baseline and accommodated refraction also measured with the Hartinger. In subsequent i.v. pilocarpine experiments with each monkey, accommodative changes in lens equatorial diameter were measured in real-time with video-image analysis. Maximum accommodation of three monkeys with carbachol iontophoresis (five repeats) was (mean ± SD; range) 14.0 ± 3.5; 9.9-20.3 D and with i.v. pilocarpine stimulation (three repeats) was 11.1 ± 1.1; 9.9-13.0 D. The average of the standard deviations of maximum accommodation from each monkey was 0.8 ± 0.3 D from carbachol iontophoresis and 0.3 ± 0.2 from i.v. pilocarpine. The average latency to the start of the response after carbachol iontophoresis was 2.5 ± 3.9; 0.0-12.0 min with a time constant of 12.7 ± 9.5; 2.3-29.2 min. The average

  6. Shallow discounting of delayed cocaine by male rhesus monkeys when immediate food is the choice alternative.

    Science.gov (United States)

    Huskinson, Sally L; Myerson, Joel; Green, Leonard; Rowlett, James K; Woolverton, William L; Freeman, Kevin B

    2016-12-01

    Huskinson et al. (2015) recently examined delay discounting in monkeys choosing between an immediate drug (cocaine) reinforcer and a delayed nondrug (food) reinforcer. The present experiment examined the reverse situation: choice between immediate nondrug (food) and delayed drug (cocaine) reinforcers. Whereas the former choice situation exemplifies drug abuse from a delay-discounting perspective, our interest in the latter choice situation is derived from the observation that drug abusers, who characteristically are associated with impulsive choice, typically must devote considerable time to procuring drugs, often at the expense of immediate nondrug alternatives. Accordingly, we analyzed 3 male rhesus monkeys' choices between immediate food and delayed cocaine (0.1 and 0.2 mg/kg/injection) using a hyperbolic model that allowed us to compare discounting rates between qualitatively different reinforcers. Choice of immediate food increased with food amount, and choice functions generally shifted leftward as delay to cocaine increased, indicating a decrease in the subjective value of cocaine. Compared with our previous delay-discounting experiment with immediate cocaine versus delayed food, both doses of delayed cocaine were discounted at a shallow rate. The present results demonstrate that rhesus monkeys will tolerate relatively long delays in an immediate-food versus delayed-drug situation, suggesting that in intertemporal choices between cocaine and food, the subjective value of cocaine is less affected by the delay until reinforcement than is the subjective value of delayed food. More generally, the present findings suggest that although drug abusers may choose impulsively when immediate drug reinforcement is available, they exercise self-control in the acquisition of a highly preferred, delayed drug reinforcer. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  7. Effect of mother's dominance rank on offspring temperament in infant rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Suarez-Jimenez, Benjamin; Hathaway, Amanda; Waters, Carlos; Vaughan, Kelli; Suomi, Stephen J; Noble, Pamela L; Pine, Daniel S; Fox, Nathan A; Nelson, Eric E

    2013-01-01

    In humans, temperament plays an important role in socialization and personality. Some temperaments, such as behavioral inhibition are associated with an increased risk for psychopathology. Nonhuman primates can serve as a model for neurobiological and developmental contributions to emotional development and several recent studies have begun to investigate temperament in nonhuman primates. In rhesus monkeys, dominance rank is inherited from the mother and is associated with social and emotional tendencies that resemble differences in temperament. The current study assessed differences in temperament in infant rhesus monkeys as a function of maternal dominance rank. Temperament was assessed in 26 infants (13 males) from birth until 6 months of age with a battery that included Brazelton test, human intruder test, human intruder-startle, cortisol stress reactivity, and home cage observations of interactions with peers and the mother. Throughout testing, infants lived with their mothers and a small group of other monkeys in indoor/outdoor runs. Dominance rank of the mothers within each run was rated as either low/middle (N = 18, 9 male) or high/alpha (N = 8, 4 female). Infants of high-ranking mothers displayed more intruder-directed aggression and reduced startle potentiation in the human intruder tests. Dominant offspring also had reduced levels cortisol and startle across development and spent more time away from mothers in the interaction tests. These results suggest that dominance of the mother may be reflected in behavioral reactivity of infants early in life. These findings set up future studies, which may focus on contributing factors to both dominance and temperament such as genetics, rearing, and socialization. Such factors are likely to interact across development in meaningful ways. These results also suggest future human-based studies of a similar relationship may be warranted, although social dominance is clearly more complex in human than macaque societies.

  8. Rhesus Monkeys (Macaca mulatta) and Capuchin Monkeys (Cebus apella) Remember Future Responses in a Computerized Task

    Science.gov (United States)

    Beran, Michael J.; Evans, Theodore A.; Klein, Emily D.; Einstein, Gilles O.

    2012-01-01

    Planning is an important aspect of many daily activities for humans. Planning involves forming a strategy in anticipation of a future need. However, evidence that nonhuman animals can plan for future situations is limited, particularly in relation to the many other kinds of cognitive capacities that they appear to share with humans. One critical aspect of planning is the ability to remember future responses, or what is called prospective coding. Two monkey species performed a series of computerized tasks that required encoding a future response at the outset of each trial. Monkeys of both species showed competence in all tests that were given, providing evidence that they anticipated future responses, and that they appropriately engaged in those responses when the time was right for such responses. In addition, some tests demonstrated that monkeys even remembered future responses that were not as presently motivating as were other aspects of the task environment. These results indicated that monkeys can anticipate future responses and retain and implement those responses when appropriate. PMID:22545901

  9. Ranking Cognitive Flexibility in a Group Setting of Rhesus Monkeys with a Set-Shifting Procedure

    Science.gov (United States)

    Shnitko, Tatiana A.; Allen, Daicia C.; Gonzales, Steven W.; Walter, Nicole A. R.; Grant, Kathleen A.

    2017-01-01

    Attentional set-shifting ability is an executive function underling cognitive flexibility in humans and animals. In humans, this function is typically observed during a single experimental session where dimensions of playing cards are used to measure flexibility in the face of changing rules for reinforcement (i.e., the Wisconsin Card Sorting Test (WCST)). In laboratory animals, particularly non-human primates, variants of the WCST involve extensive training and testing on a series of dimensional discriminations, usually in social isolation. In the present study, a novel experimental approach was used to assess attentional set-shifting simultaneously in 12 rhesus monkeys. Specifically, monkeys living in individual cages but in the same room were trained at the same time each day in a set-shifting task in the same housing environment. As opposed to the previous studies, each daily session began with a simple single-dimension discrimination regardless of the animal’s performance on the previous session. A total of eight increasingly difficult, discriminations (sets) were possible in each daily 45 min session. Correct responses were reinforced under a second-order schedule of flavored food pellet delivery, and criteria for completing a set was 12 correct trials out of a running total of 15 trials. Monkeys progressed through the sets at their own pace and abilities. The results demonstrate that all 12 monkeys acquired the simple discrimination (the first set), but individual differences in the ability to progress through all eight sets were apparent. A performance index (PI) that encompassed progression through the sets, errors and session duration was calculated and used to rank each monkey’s performance in relation to each other. Overall, this version of a set-shifting task results in an efficient assessment of reliable differences in cognitive flexibility in a group of monkeys. PMID:28386222

  10. Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Galler R.

    2005-01-01

    Full Text Available A chimeric yellow fever (YF-dengue serotype 2 (dengue 2 virus was constructed by replacing the premembrane and envelope genes of the YF 17D virus with those from dengue 2 virus strains of Southeast Asian genotype. The virus grew to high titers in Vero cells and, after passage 2, was used for immunogenicity and attenuation studies in rhesus monkeys. Subcutaneous immunization of naive rhesus monkeys with the 17D-D2 chimeric virus induced a neutralizing antibody response associated with the protection of 6 of 7 monkeys against viremia by wild-type dengue 2 virus. Neutralizing antibody titers to dengue 2 were significantly lower in YF-immune animals than in YF-naive monkeys and protection against challenge with wild-type dengue 2 virus was observed in only 2 of 11 YF-immune monkeys. An anamnestic response to dengue 2, indicated by a sharp increase of neutralizing antibody titers, was observed in the majority of the monkeys after challenge with wild-type virus. Virus attenuation was demonstrated using the standard monkey neurovirulence test. The 17D-D2 chimera caused significantly fewer histological lesions than the YF 17DD virus. The attenuated phenotype could also be inferred from the limited viremias compared to the YF 17DD vaccine. Overall, these results provide further support for the use of chimeric viruses for the development of a new live tetravalent dengue vaccine.

  11. Sterile protection against Plasmodium knowlesi in rhesus monkeys from a malaria vaccine: comparison of heterologous prime boost strategies.

    Science.gov (United States)

    Jiang, George; Shi, Meng; Conteh, Solomon; Richie, Nancy; Banania, Glenna; Geneshan, Harini; Valencia, Anais; Singh, Priti; Aguiar, Joao; Limbach, Keith; Kamrud, Kurt I; Rayner, Jonathan; Smith, Jonathan; Bruder, Joseph T; King, C Richter; Tsuboi, Takafumi; Takeo, Satoru; Endo, Yaeta; Doolan, Denise L; Richie, Thomas L; Weiss, Walter R

    2009-08-10

    Using newer vaccine platforms which have been effective against malaria in rodent models, we tested five immunization regimens against Plasmodium knowlesi in rhesus monkeys. All vaccines included the same four P. knowlesi antigens: the pre-erythrocytic antigens CSP, SSP2, and erythrocytic antigens AMA1, MSP1. We used four vaccine platforms for prime or boost vaccinations: plasmids (DNA), alphavirus replicons (VRP), attenuated adenovirus serotype 5 (Ad), or attenuated poxvirus (Pox). These four platforms combined to produce five different prime/boost vaccine regimens: Pox alone, VRP/Pox, VRP/Ad, Ad/Pox, and DNA/Pox. Five rhesus monkeys were immunized with each regimen, and five Control monkeys received a mock vaccination. The time to complete vaccinations was 420 days. All monkeys were challenged twice with 100 P. knowlesi sporozoites given IV. The first challenge was given 12 days after the last vaccination, and the monkeys receiving the DNA/Pox vaccine were the best protected, with 3/5 monkeys sterilely protected and 1/5 monkeys that self-cured its parasitemia. There was no protection in monkeys that received Pox malaria vaccine alone without previous priming. The second sporozoite challenge was given 4 months after the first. All 4 monkeys that were protected in the first challenge developed malaria in the second challenge. DNA, VRP and Ad5 vaccines all primed monkeys for strong immune responses after the Pox boost. We discuss the high level but short duration of protection in this experiment and the possible benefits of the long interval between prime and boost.

  12. Sterile protection against Plasmodium knowlesi in rhesus monkeys from a malaria vaccine: comparison of heterologous prime boost strategies.

    Directory of Open Access Journals (Sweden)

    George Jiang

    Full Text Available Using newer vaccine platforms which have been effective against malaria in rodent models, we tested five immunization regimens against Plasmodium knowlesi in rhesus monkeys. All vaccines included the same four P. knowlesi antigens: the pre-erythrocytic antigens CSP, SSP2, and erythrocytic antigens AMA1, MSP1. We used four vaccine platforms for prime or boost vaccinations: plasmids (DNA, alphavirus replicons (VRP, attenuated adenovirus serotype 5 (Ad, or attenuated poxvirus (Pox. These four platforms combined to produce five different prime/boost vaccine regimens: Pox alone, VRP/Pox, VRP/Ad, Ad/Pox, and DNA/Pox. Five rhesus monkeys were immunized with each regimen, and five Control monkeys received a mock vaccination. The time to complete vaccinations was 420 days. All monkeys were challenged twice with 100 P. knowlesi sporozoites given IV. The first challenge was given 12 days after the last vaccination, and the monkeys receiving the DNA/Pox vaccine were the best protected, with 3/5 monkeys sterilely protected and 1/5 monkeys that self-cured its parasitemia. There was no protection in monkeys that received Pox malaria vaccine alone without previous priming. The second sporozoite challenge was given 4 months after the first. All 4 monkeys that were protected in the first challenge developed malaria in the second challenge. DNA, VRP and Ad5 vaccines all primed monkeys for strong immune responses after the Pox boost. We discuss the high level but short duration of protection in this experiment and the possible benefits of the long interval between prime and boost.

  13. Effects of vestibular prosthesis electrode implantation and stimulation on hearing in rhesus monkeys.

    Science.gov (United States)

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

    2011-07-01

    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 surgically manipulated. Hearing tests were conducted before implantation (BI) and then 4 weeks post-implantation both without electrical stimulation (NS) and with electrical stimulation (S). During the latter condition, prosthetic electrical stimuli encoding 3 dimensions of head angular velocity were delivered to the 3 ampullary branches of the left vestibular nerve via each of 3 electrode pairs of a multichannel vestibular prosthesis. Electrical stimuli comprised charge-balanced biphasic pulses at a baseline rate of 94 pulses/s, with pulse frequency modulated from 48 to 222 pulses/s by head angular velocity. ABR hearing thresholds to clicks and tone pips at 1, 2, and 4 kHz increased by 5-10 dB from BI to NS and increased another ∼5 dB from NS to S in implanted ears. No significant change was seen in right ears. DPOAE amplitudes decreased by 2-14 dB from BI to NS in implanted ears. There was a slight but insignificant decrease of DPOAE amplitude and a corresponding increase of DPOAE/Noise floor ratio between NS and S in implanted ears. Vestibular prosthesis electrode implantation and activation have small but measurable effects on hearing in rhesus monkeys. Coupled with the clinical observation that patients with cochlear implants only rarely exhibit signs of vestibular injury or spurious vestibular nerve stimulation, these results suggest that although implantation and activation of multichannel vestibular prosthesis electrodes in human will carry a risk of hearing loss

  14. 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

  15. What interests them in the pictures?--differences in eye-tracking between rhesus monkeys and humans.

    Science.gov (United States)

    Hu, Ying-Zhou; Jiang, Hui-Hui; Liu, Ci-Rong; Wang, Jian-Hong; Yu, Cheng-Yang; Carlson, Synnöve; Yang, Shang-Chuan; Saarinen, Veli-Matti; Rizak, Joshua D; Tian, Xiao-Guang; Tan, Hen; Chen, Zhu-Yue; Ma, Yuan-Ye; Hu, Xin-Tian

    2013-10-01

    Studies estimating eye movements have demonstrated that non-human primates have fixation patterns similar to humans at the first sight of a picture. In the current study, three sets of pictures containing monkeys, humans or both were presented to rhesus monkeys and humans. The eye movements on these pictures by the two species were recorded using a Tobii eye-tracking system. We found that monkeys paid more attention to the head and body in pictures containing monkeys, whereas both monkeys and humans paid more attention to the head in pictures containing humans. The humans always concentrated on the eyes and head in all the pictures, indicating the social role of facial cues in society. Although humans paid more attention to the hands than monkeys, both monkeys and humans were interested in the hands and what was being done with them in the pictures. This may suggest the importance and necessity of hands for survival. Finally, monkeys scored lower in eye-tracking when fixating on the pictures, as if they were less interested in looking at the screen than humans. The locations of fixation in monkeys may provide insight into the role of eye movements in an evolutionary context.

  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. Associations between early life experience, chronic HPA axis activity, and adult social rank in rhesus monkeys.

    Science.gov (United States)

    Dettmer, Amanda M; Wooddell, Lauren J; Rosenberg, Kendra L; Kaburu, Stefano S K; Novak, Melinda A; Meyer, Jerrold S; Suomi, Stephen J

    2017-02-01

    Early life experience and socioeconomic status (SES) are well-established predictors of health outcomes in people. Both factors likely influence health outcomes via hypothalamic-pituitary-adrenal (HPA) axis regulation. However, it is unclear how early experience and HPA axis activity influence adult social status. We studied differentially reared female rhesus monkeys (Macaca mulatta, N = 90) as models to test the hypothesis that chronic HPA axis activity assessed via hair cortisol concentrations (HCCs) mediated the relationship between early life experience and adult social rank. We found that mother-peer-reared (MPR) monkeys acquired higher social ranks than either of the two nursery-reared (NR) groups (peer-reared, PR, or surrogate-peer-reared, SPR monkeys) (β = -0.07, t(89) = -2.16, p = 0.034). We also found that MPR HCCs were lower during the juvenile period at 18 months (F(2,25) = 3.49, p = 0.047). Furthermore, for MPR but not NR monkeys, changes in HCCs from 18 to 24 months (r(s) = -0.627, p = 0.039) and adult HCCs (r(s) = -0.321, p = 0.03) were negatively correlated with adult social rank. These findings suggest that chronic HPA axis regulation in juvenility, and perhaps in adulthood, may influence adult social status for primates that experience typical early rearing. However, early life adversity may result in dissociation between neuroendocrine stress regulation and adult social competence, which may be risk factors for adverse health outcomes.

  18. 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.

  19. Wild dengue virus types 1, 2 and 3 viremia in rhesus monkeys.

    Science.gov (United States)

    Freire, M S; Marchevsky, R S; Almeida, L F C; Yamamura, A M Y; Caride, E C; Brindeiro, P A; Motta, M C A; Nogueira, R M R; Kubelka, C F; Bonaldo, M C; Galler, R

    2007-05-01

    Among the flaviviruses, dengue, with its four serotypes, has spread throughout the tropics. The most advanced vaccines developed so far include live attenuated viruses, which have been tested in humans but none has been licensed. Preclinical testing of dengue vaccine candidates is performed initially in mice and in nonhuman primates. In the latter the main criteria used to assay protection are neutralizing antibodies elicited by the vaccine candidate and the magnitude and duration of peripheral viremia upon challenge of previously immunized animals. Towards the identification of wild-type viruses that could be used in challenge experiments a total of 31 rhesus monkeys were inoculated subcutaneously of wild dengue types 1, 2, and 3 viruses. The viremia caused by the different viruses was variable but it was possible to identify dengue viruses useful as challenge strains.

  20. Wild dengue virus types 1, 2 and 3 viremia in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    MS Freire

    2007-03-01

    Full Text Available Among the flaviviruses, dengue, with its four serotypes, has spread throughout the tropics. The most advanced vaccines developed so far include live attenuated viruses, which have been tested in humans but none has been licensed. Preclinical testing of dengue vaccine candidates is performed initially in mice and in nonhuman primates. In the latter the main criteria used to assay protection are neutralizing antibodies elicited by the vaccine candidate and the magnitude and duration of peripheral viremia upon challenge of previously immunized animals. Towards the identification of wild-type viruses that could be used in challenge experiments a total of 31 rhesus monkeys were inoculated subcutaneously of wild dengue types 1, 2, and 3 viruses. The viremia caused by the different viruses was variable but it was possible to identify dengue viruses useful as challenge strains.

  1. Cortisol in Neonatal Mother's Milk Predicts Later Infant Social and Cognitive Functioning in Rhesus Monkeys.

    Science.gov (United States)

    Dettmer, Amanda M; Murphy, Ashley M; Guitarra, Denisse; Slonecker, Emily; Suomi, Stephen J; Rosenberg, Kendra L; Novak, Melinda A; Meyer, Jerrold S; Hinde, Katie

    2017-03-29

    Milk provides not only the building blocks for somatic development but also the hormonal signals that contribute to the biopsychological organization of the infant. Among mammals, glucocorticoids (GCs) in mother's milk have been associated with infant temperament. This study extended prior work to investigate rhesus monkey (Macaca mulatta) mother-infant dyads (N = 34) from birth through 8 months postpartum. Regression analysis revealed that cortisol concentrations in milk during the neonatal period predicted impulsivity on a cognitive task, but not global social behaviors, months later. During this time period, sex-differentiated social behavior emerged. For female infants, milk cortisol concentrations predicted total frequency of play. Collectively, these findings support and extend the "lactational programming" hypothesis on the impact of maternal-origin hormones ingested via milk. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  2. [Cellular composition of the lymph nodes of monkeys (rhesus macaque) under normal and experimental conditions].

    Science.gov (United States)

    Rusina, A K

    1978-01-01

    By means of mathematical methods, quantitative and qualitative changes were studied in different structural components of the mesenteric (ileocecal) lymph nodes in normal monkeys (Macaca rhesus) and under per os administration of Salmonella typhi murium, streptomycin-dependent. Cellular composition was calculated in the cortical plateau, cortical (lymphoid) cords and in follicules. Average percent of every cell type was determined. Vaccine administration, was stated to inhibit cytopoiesis in the cortical plateau and in the follicules with light centers. An inverse correlation was noted between the content of small and medium size lymphocytes. Different reactivity of certain structural components in the lymph nodes was demonstrated. As a response to the vaccine administration, plasmocellular acidophilic and macrophagal reactions were most pronounced in the cortical (lymphoid) cords.

  3. Sensory Processing in Rhesus Monkeys: Developmental Continuity, Prenatal Treatment, and Genetic Influences.

    Science.gov (United States)

    Schneider, Mary L; Moore, Colleen F; Adkins, Miriam; Barr, Christina S; Larson, Julie A; Resch, Leslie M; Roberts, Andrew

    2017-01-01

    Neonatal sensory processing (tactile and vestibular function) was tested in 78 rhesus macaques from two experiments. At ages 4-5 years, striatal dopamine D2 receptor binding was examined using positron emission tomography. At ages 5-7 years, adult sensory processing was assessed. Findings were: (a) prenatal stress exposure yielded less optimal neonatal sensory processing; (b) animals carrying the short rh5-HTTLPR allele had less optimal neonatal sensory scores than monkeys homozygous for the long allele; (c) neonatal sensory processing was significantly related to striatal D2 receptor binding for carriers of the short allele, but not for animals homozygous for the long allele; and (d) there was moderate developmental continuity in sensory processing from the neonatal period to adulthood.

  4. 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.

  5. 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

  6. Chronic oxytocin administration inhibits food intake, increases energy expenditure, and produces weight loss in fructose-fed obese rhesus monkeys.

    Science.gov (United States)

    Blevins, James E; Graham, James L; Morton, Gregory J; Bales, Karen L; Schwartz, Michael W; Baskin, Denis G; Havel, Peter J

    2015-03-01

    Despite compelling evidence that oxytocin (OT) is effective in reducing body weight (BW) in diet-induced obese (DIO) rodents, studies of the effects of OT in humans and rhesus monkeys have primarily focused on noningestive behaviors. The goal of this study was to translate findings in DIO rodents to a preclinical translational model of DIO. We tested the hypothesis that increased OT signaling would reduce BW in DIO rhesus monkeys by inhibiting food intake and increasing energy expenditure (EE). Male DIO rhesus monkeys from the California National Primate Research Center were adapted to a 12-h fast and maintained on chow and a daily 15% fructose-sweetened beverage. Monkeys received 2× daily subcutaneous vehicle injections over 1 wk. We subsequently identified doses of OT (0.2 and 0.4 mg/kg) that reduced food intake and BW in the absence of nausea or diarrhea. Chronic administration of OT for 4 wk (0.2 mg/kg for 2 wk; 0.4 mg/kg for 2 wk) reduced BW relative to vehicle by 3.3 ± 0.4% (≈0.6 kg; P intake by 26 ± 7% (P intake by 27 ± 5% (P intake by 18 ± 8% (P food intake as well as increased EE and lipolysis.

  7. Neuron Numbers in the Hypothalamus of the Normal Aging Rhesus Monkey: Stability Across the Adult Lifespan and Between the Sexes

    Science.gov (United States)

    Roberts, D.E.; Killiany, R.J.; Rosene, D.L.

    2014-01-01

    Normal aging is accompanied by changes in hypothalamic functions including autonomic and endocrine functions and circadian rhythms. The rhesus monkey provides an excellent model of normal aging without the potential confounds of incipient Alzheimer's disease inherent in human populations. This study examined the hypothalamus of 51 rhesus monkeys (23 male, 18 female, 6.5–31 years old) using design-based stereology to obtain unbiased estimates of neuron and glia numbers and the Cavalieri method to estimate volumes for eight reference spaces: total unilateral hypothalamus, suprachiasmatic nucleus (SCN), supraoptic nucleus (SON), paraventricular nucleus (PVN), dorsomedial nucleus (DM), ventromedial nucleus (VM), medial mammillary nucleus (MMN), and lateral hypothalamic area (LHA). The results demonstrated no age-related difference in neuron number, glia number, or volume in any area in either sex except the PVN of male monkeys, which showed a significant increase in both neuron and glia numbers with age. Comparison of males and females for sexual dimorphisms revealed no significant differences in neuron number. However, males had more glia overall as well as in the SCN, DM, and LHA and had a larger hypothalamic volume overall and in the SCN, SON, VM, DM, and MMN. These results demonstrate that hypothalamic neuron loss cannot account for age-related deficits in hypothalamic function and provides further evidence of the absence of neurode-generation and cell death in the normal aging rhesus monkey. PMID:21935936

  8. Effects of 12 days exposure to simulated microgravity on central circulatory hemodynamics in the rhesus monkey

    Science.gov (United States)

    Convertino, V. A.; Koenig, S. C.; Krotov, V. P.; Fanton, J. W.; Korolkov, V. I.; Trambovetsky, E. V.; Ewert, D. L.; Truzhennikov, A.; Latham, R. D.

    1998-01-01

    Central circulatory hemodynamic responses were measured before and during the initial 9 days of a 12-day 10 degrees head-down tilt (HDT) in 4 flight-sized juvenile rhesus monkeys who were surgically instrumented with a variety of intrathoracic catheters and blood flow sensors to assess the effects of simulated microgravity on central circulatory hemodynamics. Each subject underwent measurements of aortic and left ventricular pressures, and aortic flow before and during HDT as well as during a passive head-up postural test before and after HDT. Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure were measured, and dP/dt and left ventricular elastance was calculated from hemodynamic measurements. The postural test consisted of 5 min of supine baseline control followed by 5 minutes of 90 degrees upright tilt (HUT). Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure showed no consistent alterations during HDT. Left ventricular elastance was reduced in all animals throughout HDT, indicating that cardiac compliance was increased. HDT did not consistently alter left ventricular +dP/dt, indicating no change in cardiac contractility. Heart rate during the post-HDT HUT postural test was elevated compared to pre-HDT while post-HDT cardiac output was decreased by 52% as a result of a 54% reduction in stroke volume throughout HUT. Results from this study using an instrumented rhesus monkey suggest that exposure to microgravity may increase ventricular compliance without alternating cardiac contractility. Our project supported the notion that an invasively-instrumented animal model should be viable for use in spaceflight cardiovascular experiments to assess potential changes in myocardial function and cardiac compliance.

  9. 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.

  10. Rhesus monkey embryos produced by nuclear transfer from embryonic blastomeres or somatic cells.

    Science.gov (United States)

    Mitalipov, Shoukhrat M; Yeoman, Richard R; Nusser, Kevin D; Wolf, Don P

    2002-05-01

    Production of genetically identical nonhuman primates would reduce the number of animals required for biomedical research and dramatically impact studies pertaining to immune system function, such as development of the human-immunodeficiency-virus vaccine. Our long-term goal is to develop robust somatic cell cloning and/or twinning protocols in the rhesus macaque. The objective of this study was to determine the developmental competence of nuclear transfer (NT) embryos derived from embryonic blastomeres (embryonic cell NT) or fetal fibroblasts (somatic cell NT) as a first step in the production of rhesus monkeys by somatic cell cloning. Development of cleaved embryos up to the 8-cell stage was similar among embryonic and somatic cell NT embryos and comparable to controls created by intracytoplasmic sperm injection (ICSI; mean +/- SEM, 81 +/- 5%, 88 +/- 7%, and 87 +/- 4%, respectively). However, significantly lower rates of development to the blastocyst stage were observed with somatic cell NT embryos (1%) in contrast to embryonic cell NT (34 +/- 15%) or ICSI control embryos (46 +/- 6%). Development of somatic cell NT embryos was not markedly affected by donor cell treatment, timing of activation, or chemical activation protocol. Transfer of embryonic, but not of somatic cell NT embryos, into recipients resulted in term pregnancy. Future efforts will focus on optimizing the production of somatic cell NT embryos that develop in high efficiency to the blastocyst stage in vitro.

  11. Induced neurocysticercosis in rhesus monkeys (Macaca mulatta) produces clinical signs and lesions similar to natural disease in man.

    Science.gov (United States)

    Chowdhury, N; Saleque, A; Sood, N K; Singla, L D

    2014-01-01

    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.

  12. 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.

  13. Ethograms indicate stable well-being during prolonged training phases in rhesus monkeys used in neurophysiological research.

    Science.gov (United States)

    Hage, Steffen R; Ott, Torben; Eiselt, Anne-Kathrin; Jacob, Simon N; Nieder, Andreas

    2014-01-01

    Awake, behaving rhesus monkeys are widely used in neurophysiological research. Neural signals are typically measured from monkeys trained with operant conditioning techniques to perform a variety of behavioral tasks in exchange for rewards. Over the past years, monkeys' psychological well-being during experimentation has become an increasingly important concern. We suggest objective criteria to explore whether training sessions during which the monkeys work under controlled water intake over many days might affect their behavior. With that aim, we analyzed a broad range of species-specific behaviors over several months ('ethogram') and used these ethograms as a proxy for the monkeys' well-being. Our results show that monkeys' behavior during training sessions is unaffected by the duration of training-free days in-between. Independently of the number of training-free days (two or nine days) with ad libitum food and water supply, the monkeys were equally active and alert in their home group cages during training phases. This indicates that the monkeys were well habituated to prolonged working schedules and that their well-being was stably ensured during the training sessions.

  14. Ordered recall in rhesus macaques (Macaca mulatta: Can monkeys recall the correct order of sequentially presented images?

    Directory of Open Access Journals (Sweden)

    Heather E O'Neil

    2006-01-01

    Full Text Available Previous research has demonstrated that rhesus monkeys (Macaca mulatta are capable of identifying sequentially shown images in any order among distractors (i.e. images not part of the list sequence. We investigated ordered recall in rhesus monkeys in which subjects were expected to recognize the correct order of images during a “test” phase (simultaneous presentation of images after they had seen the images presented sequentially in a “presentation” phase (sequential presentation of images. If subjects were successfully able to execute the ordered recall task, the first trial accuracy data would appear close to 100% accuracy and it would only take one day to learn the list since the lists used were short, 3-item lists. While this study did not conclusively demonstrate monkeys are capable of ordered recall of sequentially presented, trial unique images (i.e. a list sequence presented only once per session, the data suggests that when the stimuli are not trial unique the monkeys treat each sequence as a simultaneous chaining task. A simultaneous chaining paradigm entails simultaneous presentation of all items without any previous sequential presentation of the images. It is unclear whether results resembling simultaneous chaining are seen because these animals have previous experience with simultaneous chaining, if the training procedure needs to be modified for the monkeys to understand the task, or if the task is beyond their cognitive abilities. Further research with serial learning will clarify this finding and also seek to prove whether rhesus monkeys are in fact capable of such ordered recall tasks.

  15. Radioimmunoassay of arginine vasopressin in Rhesus Monkey plasma. [/sup 125/I tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Hayward, J.N.; Pavasuthipaisit, K.; Perez-Lopez, F.R.; Sofroniew, M.V.

    1976-04-01

    Using a new antiserum and an enzymatic radioiodination of arginine vasopressin (AVP), we have developed a sensitive and specific radioimmunoassay for plasma AVP in the monkey. The sensitivity of the assay is 0.5 ..mu..U/ml, the cross reaction with oxytocin (OT), minimal. We used this assay to study the effects that variations in blood osmolality have in regulating AVP secretion in unanesthetized, chair-restrained, chamber-isolated, adult female rhesus monkeys. Under water ad lib conditions, plasma AVP and osmolality were relatively constant, averaging 1.7 +- 0.6 (SD) ..mu..U/ml and 298 +- 3 mosmol/kg, respectively. Water loading decreased plasma AVP and osmolality to 0.6 +- 0.2 ..mu..U/ml and 282 +- 6 mosmol/kg, respectively. When fluid restriction increased osmolality, plasma AVP rose progressively to twice the baseline after 1 day, and to 6 times the baseline after 3 days. The rise in plasma AVP was linearly correlated with the rise in osmolality (r = 0.93; P less than 0.001). Intravenous infusions of hypertonic saline produced significant rises in plasma osmolality and plasma AVP. There was a dose-related rise in plasma AVP that declined later at the expected rate with the infusion of physiological amounts of synthetic AVP.

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

    Directory of Open Access Journals (Sweden)

    Hengxi Wei

    2015-01-01

    Full Text Available 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.

  17. Aspartame demand in rhesus monkeys: effects of volume and concentration manipulations.

    Science.gov (United States)

    Wade-Galuska, Tammy; Galuska, Chad M; Winger, Gail; Woods, James H

    2007-01-10

    Three rhesus monkeys' lever presses produced aspartame-sweetened water according to a fixed-ratio schedule. The response requirement was increased across sessions and a demand-function analysis was used to assess the reinforcing effectiveness of different magnitudes of aspartame by manipulating reinforcer duration (1 and 3s) in Phase 1 and concentration (0.3, 0.5, 0.7, and 1.0mg/ml) in Phase 2. When duration was manipulated, the number of aspartame deliveries was mainly a function of the response requirement rather than unit price (responses/duration), suggesting that changes in duration did not significantly affect the reinforcing effectiveness of aspartame. When concentration was manipulated and the lowest concentration excluded, consumption was best described by unit price (responses/concentration) in two monkeys and by the response requirement in the third. Although results from the concentration manipulation provide some evidence that consumption was modulated by unit price, the results overall suggest that scalar equivalence does not exist between the components of unit price; specifically, the response requirement exerted a larger influence than duration or concentration on total consumption. Finally, a normalized demand analysis revealed that aspartame is a more elastic commodity than food and drug reinforcers.

  18. 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.

  19. The effects of succimer chelation therapy on auditory function in rhesus monkeys.

    Science.gov (United States)

    Lasky, R E; Luck, M L; Laughlin, N K

    2001-01-01

    Sixty-six female rhesus monkeys were randomly assigned to three lead exposure conditions (none, from birth to 1 year, and from birth to 2 years) by two chelation treatment (succimer and no succimer) conditions. Blood lead levels were maintained at 35-40 microg/dl beginning shortly after birth and continuing for 1 or 2 years postnatally. There were two separate chelation regimes: 53 and 65 weeks of age. Lead and lead-vehicle dosing were discontinued while succimer was administered. Succimer (or placebo) was administered orally at a dose of 30 mg/kg/day (divided into three doses per day) for 5 days and for 14 additional days at 20 mg/kg/day (divided into two doses per day) for a total 19-day treatment regimen. Auditory function was assessed in these monkeys at least 1 year after lead intake had been discontinued. The outcome measures included tympanometry to assess middle ear function, OAEs to assess cochlear function, and ABRs to assess the auditory nerve and brainstem pathways. There were no significant differences as a function of succimer treatment for any of the tympanometric variables measured. Suprathreshold and threshold distortion product otoacoustic emissions were comparable among the succimer and vehicle groups. However, there was a nonsignificant trend to smaller amplitude distortion products at the highest frequencies assessed (6.4-10.0 kHz). Finally, the auditory evoked response at levels from the auditory nerve to the cerebral cortex did not significantly differ as a function of succimer treatment.

  20. 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.

  1. 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 < 0.001) than that produced by PHA (MI < 0.01) in lymphocytes from the same 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.

  2. Age-related changes in fasting plasma cortisol in rhesus monkeys: implications of individual differences for pathological consequences.

    Science.gov (United States)

    Erwin, Joseph M; Tigno, Xenia T; Gerzanich, Georgielle; Hansen, Barbara C

    2004-05-01

    Elevated cortisol may damage receptor neurons involved in responses to stress, leading to progressive metabolic dysregulation and age-related increases in cortisol; however, documentation of rising cortisol with age in humans has been inconsistent. Here we report fasting cortisol values from rhesus monkeys maintained for obesity, diabetes, and aging research. A modest correlation (r =.20) between age and cortisol was found for 138 rhesus monkeys (aged 4-40 years) and (r =.16) for 30 males for whom at least 10 years of longitudinal data were available. Subgroups of ad libitum-fed and weight-stabilized animals also exhibited significant positive relationships between age and cortisol (r =.14-.37). Individual regression analyses revealed both significant increases (r =.29-.85) and decreases (r = -.47 to -.66) in cortisol relative to age. Unexpectedly, significant age-related increases occurred in 77% of healthy primates, but only 33% of diabetic primates, while significant declines occurred only in diabetics.

  3. The behavioral neurobiology of self-injurious behavior in rhesus monkeys.

    Science.gov (United States)

    Kraemer, G W; Clarke, A S

    1990-01-01

    1. Self-injurious behavior (SIB) is prevalent among institutionalized children, but the efficacy of current behavioral and pharmacological treatments is marginal. 2. There is evidence that SIB in humans has a neurobiological basis. A better understanding of the neurobiological factors that may promote or cause SIB is necessary for the development of effective pharmacologic treatments. 3. SIB that is similar in some respects to SIB in humans occurs in nonhuman primates that have been deprived of social experience early in life. An analysis of the "cause" of SIB suggests that it is a relatively straight-forward example of the development of neurobiological and behavioral aspects of aggressive behavior in the absence of social factors that would normally bring the behavior under environmental control. Once induced, however, it becomes environmentally autonomous and its proximal cause is neurobiological in nature. 4. There are three lines of evidence that nonhuman primate SIB is linked to malfunctions in the norepinephrine (NE) and serotonin (5HT) neurotransmitter systems. The activity of these systems appears to be altered by psychosocial deprivation. The functional relationship between the two systems appears to be altered or absent in socially deprived monkeys. Pharmacologic agents that act on these systems alter SIB in monkeys. 5. Preliminary data from socially deprived rhesus monkeys are consistent in major respects with studies linking altered serotonin systems to self-injurious behavior and suicidal motivation in humans who also probably suffer from social deprivation. 6. Taken together, these findings indicate that developmental study of biogenic amine systems, particularly finding ways to circumvent deficits in, or restore functional linkages between, the 5HT and NE systems, will lead to a greater understanding of the neurobiologic basis of SIB in humans and animals and will enable us to develop more effective treatments of SIB.

  4. Discriminative stimulus effects of benzodiazepine (BZ)(1) receptor-selective ligands in rhesus monkeys.

    Science.gov (United States)

    McMahon, Lance R; Gerak, Lisa R; Carter, Lawrence; Ma, Chunrong; Cook, James M; France, Charles P

    2002-02-01

    Drug discrimination was used to examine the effects of benzodiazepine (BZ)(1) receptor-selective ligands in rhesus monkeys. In diazepam-treated (5.6 mg/kg, p.o.) monkeys discriminating the nonselective BZ antagonist flumazenil (0.32 mg/kg, s.c.), the BZ(1)-selective antagonist beta-carboline-3-carboxylate-t-butyl ester (beta-CCt) substituted for flumazenil. The onset of action of beta-CCt was delayed with a dose of 5.6 mg/kg beta-CCt substituting for flumazenil 2 h after injection. In monkeys discriminating the nonselective BZ agonist midazolam (0.56 mg/kg, s.c.), the BZ(1)-selective agonists zaleplon (ED(50) = 0.78 mg/kg) and zolpidem (ED(50) = 1.73 mg/kg) substituted for midazolam. The discriminative stimulus effects of midazolam, zaleplon, and zolpidem were antagonized by beta-CCt (1.0-5.6 mg/kg, s.c.), and the effects of zaleplon and zolpidem were also antagonized by flumazenil (0.01-0.32 mg/kg, s.c.). Schild analyses supported the notion of a simple, competitive interaction between beta-CCt and midazolam (slope = -1.08; apparent pA(2) = 5.41) or zaleplon (slope = -1.57; apparent pA(2) = 5.49) and not between beta-CCt and zolpidem. Schild analyses also were consistent with a simple, competitive interaction between flumazenil and zaleplon (slope = -1.03; apparent pA(2) = 7.45) or zolpidem (slope = -1.11; apparent pA(2) = 7.63). These results suggest that the same BZ receptor subtype(s) mediate(s) the effects of midazolam, zolpidem, and zaleplon under these conditions and that selective binding of BZ ligands does not necessarily confer selective effects in vivo.

  5. Influence of Amplitude, Starting Point, and Age on First- and Second-Order Dynamics of Edinger-Westphal–Stimulated Accommodation in Rhesus Monkeys

    OpenAIRE

    Baumeister, Martin; Wendt, Mark; Glasser, Adrian

    2010-01-01

    First- and second-order dynamics of Edinger-Westphal–stimulated accommodation in rhesus monkeys depend on the amplitude but not on the starting point of the response. The disaccommodative peak velocity for a given amplitude is lower in older than in younger monkeys.

  6. Potent SIV-specific Cellular Immune Responses in the Breast Milk of SIV-infected, Lactating Rhesus Monkeys1

    OpenAIRE

    2008-01-01

    Breast milk transmission of HIV is a leading cause of infant HIV/AIDS in the developing world. Remarkably, only a small minority of breastfeeding infants born to HIV-infected mothers contract HIV via breast milk exposure, raising the possibility that immune factors in the breast milk confer protection to the infants who remain uninfected. To model HIV-specific immunity in breast milk, lactation was pharmacologically induced in Mamu-A*01+ female rhesus monkeys. The composition of lymphocyte su...

  7. Type 2 diabetes mellitus non-genetic Rhesus monkey model induced by high fat and high sucrose diet.

    Science.gov (United States)

    Lu, Shuai-yao; Qi, Su-dong; Zhao, Yuan; Li, Yan-yan; Yang, Feng-mei; Yu, Wen-hai; Jin, Ma; Chen, Li-Xiong; Wang, Jun-bin; He, Zhan-long; Li, Hong-jun

    2015-01-01

    To build an ideal animal model for studying the mechanism of occurrence, developing and treating of diabetes become a more important issue, facing with the fact that the big threat of diabetes to human health has been worsen. First, we used the normal control diets or the high-fat/high-sucrose diets to feed the adult rhesus monkeys and the macaques induced by the high-fat/high-sucrose diets in the high-fat/high-sucrose group and the type 2 diabetes mellitus (T2DM) group developed the hyperglycemia, hyperinsulinemia at 6 months in accordance with the precious researches that reported that minipigs, rats and mice could develop hyperglycemia, hyperinsulinemia, hyperlipidemia and obesity after being induced with high-fat/high-carbohydrate diets. Second, the rhesus monkeys in T2DM group were injected STZ at a low dosage of 35 mg/kg BW to induce glucose persistent elevation which maintained pretty well after 12 months. Third, we took the assay of glucose tolerance test and insulin resistance index, assessed the changing tendency of serum resistin and analysed the pathological characteristics of the tissues like pancreas and liver by staining in different ways. The results indicate the rhesus monkeys in T2DM group have lots of clinical features of T2DM. The experimental non-genetic T2DM rhesus monkeys model not only contribute to simulating of clinical manifestations and pathological features of human T2DM, but also may be a good kind of model for research on the treatment of T2DM and for new drugs evaluation.

  8. Recombinant poxvirus boosting of DNA-primed rhesus monkeys augments peak but not memory T lymphocyte responses

    OpenAIRE

    Santra, Sampa; Barouch, Dan H.; Korioth-Schmitz, Birgit; Lord, Carol I.; Krivulka, Georgia R.; Yu, Faye; Beddall, Margaret H; Gorgone, Darci A.; Lifton, Michelle A.; Miura, Ayako; Philippon, Valerie; Manson, Kelledy; Markham, Phillip D.; Parrish, John; Kuroda, Marcelo J.

    2004-01-01

    Although a consensus has emerged that an HIV vaccine should elicit a cytotoxic T lymphocyte (CTL) response, the characteristics of an effective vaccine-induced T lymphocyte response remain unclear. We explored this issue in the simian human immunodeficiency virus/rhesus monkey model in the course of assessing the relative immunogenicity of vaccine regimens that included a cytokine-augmented plasmid DNA prime and a boost with DNA or recombinant pox vectors. Recombinant vaccinia virus, recombin...

  9. Computational Fluid Dynamics Simulations of Inhaled Nano-and Micro-Particle Deposition in the Rhesus Monkey Nasal Passages

    Science.gov (United States)

    2016-12-01

    been used to assess effects from inhalation of reactive gases such as ozone, chlorine and formaldehyde ( Carey et al., 2007; Klonne et al., 1987...model according to the definitions from Carey et al. (2007) and Kimbell et al. (2001) (see Figure 2-1 and Table 2-1). The remaining surface is...Jacob, R. E., Harkema, J., Carey , S. A., Schelegle, E., Hyde, D., Kimbell, J. S., and Miller, F. J. (2012). Development of a rhesus monkey lung

  10. Effect of hypoxia by intermittent altitude exposure on semen characteristics and testicular morphology of male rhesus monkeys

    Science.gov (United States)

    Saxena, D. K.

    1995-09-01

    Semen characteristics and testicular morphology of rhesus monkeys were studied on exposure to a simulated high altitude of 4411 m for 21 days. There was a partially reversible decrease in the semen volume, sperm count and sperm motility, as well as an elevation of pH and fructose concentration. These changes were associated with degeneration of the germinal epithelium and spermatogenic arrest at the end of third week of exposure which had not recovered even 3 weeks after the exposure.

  11. Characterization of perfect microsatellite based on genome-wide and chromosome level in Rhesus monkey (Macaca mulatta).

    Science.gov (United States)

    Xu, Yongtao; Hu, Zongxiu; Wang, Chen; Zhang, Xiuyue; Li, Jing; Yue, Bisong

    2016-11-05

    Microsatellite studies based on chromosomes level would contribute to the biometric correlation analysis of chromosome and microsatellite applications on the specific chromosome. In this study, the total microsatellite length of 1,141,024 loci was 21.8Mb, which covered about 0.74% of the male Rhesus monkey genome. Perfect mononucleotide SSRs were the most abundant, followed by the pattern: perfect di->tetra->tri->penta->hexanucleotide SSRs. The main range of repeat times focused on 12-32 times (mono-), 7-23 times (di-), 5-10 times (tri-), 4-14 times (tetra-), 4-9 times (penta-), 4-8 times (hexa-), respectively. The largest SSRs number was found in chromosome 1 with 94,347 loci, followed by chromosome 3, 2, 7 and 5, and the smallest number was in chromosome 18. The predominant repeat types in male Rhesus monkey genome and chromosome Y were basically A, AC, AG, AAT, AAC, AAAT, AAAC, AAAG, AAACA and AAACAA. SSRs number of all chromosomes was closely positively correlated with chromosome sequence size (r=0.969, pmicrosatellite density (r=-0.456, 0.01microsatellites structural function, composition mode and molecular markers development in Rhesus monkey genome.

  12. 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

    2016-03-02

    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.

  13. Establishment of a rhesus monkey model of middle cerebral artery ischemia and reperfusion using a microcatheter embolization method

    Institute of Scientific and Technical Information of China (English)

    Jie Yang; Xiaoqi Huang; Hongxia Li; Li Wang; Jingqiu Cheng; Jian Guo; Hongbo Zheng; Muke Zhou; Li He; Wenying Cao; Li Xiao; Jiachuan Duan; Qiyong Gong

    2010-01-01

    Nonhuman primates are closest to humans in terms of lineage,and middle cerebral artery ischemia/reperfusion responses of nonhuman primates are most similar to ischemic stroke in humans.Therefore,nonhuman primates could be utilized to simulate the process of ischemic stroke in the human.Few studies,however,have reported the use of endovascular technology to establish a rhesus monkey stroke model.In the present study,seven adult,male,rhesus monkeys were selected and,following anesthesia,a microcatheter was inserted into one side of the middle cerebral artery via the femoral artery to block blood flow,thereby resulting in middle cerebral artery occlusion.After 2 hours,the microcatheter was withdrawn to restore the middle cerebral artery blood flow and to establish ischemia/reperfusion.Results from angiography and magnetic resonance angiography confirmed occlusion and reopening of the middle cerebral artery.Magnetic resonance imaging revealed the existence of ischemic brain lesions,and neurological examination showed sustained functional deficits following surgery.The rhesus monkey middle cerebral artery ischemia/reperfusion models established by microcatheter embolization had the advantage of non—craniotomy invasion and reproducibility.The scope and degree of ischemic damage using this model was controllable.Therefore,this nonhuman primate model is an ideal model for cerebral ischemia and reperfusion.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

  16. A 4-channel 3 Tesla phased array receive coil for awake rhesus monkey fMRI and diffusion MRI experiments.

    Science.gov (United States)

    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 challenges associated with constructing phased array coils for monkeys are the variation in head size and space constraints. Here, we apply phased array technology to a 4-channel phased array coil capable of improving the resolution and image quality of full brain awake monkey fMRI and diffusion MRI experiments. The phased array coil is that can adapt to different rhesus monkey head sizes (ages 4-8) and fits in the limited space provided by monkey stereotactic equipment and provides SNR gains in primary visual cortex and anatomical accuracy in conjunction with parallel imaging and improves resolution in fMRI experiments by a factor of 2 (1.25 mm to 1.0 mm isotropic) and diffusion MRI experiments by a factor of 4 (1.5 mm to 0.9 mm isotropic).

  17. Looking ahead? Computerized maze task performance by chimpanzees (Pan troglodytes), rhesus monkeys (Macaca mulatta), capuchin monkeys (Cebus apella), and human children (Homo sapiens).

    Science.gov (United States)

    Beran, Michael J; Parrish, Audrey E; Futch, Sara E; Evans, Theodore A; Perdue, Bonnie M

    2015-05-01

    Human and nonhuman primates are not mentally constrained to the present. They can remember the past and-at least to an extent-anticipate the future. Anticipation of the future ranges from long-term prospection such as planning for retirement to more short-term future-oriented cognition such as planning a route through a maze. Here we tested a great ape species (chimpanzees), an Old World monkey species (rhesus macaques), a New World monkey species (capuchin monkeys), and human children on a computerized maze task. All subjects had to move a cursor through a maze to reach a goal at the bottom of the screen. For best performance on the task, subjects had to "plan ahead" to the end of the maze to move the cursor in the correct direction, avoid traps, and reverse directions if necessary. Mazes varied in difficulty. Chimpanzees were better than both monkey species, and monkeys showed a particular deficit when moving away from the goal or changing directions was required. Children showed a similar pattern to monkeys regarding the effects of reversals and moves away from the goal, but their overall performance in terms of correct maze completion was similar to the chimpanzees. The results highlight similarities as well as differences in planning across species and the role that inhibitory control may play in future-oriented cognition in primates.

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

    Directory of Open Access Journals (Sweden)

    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

  19. 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.

  20. Pharmacokinetic profile of a new anticonvulsant, stiripentol, in the rhesus monkey.

    Science.gov (United States)

    Lin, H S; Levy, R H

    1983-12-01

    Stiripentol is a new anticonvulsant drug derived from phenyl-l-pentene-ol. One of its metabolites resulting from opening of the methylenedioxy ring also possesses anticonvulsant activity. This study undertook to define the overall pharmacokinetic profile of stiripentol in rhesus monkey prior to its efficacy evaluation. The experimental design included six treatments (three intravenous doses of 40, 80, and 120 mg; one oral dose of 80 mg; and two intraperitoneal doses of 80 and 120 mg) administered to five chaired rhesus monkeys in a randomized fashion. Sixteen plasma samples were obtained over 7 h and urine was collected for 24 h. A high-performance liquid chromatography assay was developed for the determination of stiripentol in plasma and urine (C8 reverse phase column and UV detection, lambda = 254 nm). The intravenous data revealed multiexponential behavior and therefore noncompartmental methods were used to describe the pharmacokinetics of stiripentol. Values for plasma clearances (L/h/kg) were 1.10 +/- 0.07 (40 mg), 0.92 +/- 0.08 (80 mg), and 0.86 +/- 0.15 (120 mg). The decrease in clearance with dose provided evidence of nonlinearity. The average mean residence time was 1.09 +/- 0.03 h. The average volume of distribution at steady state was 1.03 +/- 0.3 L/kg. The bioavailabilities obtained for the oral and intraperitoneal doses were consistent with first-pass effect predictions: 0.3 (oral), 0.32 (i.p. 80 mg), and 0.34 (i.p. 120 mg). The free fraction determined by equilibrium dialysis was less than 1%. The fraction of dose excreted unchanged in urine ranged between 0 and 3%. The metabolite with anticonvulsant activity could not be detected in plasma with any of the modes of administration. However, it was found in urine and accounted for 2% of the dose. The fraction metabolized by glucuronidation was 34.8 +/- 9.1%. The percentages of total amount of glucuronide excreted in the intervals 0-2, 2-4, 4-8, and 8-24 h were 70.6 +/- 6.2, 10.1 +/- 5.4, 13.6 +/- 5

  1. 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

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

    Directory of Open Access Journals (Sweden)

    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

  3. Metabolism of /sup 14/C-labeled doxylamine succinate (Bendectin) in the rhesus monkey (Macaca mulatta)

    Energy Technology Data Exchange (ETDEWEB)

    Slikker, W. Jr.; Holder, C.L.; Lipe, G.W.; Korfmacher, W.A.; Thompson, H.C. Jr.; Bailey, J.R.

    1986-05-01

    The time-course of the metabolic fate of (/sup 14/C)doxylamine was determined after the p.o. administration of 13 mg/kg doxylamine succinate as Bendectin plus (/sup 14/C)doxylamine succinate to the rhesus monkey. Urine and plasma samples were analyzed by reversed-phase high performance liquid chromatography (HPLC), chemical derivatization, and mass spectrometry. The cumulative 48-hr urinary metabolic profile contained 81% of the administered radiolabeled dose and consisted of at least six radiolabeled peaks. They were peak 1: unknown polar metabolites (8% of dose); peak 2: 2-(1-phenyl-1-(2-pyridinyl)ethoxy) acetic acid, 1-(1-phenyl-1(2-pyridinyl)ethoxy) methanol, and another minor metabolite(s) (31%); peak 3: doxylamine-N-oxide (1%); peak 4a: N,N-didesmethyldoxylamine (17%); peak 4b: doxylamine (4%); and peak 5: N-desmethyldoxylamine (20%). The plasma metabolic profile was the same as the urinary profile except for the absence of doxylamine-N-oxide. The maximum plasma concentrations and elapsed time to attain these concentrations were as follows. Peak 1: 540 ng/mL, 4 hr; peak 2: 1700 ng/mL, 1 hr; peak 4a: 430 ng/mL, 4 hr; peak 4b: 930 ng/mL, 2 hr; and peak 5: 790 ng/mL, 2 hr. These data suggest that in the monkey, doxylamine metabolism follows at least four pathways: a minor pathway to the N-oxide; a minor pathway to unknown polar metabolites; a major pathway to mono- and didesmethyldoxylamine via successive N-demethylation; and a major pathway to side-chain cleavage products (peak 2) via direct side-chain oxidation and/or deamination.

  4. Salmon calcitonin reduces food intake through changes in meal sizes in male rhesus monkeys.

    Science.gov (United States)

    Bello, Nicholas T; Kemm, Matthew H; Moran, Timothy H

    2008-07-01

    Amylinergic mechanisms are believed to be involved in the control of appetite. This study examined the effects of the amylin agonist, salmon calcitonin, on food intake and meal patterns in adult male rhesus monkeys. Fifteen minutes before the onset of their 6-h daily feeding period, monkeys received intramuscular injections of various doses of salmon calcitonin (0.032, 0.056, 0.1, 0.32, and 1 microg/kg) or saline. Salmon calcitonin dose dependently reduced total daily and hourly food intake, with significant decreases at the 0.1, 0.32, and 1 microg/kg doses. Daily food intake was reduced by approximately 35%, 62%, and 96%, at these doses, respectively. An analysis of meal patterns revealed that size of the first meal was significantly reduced across the dose range of 0.056 to 1 microg/kg, while average meal size was reduced with the 0.32 and 1 microg/kg doses. Meal number was only affected at the 1 microg/kg dose. Repeated 5-day administration of the 0.1 microg/kg dose resulted in a reduction in daily food intake only on injection day 2, while significant reductions in food intake were observed on all five injection days with a 0.32 microg/kg dose. Daily food intake was also reduced for 1 day after the termination of the 5-day injections of the 0.32 microg/kg salmon calcitonin dose. These sustained reductions in intake were expressed through decreases in meal size. These data demonstrate that salmon calcitonin acutely and consistently decreases food intake mainly through reductions in meal sizes in nonhuman primates.

  5. A behavioral taxonomy of loneliness in humans and rhesus monkeys (Macaca mulatta.

    Directory of Open Access Journals (Sweden)

    John P Capitanio

    Full Text Available Social relationships endow health and fitness benefits, but considerable variation exists in the extent to which individuals form and maintain salutary social relationships. The mental and physical health effects of social bonds are more strongly related to perceived isolation (loneliness than to objective social network characteristics. We sought to develop an animal model to facilitate the experimental analysis of the development of, and the behavioral and biological consequences of, loneliness. In Study 1, using a population-based sample of older adults, we examined how loneliness was influenced both by social network size and by the extent to which individuals believed that their daily social interactions reflected their own choice. Results revealed three distinct clusters of individuals: (i individuals with large networks who believed they had high choice were lowest in loneliness, (ii individuals with small social networks who believed they had low choice were highest in loneliness, and (iii the remaining two groups were intermediate and equivalent in loneliness. In Study 2, a similar three-group structure was identified in two separate samples of adult male rhesus monkeys (Macaca mulatta living in large social groups: (i those high in sociability who had complex social interaction with a broad range of social partners (putatively low in loneliness, (ii those low in sociability who showed tentative interactions with certain classes of social partners (putatively high in loneliness, and (iii those low in sociability who interacted overall at low levels with a broad range of social partners (putatively low or intermediate in loneliness. This taxonomy in monkeys was validated in subsequent experimental social probe studies. These results suggest that, in highly social nonhuman primate species, some animals may show a mismatch between social interest and social attainment that could serve as a useful animal model for experimental and

  6. 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.

  7. Transfer of hexachlorobenzene and polychlorinated biphenyls to nursing infant rhesus monkeys: enhanced toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, J.; Knauf, V.; Mueller, W.; Hobson, W.

    1980-02-01

    Clophen A-30 (CA-30 or PCB) or hexachlorobenzene (HCB) were given daily by gavage to lactating rhesus monkeys for either 30 days (CA-30, 16 mg/kg/day) or 60 days (HCB, 64 mg/kg/day) to three infant-mother pairs per compound. The extent to which the CA-30 or HCB were concentreated in the milk of the mothers and consequently transferred to the nursing infants was determined by measuring concentrations of both substances in milk and serum samples collected at frequent intervals. One mother and all the infants from each group were sacrificed and the tissue content of HCB or PCBs measured. Milk concentrations averaged 20 and 17 times higher than maternal serum levels for CA-300 and HCB-treated monkeys, respectively. Infant serum levels were approximately two to three (PCBs)-or two to five (HCB)-fold higher than serum concentrations in their mothers. All of the HCB-treated mothers remained healthy during dosing but one infant became moribund and was sacrificed on Day 22, and another died on Day 38. One CA-30-treated infant-mother pair was sacrificed on Day 23 of the study when they developed severe symptoms of poisoning. In general tissue levels of both HCB and Ca-30 were higher in the infants than in their mothers. Both HCB and PCB were concentrated in the infant fat, bone marrow, and adrenals. These findings are consistent with the hypothesis that nursing infants are at greater risk than their mothers when the mothers are exposed to lipophilic toxins.

  8. Neurotoxic lesions of the medial mediodorsal nucleus of the thalamus disrupt reinforcer devaluation effects in rhesus monkeys.

    Science.gov (United States)

    Mitchell, Anna S; Browning, Philip G F; Baxter, Mark G

    2007-10-17

    The mediodorsal thalamus is a major input to the prefrontal cortex and is thought to modulate cognitive functions of the prefrontal cortex. Damage to the medial, magnocellular part of the mediodorsal thalamus (MDmc) impairs cognitive functions dependent on prefrontal cortex, including memory. The contribution of MDmc to other aspects of cognition dependent on prefrontal cortex has not been determined. The ability of monkeys to adjust their choice behavior in response to changes in reinforcer value, a capacity impaired by lesions of orbital prefrontal cortex, can be tested in a reinforcer devaluation paradigm. In the present study, rhesus monkeys with bilateral neurotoxic MDmc lesions were tested in the devaluation procedure. Monkeys learned visual discrimination problems in which each rewarded object is reliably paired with one of two different food rewards and then were given choices between pairs of rewarded objects, one associated with each food. Selective satiation of one of the food rewards reduces choices of objects associated with that food in normal monkeys. Monkeys with bilateral neurotoxic lesions of MDmc learned concurrently presented visual discrimination problems as quickly as unoperated control monkeys but showed impaired reinforcer devaluation effects. This finding suggests that the neural circuitry for control of behavioral choice by changes in reinforcer value includes MDmc.

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

    Energy Technology Data Exchange (ETDEWEB)

    Slikker, W. Jr.; Althaus, Z.R.; Rowland, J.M.; Hill, D.E.; Hendrickx, A.G.

    1982-11-01

    The late gestational age rhesus monkey was used to study the transplacental pharmacokinetics of radiolabeled triamcinolone acetonide (TAC) and cortisol. Tritiated-TAC and (/sup 14/C)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 /sup 3/H in the fetal circulation was parent TAC, whereas only 14 to 49% of the /sup 14/C 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 /sup 3/H 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.

  10. Clinically employed opioid analgesics produce antinociception via μ-δ opioid receptor heteromers in Rhesus monkeys.

    Science.gov (United States)

    Yekkirala, Ajay S; Banks, Matthew L; Lunzer, Mary M; Negus, Stevens S; Rice, Kenner C; Portoghese, Philip S

    2012-09-19

    Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans.

  11. Monozygotic twinning in rhesus monkeys by manipulation of in vitro-derived embryos.

    Science.gov (United States)

    Mitalipov, Shoukhrat M; Yeoman, Richard R; Kuo, Hung-Chih; Wolf, Don P

    2002-05-01

    The nonhuman primate is a relevant model for human disease that can be used for diverse biomedical investigations. The ability to propagate a founder animal by application of assisted reproductive technologies is pressing, but an even greater need in many studies is access to genetically identical animals. In an effort to create genetically identical monkeys, we evaluated two approaches to monozygotic twinning; blastomere separation, and blastocyst bisection. Embryos were produced by intracytoplasmic sperm injection of oocytes recovered following controlled ovarian stimulation. The quality of demiembryos produced in these efforts was evaluated by quantitating the efficiency of creating identical pairs for embryo transfer, by morphological assessment, by the allocation of cells to the inner cell mass (ICM) and trophectoderm (TE) in the blastocyst, and by the outcome of embryo transfer to synchronized host animals. Pairs were produced in high yield (85%-95%) by both twinning methods. Demiembryos resulting from blastomere separations at the 2- or 4-cell stage grew to blastocysts at the control frequency. Demiblastocysts contained, on average, half the number of cells of the intact controls while maintaining the same ICM:TE or ICM:total cell ratio. The equivalency of demiblastocysts within a set was also evaluated by differential cell counting. Embryo transfers of identical sets led to a 33% clinical pregnancy rate, with two twin pregnancies initiated. Neither pregnancy resulted in term birth of monozygotic twins, but our results are sufficiently encouraging to justify a large-scale twinning trial in the rhesus macaque.

  12. The proinflammatory cytokine network: interactions in the CNS and blood of rhesus monkeys.

    Science.gov (United States)

    Reyes, T M; Coe, C L

    1998-01-01

    Proinflammatory cytokines [interleukin (IL)-1 and -6 and tumor necrosis factor-alpha] function within a complex network, stimulating the release of one another, as well as other cytokine agonists and antagonists. These interactions have not been as widely studied in vivo. Therefore, the following studies measured cytokines in blood and cerebrospinal fluid (CSF) from juvenile rhesus monkeys after intravenous administration of cytokines. IL-1 alpha and IL-1 beta were equally effective in elevating blood levels of IL-6. In contrast, IL-1 beta was the only cytokine that significantly elevated IL-6 levels in the CSF. Interestingly, both IL-1 and IL-6 increased levels of IL-1 receptor antagonist in the blood and comparably stimulated the release of cortisol. A second study confirmed that the IL-1-induced IL-6 in CSF was brain derived and not a result of diffusion from blood. This research extends studies of the cytokine cascade to the central nervous system (CNS), highlighting the brain response to peripheral activation.

  13. Architecture and connections of retrosplenial area 30 in the rhesus monkey (Macaca mulatta).

    Science.gov (United States)

    Morris, R; Petrides, M; Pandya, D N

    1999-07-01

    Because of the sharp curvature of the retrosplenial region around the splenium of the corpus callosum, standard coronal sections are not appropriate for architectonic analysis of its posteroventral part. In the present study, examination of the posteroventral retrosplenial region of the rhesus monkey in sections that were orthogonal to its axis of curvature (and therefore appropriate for architectonic analysis) has permitted definition of its architecture and precise extent. This analysis demonstrated that areas 29 and 30 of the retrosplenial cortex, as well as adjacent area 23 of the posterior cingulate cortex, extend together as an arch around the splenium of the corpus callosum and maintain their topographical relationship with one another throughout their entire course. Injections of anterograde and retrograde tracers confined to retrosplenial area 30 revealed that this area has reciprocal connections with adjacent areas 23, 19 and PGm, with the mid-dorsolateral part of the prefrontal cortex (areas 9, 9/46 and 46), with multimodal area TPO in the superior temporal sulcus, as well as the posterior parahippocampal cortex, the presubiculum and the entorhinal cortex. There are also bidirectional connections with the lateroposterior thalamic nucleus, as well as the laterodorsal and the anteroventral limbic thalamic nuclei. The connectivity of area 30 suggests that it may play a role in working memory processes subserved by the mid-dorsolateral frontal cortex in interaction with the hippocampal system.

  14. 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.

  15. Transient reinforcing effects of phenylisopropylamine and indolealkylamine hallucinogens in rhesus monkeys.

    Science.gov (United States)

    Fantegrossi, W E; Woods, J H; Winger, G

    2004-03-01

    Relatively few studies have assessed the reinforcing effects of hallucinogenic compounds, and no such studies have attempted to engender contingent responding for these compounds in animals with behavioral histories that include experience with serotonergically mediated reinforcing effects. The objectives of the present study were to investigate the capacity of several hallucinogenic compounds to maintain self-administration behavior in rhesus monkeys with a previous history of 3,4-methylenedioxymethamphetamine (MDMA) self-administration, and to compare these effects across a range of doses of drugs from two structural classes (indolealkylamines and phenylisopropylamines). The results indicate that no compound generated reliable responding and that no subject ever self-administered 4-iodo-2,5-dimethoxyphenylisopropylamine (DOI) at rates above those engendered by contingent saline. However, 3 out of 4 subjects did respond at rates between 0.75 and 3.0 responses/s in one or more sessions where N,N-dimethyltryptamine (DMT), mescaline or psilocybin were available. During some of these sessions in which self-administration was maintained, animals earned a majority of all available infusions and appeared intoxicated by the end of the session. This pattern of transient self-administration may indicate that these compounds have weak reinforcing effects, or mixed reinforcing and aversive effects.

  16. Delay discounting of food by rhesus monkeys: Cocaine and food choice in isomorphic and allomorphic situations.

    Science.gov (United States)

    Huskinson, Sally L; Woolverton, William L; Green, Leonard; Myerson, Joel; Freeman, Kevin B

    2015-06-01

    Research on delay discounting has focused largely on nondrug reinforcers in an isomorphic context in which choice is between alternatives that involve the same type of reinforcer. Less often, delay discounting has been studied with drug reinforcers in a more ecologically valid allomorphic context where choice is between alternatives involving different types of reinforcers. The present experiment is the first to examine discounting of drug and nondrug reinforcers in both isomorphic and allomorphic situations using a theoretical model (i.e., the hyperbolic discounting function) that allows for comparisons of discounting rates between reinforcer types and amounts. The goal of the current experiment was to examine discounting of a delayed, nondrug reinforcer (food) by male rhesus monkeys when the immediate alternative was either food (isomorphic situation) or cocaine (allomorphic situation). In addition, we sought to determine whether there was a magnitude effect with delayed food in the allomorphic situation. Choice of immediate food and immediate cocaine increased with amount and dose, respectively. Choice functions for immediate food and cocaine generally shifted leftward as delay increased. Compared to isomorphic situations in which food was the immediate alternative, delayed food was discounted more steeply in allomorphic situations where cocaine was the immediate alternative. Notably, discounting was not affected by the magnitude of the delayed reinforcer. These data indicate that how steeply a delayed nondrug reinforcer is discounted may depend more on the qualitative characteristics of the immediate reinforcer and less on the magnitude of the delayed one. (c) 2015 APA, all rights reserved).

  17. The frontal eye fields limit the capacity of visual short-term memory in rhesus monkeys.

    Science.gov (United States)

    Lee, Kyoung-Min; Ahn, Kyung-Ha

    2013-01-01

    The frontal eye fields (FEF) in rhesus monkeys have been implicated in visual short-term memory (VSTM) as well as control of visual attention. Here we examined the importance of the area in the VSTM capacity and the relationship between VSTM and attention, using the chemical inactivation technique and multi-target saccade tasks with or without the need of target-location memory. During FEF inactivation, serial saccades to targets defined by color contrast were unaffected, but saccades relying on short-term memory were impaired when the target count was at the capacity limit of VSTM. The memory impairment was specific to the FEF-coded retinotopic locations, and subject to competition among targets distributed across visual fields. These results together suggest that the FEF plays a crucial role during the entry of information into VSTM, by enabling attention deployment on targets to be remembered. In this view, the memory capacity results from the limited availability of attentional resources provided by FEF: The FEF can concurrently maintain only a limited number of activations to register the targets into memory. When lesions render part of the area unavailable for activation, the number would decrease, further reducing the capacity of VSTM.

  18. Acute brain metabolic effects of cocaine in rhesus monkeys with a history of cocaine use.

    Science.gov (United States)

    Henry, Porche' Kirkland; Murnane, Kevin S; Votaw, John R; Howell, Leonard L

    2010-12-01

    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 intravenous (i.v.) drug self-administration. PET imaging with F-18 labeled fluorodeoxyglucose (FDG) was used to measure acute intramuscular (i.m.) cocaine-induced changes in brain metabolism in the cocaine-naïve state, following 60 sessions under limited-access conditions (1 h/day), following 60 sessions under extended-access conditions (4 h/day), and following 4 weeks of drug withdrawal. In the cocaine-naïve state, cocaine-induced increases in brain metabolism were restricted to the prefrontal cortex. As cocaine exposure increased from limited to extended access, metabolic effects expanded throughout the frontal cortex and were induced within the striatum. Conversely, cocaine-induced activation was far less robust following withdrawal. The results highlight a progressive expansion of the metabolic effects of cocaine to include previously unaffected dopamine innervated brain regions as a consequence of cocaine self-administration history. The identification of brain regions progressively influenced by drug exposure may be highly relevant toward efforts to develop treatments for cocaine addiction.

  19. Transplacental pharmacokinetics of cocaine and benzoylecgonine in plasma and hair of rhesus monkeys.

    Science.gov (United States)

    Bailey, B; Morris, P; McMartin, K I; Klein, J; Duhart, H M; Gillam, M P; Binienda, Z; Slikker, W; Paule, M G; Koren, G

    1998-01-01

    There is large variability in the rate and extent of fetal damage from cocaine in humans; however, the sources of such variability are not presently known. In order to study the relationship between maternal cocaine pharmacokinetics at the end of pregnancy and maternal or infant cocaine and benzoylecgonine hair concentrations at birth, ten rhesus monkeys were administered cocaine intramuscularly throughout pregnancy. Cocaine and benzoylecgonine hair concentrations were determined at birth and correlated with maternal pharmacokinetics during pregnancy. There were no correlations between either maternal cocaine Cmax or AUC0-infinity and maternal and infant hair cocaine or benzoylecgonine concentrations. There were no significant correlations between maternal hair benzoylecgonine concentrations and either maternal benzoylecgonine AUC0-120 (r = 0.60; P = 0.07) or benzoylecgonine Cmax (r = 0.60; P = 0.07). No correlations existed between infant hair benzoylecgonine concentrations and either maternal benzoylecgonine AUC0-120 (r = 0.30; P = 0.40) or benzoylecgonine Cmax (r = 0.30; P = 0.40). Also, no correlation was found between maternal cocaine dose and maternal or infant cocaine and benzoylecgonine hair concentrations. In comparison to toxicants such as nicotine and carbon monoxide for which there is a good correlation between maternal systemic exposure and neonatal concentrations, the lack of a similar relationship for cocaine is consistent with the role of the placenta in contributing to the variability in the amounts of cocaine reaching the fetus and hence, potentially to the risk of adverse fetal outcome.

  20. 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.

  1. Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys.

    Science.gov (United States)

    Barouch, Dan H; Stephenson, Kathryn E; Borducchi, Erica N; Smith, Kaitlin; Stanley, Kelly; McNally, Anna G; Liu, Jinyan; Abbink, Peter; Maxfield, Lori F; Seaman, Michael S; Dugast, Anne-Sophie; Alter, Galit; Ferguson, Melissa; Li, Wenjun; Earl, Patricia L; Moss, Bernard; Giorgi, Elena E; Szinger, James J; Eller, Leigh Anne; Billings, Erik A; Rao, Mangala; Tovanabutra, Sodsai; Sanders-Buell, Eric; Weijtens, Mo; Pau, Maria G; Schuitemaker, Hanneke; Robb, Merlin L; Kim, Jerome H; Korber, Bette T; Michael, Nelson L

    2013-10-24

    The global diversity of HIV-1 represents a critical challenge facing HIV-1 vaccine development. HIV-1 mosaic antigens are bioinformatically optimized immunogens designed for improved coverage of HIV-1 diversity. However, the protective efficacy of such global HIV-1 vaccine antigens has not previously been evaluated. Here, we demonstrate the capacity of bivalent HIV-1 mosaic antigens to protect rhesus monkeys against acquisition of infection following heterologous challenges with the difficult-to-neutralize simian-human immunodeficiency virus SHIV-SF162P3. Adenovirus/poxvirus and adenovirus/adenovirus vector-based vaccines expressing HIV-1 mosaic Env, Gag, and Pol afforded a significant reduction in the per-exposure acquisition risk following repetitive, intrarectal SHIV-SF162P3 challenges. Protection against acquisition of infection correlated with vaccine-elicited binding, neutralizing, and functional nonneutralizing antibodies, suggesting that the coordinated activity of multiple antibody functions may contribute to protection against difficult-to-neutralize viruses. These data demonstrate the protective efficacy of HIV-1 mosaic antigens and suggest a potential strategy for the development of a global HIV-1 vaccine. PAPERCLIP:

  2. Effect of ionizing radiation on prostaglandin and gastric secretion in rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Dubois, A.; Dorval, E.D.; Steel, L.; Fiala, N.P.; Conklin, J.J.

    1987-01-01

    Early radiation toxicity is characterized by nausea and vomiting. The authors have previously shown that gastric emptying, gastric motility, and gastric secretion were suppressed after total-body exposure to irradiation. In this studies, the authors 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 /sup 60/Co 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-PGE determination) were not significantly modified by irradiation. In contrast, irradiation produced an immediate significant increase (P<0.05) in gastric-juice concentration of PGE2 and PGI2; 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.

  3. Characterization of the 10q26-orthologue in rhesus monkeys corroborates a functional connection between ARMS2 and HTRA1.

    Science.gov (United States)

    Pahl, Lisa; Spangenberg, Astrid; Schubert, Stephanie; Schönmann, Uwe; Schmidtke, Jörg; Stuhrmann, Manfred

    2012-05-01

    Age-related macular degeneration, which is the leading cause of blindness in industrialized countries, is a multifactorial, degenerative disorder of the macula with strong heritability. For age-related macular degeneration in humans, the genes ARMS2 and HTRA1 in the region 10q26 are both promising candidates for being involved in pathogenesis. However, the associated variants are located in a region of strong linkage disequilibrium and so far, the identification of the causative gene in humans was not yet possible. This dilemma might be solved using an appropriate model organism. Rhesus monkeys suffer from drusen, a major hallmark of age-related macular degeneration, and the drusen-phenotype shares susceptibility factors with human macular degeneration. Thus, the rhesus monkey represents a natural animal model to uncover genetic factors leading to macular degeneration. Moreover, the existence of genetically homogenous cohorts offers an excellent opportunity to determine risk factors. However, the 10q26-orthologue genomic region in rhesus monkeys is not characterized in detail so far. Therefore, the aim of this study is to analyze the rhesus linkage disequilibrium structure and to investigate whether variants in ARMS2 or HTRA1 are associated with the drusen-phenotype as well. We sequenced parts of a 20 kb region around ARMS2 and HTRA1 in a genetically homogeneous cohort of 91 rhesus monkeys descending from the CPRC rhesus cohort on Cayo Santiago and currently housed in the German Primate Centre in Göttingen. Within this group, ophthalmoscopic examinations revealed a naturally high drusen prevalence of about 47% in monkeys >5 years. We detected 56 genetic variants within and around ARMS2 and HTRA1 and, as one deviates from Hardy-Weinberg-Equilibrium, 55 polymorphisms were used to generate a linkage disequilibrium-Plot and to perform association studies. We observed strong linkage disequilibrium between the markers and were able to define two haplotype blocks. One of

  4. Immunogenicity and protective efficacy of a recombinant subunit West Nile virus vaccine in rhesus monkeys.

    Science.gov (United States)

    Lieberman, Michael M; Nerurkar, Vivek R; Luo, Haiyan; Cropp, Bruce; Carrion, Ricardo; de la Garza, Melissa; Coller, Beth-Ann; Clements, David; Ogata, Steven; Wong, Teri; Martyak, Tim; Weeks-Levy, Carolyn

    2009-09-01

    The immunogenicity and protective efficacy of a recombinant subunit West Nile virus (WNV) vaccine was evaluated in rhesus macaques (Macaca mulatta). The vaccine consisted of a recombinant envelope (E) protein truncated at the C-terminal end, resulting in a polypeptide containing 80% of the N-terminal amino acids of the native WNV protein (WN-80E), mixed with an adjuvant (GPI-0100). WN-80E was produced in a Drosophila melanogaster expression system with high yield and purified by immunoaffinity chromatography using a monoclonal antibody specific for flavivirus E proteins. Groups of monkeys were vaccinated with formulations containing 1 or 25 microg of WN-80E antigen, and both humoral and cellular immunity were assessed after vaccination. The results demonstrated potent antibody responses to vaccination, as determined by both enzyme-linked immunosorbent assay and virus-neutralizing antibody assays. All vaccinated animals responded favorably, and there was little difference in response between animals immunized with 1 or 25 microg of WN-80E. Cellular immunity was determined by lymphocyte proliferation and cytokine production assays using peripheral blood mononuclear cells from vaccinated animals stimulated in vitro with WN-80E. Cell-mediated immune responses varied from animal to animal within each group. About half of the animals responded with lymphoproliferation, cytokine production, or both. Again, there was little difference in response between animals immunized with a 1- or 25-microg dose of WN-80E in the vaccine formulations. In a separate experiment, groups of monkeys were immunized with the WN-80E/GPI-0100 vaccine or an adjuvant-only control formulation. Animals were then challenged by inoculation of wild-type WNV, and the level of viremia in each animal was monitored daily for 10 days. The results showed that whereas all animals in the control group had detectable viremia for at least 3 days after challenge, all of the vaccinated animals were negative on all

  5. Asymmetric generalization and interaction profiles in rhesus monkeys discriminating intravenous cocaine or intravenous heroin from vehicle.

    Science.gov (United States)

    Platt, Donna M; Rowlett, James K; Spealman, Roger D

    2010-03-01

    Many polydrug abusers combine cocaine with heroin in the form of a "speedball." This study investigated the discriminative stimulus (DS) effects of speedballs in rhesus monkeys trained to discriminate either intravenous cocaine or intravenous heroin from vehicle. Initial substitution tests revealed an asymmetry in the generalization profile of dopamine and opioid agonists such that mu agonists partially substituted for cocaine, but direct and indirect dopamine agonists did not substitute for heroin. Subsequent speedball tests in which drug mixtures were administered by coinjecting the component drugs while keeping the dose-ratio constant revealed an additional asymmetry. In cocaine-trained monkeys, coadministration of cocaine and heroin produced leftward shifts in the cocaine dose-response function. Heroin's cocaine-enhancing effects were mimicked by the mu agonists fentanyl and methadone and less consistently by the delta agonist (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC 80) and reversed by the mu antagonist naltrexone and the delta antagonist naltrindole. In heroin-trained monkeys, coadministration of cocaine and heroin attenuated the DS effects of heroin. Cocaine's heroin-attenuating effects were mimicked by the D1-like agonist 6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine (SKF 81297) and the D2-like agonist R-(-)-propylnorapomorphine and reversed by the D1-like antagonist (6aS-trans)-11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5H- benzo[d] aphtha[2,1-b]azepin-12-ol hydrobromide (SCH 39166) and the D2-like antagonist raclopride. Attenuation of the effects of heroin was accompanied by decreases in response rate. These results suggest that heroin enhances the DS effects of cocaine via mu, and to a lesser extent delta, receptor mechanisms; whereas cocaine-induced inhibition of the DS effects of heroin probably was due at least in part to masking of the heroin DS presumably

  6. Red Cell Alloimmunization to Rhesus Antigen Among Pregnant Women Attending a Tertiary Care Hospital in Oman

    Directory of Open Access Journals (Sweden)

    Tamima Al-Dughaishi

    2016-01-01

    Full Text Available Objectives: The detection of maternal alloimmunization against red cell antigens is vital in the management of hemolytic disease of the fetus and newborn. We sought to measure the presence of allosensitization to Rhesus D (RhD antibodies in antenatal women attending a tertiary care hospital and assess the fetal outcome in sensitized women. Methods: We conducted a retrospective review of pregnant Omani women who registered at the Sultan Qaboos University Hospital between June 2011 and June 2013. Pregnant women were tested for ABO blood type and were screened for RhD antigen and antibodies at their first antenatal clinic visit. In women who tested positive for the RhD antibodies, an antibody titer was performed to evaluate the severity of their case. Results: Data was available on 1,251 pregnant women who were managed and delivered at Sultan Qaboos University Hospital. The prevalence of RhD negative pregnant women was 7.3%. Blood group O was the most common followed by A, B, and AB. The rate of RhD negative alloimmunization was 10%, and anti-D was the most common antibody detected. There were no stillbirths or neonatal deaths. Postnatal transfusion was necessary for only one baby. Conclusions: The prevalence of RhD negativity was comparable to other Asian countries. Previous RhD alloimmunization and history of miscarriages were the most common maternal medical history.

  7. Reproducibility of Perfusion Parameters of Optic Disc and Macula in Rhesus Monkeys by Optical Coherence Tomography Angiography

    Institute of Scientific and Technical Information of China (English)

    Jing Li; Yi-Quan Yang; Di-Ya Yang; Xiang-Xiang Liu; Yun-Xiao Sun; Shi-Fei Wei; Ning-Li Wang

    2016-01-01

    Background:Optical coherence tomography (OCT) angiography is a novel technique by which we can detect the local perfusion of fundus directly.The aim of this study was to evaluate the reproducibility of optic disc and macular flow perfusion parameters in rhesus monkeys using OCT angiography.Methods:Eighteen healthy monkeys (18 eyes) were subjected to optic disc and macula flow index measurements via a high-speed and high-resolution spectral-domain OCT XR Avanti with a split-spectrum amplitude de-correlation angiography algorithm.Right eye was imaged 3 times during the first examination and once during each of the two following examinations.The intra-visit and inter-visit intraclass correlation coefficients (ICCs) were both determined.Results:The average flow indices of the four optic disc area layers were 0.171 ± 0.009 (optic nerve head),0.015 ± 0.004 (vitreous),0.052 ± 0.009 (radial peripapillary capillary),and 0.167 ± 0.011 (choroid).Average flow indices of the four macula area layers were 0.044 ± 0.011 (superficial retina),0.036 ± 0.011 (deep retina),0.016 ± 0.009 (outer retina),and 0.155 ± 0.013 (choroid).Intra-visit (ICC value:0.821-0.954) and inter-visit (ICC value:0.844-0.899) repeatability were both high.Conclusions:The study is about the reproducibility of optic disc and macular perfusion parameters as measured by OCT angiography in healthy rhesus monkeys.Flow index measurement reproducibility is high for both the optic disc and macula of normal monkey eyes.OCT angiography might be a useful technique to assess changes when examining monkeys with experimental ocular diseases.

  8. Effects of confined space and near vision stimulation on refractive status and vitreous chamber depth in adolescent rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    This study aimed to investigate the effects of sustained near vision stimulation,on the refractive development and elongation of the vitreous chamber in adolescent rhesus monkeys.A total of 12 adolescent rhesus monkeys(1.5-2.0 years old) were randomly assigned to 3 groups.In groups A(n=4) and B(n=4),monkeys were reared in close-vision cages for 8 and 4 h d-1,respectively;tiny granules were added on the cage floor to avoid visual deprivation and to encourage near gaze.In group C(n=4),monkeys were reared in open-vision cages,with non-granule food as a control.Vitreous chamber depth,refractive status,and corneal refractive power were assessed over 18 months.Paired t-test was used to compare the differences and a P-value<0.05 was considered to be statistically significant.In group A,vitreous chamber depth and optical axis elongated significantly,and refractive error shifted towards myopia during the observation period.In group B,vitreous chambers and optical axis elongated but the refractive power did not show significant changes.In group C,there was no significant elongation in vitreous chambers and optical axis,and the refractive power changed slightly towards hypermetropia.There were no significant changes in corneal refractive power in each group.Sustained near vision can promote vitreous chamber growth and induce myopic shifts in refractive power in adolescent monkeys.Our results demonstrate the potential for a primate model of near-work-related myopia.

  9. Recombinant poxvirus boosting of DNA-primed rhesus monkeys augments peak but not memory T lymphocyte responses.

    Science.gov (United States)

    Santra, Sampa; Barouch, Dan H; Korioth-Schmitz, Birgit; Lord, Carol I; Krivulka, Georgia R; Yu, Faye; Beddall, Margaret H; Gorgone, Darci A; Lifton, Michelle A; Miura, Ayako; Philippon, Valerie; Manson, Kelledy; Markham, Phillip D; Parrish, John; Kuroda, Marcelo J; Schmitz, Jörn E; Gelman, Rebecca S; Shiver, John W; Montefiori, David C; Panicali, Dennis; Letvin, Norman L

    2004-07-27

    Although a consensus has emerged that an HIV vaccine should elicit a cytotoxic T lymphocyte (CTL) response, the characteristics of an effective vaccine-induced T lymphocyte response remain unclear. We explored this issue in the simian human immunodeficiency virus/rhesus monkey model in the course of assessing the relative immunogenicity of vaccine regimens that included a cytokine-augmented plasmid DNA prime and a boost with DNA or recombinant pox vectors. Recombinant vaccinia virus, recombinant modified vaccinia Ankara (MVA), and recombinant fowlpox were comparable in their immunogenicity. Moreover, whereas the magnitude of the peak vaccine-elicited T lymphocyte responses in the recombinant pox virus-boosted monkeys was substantially greater than that seen in the monkeys immunized with plasmid DNA alone, the magnitudes of recombinant pox boosted CTL responses decayed rapidly and were comparable to those of the DNA-alone-vaccinated monkeys by the time of viral challenge. Consistent with these comparable memory T cell responses, the clinical protection seen in all groups of experimentally vaccinated monkeys was similar. This study, therefore, indicates that the steady-state memory, rather than the peak effector vaccine-elicited T lymphocyte responses, may be the critical immune correlate of protection for a CTL-based HIV vaccine.

  10. Use of enclosures with functional vertical space by captive rhesus monkeys (Macaca mulatta) involved in biomedical research.

    Science.gov (United States)

    Clarence, Wendy M; Scott, Jennifer P; Dorris, Michael C; Paré, Martin

    2006-09-01

    We assessed space use by 2 pairs of captive female rhesus monkeys recently transferred into 2 enclosures moderately larger than their former traditional research cages and providing elevated perches at or above human eye level for all monkeys. This new space did not affect the ongoing biomedical research in which these captive monkeys were involved, and we sought to determine whether they used the elevated positions preferentially, as do wild animals. The frequency and duration of visits at each of the 9 distinct regions within these enclosures was calculated during 30-min morning and evening sessions over 20 d. We found that the monkeys frequented all regions of their enclosures in a similar manner during both morning and evening sessions. However, the duration spent at each region varied significantly between morning and evening sessions, with high perches being chosen preferentially in the evenings. Overall, the monkeys spent the majority of their time at elevated positions. These results support the view that access to functional vertical space provides a preferred environment for species- specific behavior and is an option that should be considered by other research facilities.

  11. Expression of gelatinases and tissue inhibitors of metallo- proteinases in the rhesus monkey (Macaca mulatta) corpus luteum

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are believed to play important roles in the formation and regression of corpus luteum (CL). This study is to investigate the expression of gelatinases (MMP-2, -9) and TIMPs in the rhesus monkey CL in both early and late luteal phases and during the early stages of pregnancy. Ovaries were collected from regularly cycling rhesus monkey at D5 and D15 following ovulation and at D12, D18 and D26 of pregnancy. In situ hybridization revealed that in the CL MMP-2 mRNA was expressed during both formation and regression, while MMP-9 mRNA was mainly localized in the late luteal phase. Reduction of MMP-2, -9 transcripts in the CL was observed during pregnancy. MMP-2 mRNA in the CL reduced to an undetectable level at D26 of pregnancy. TIMP-1 mRNA was highly expressed in the CL in both early and late luteal phases and persisted throughout the early stages of pregnancy. Strong signal for TIMP-2 mRNA was also detected in both luteal phases, and the level of TIMP-2 mRNA gradually increased with the progresses of pregnancy. No TIMP-3 mRNA was detected in the macaque CL in this study. In conclusion, these results suggest that MMP-2, -9 and TIMP-1, -2 may have functional roles in rhesus monkey CL. Coordinated expression of MMP-2, -9 and TIMP-2 may play a role in the maintaining of luteal function during early pregnancy. The unchanged expression pattern of TIMP-1 indicates that it may have other functions in the primate CL than inhibition of MMPs.

  12. Assessing the Value of Television as Environmental Enrichment for Individually Housed Rhesus Monkeys: A Behavioral Economic Approach.

    Science.gov (United States)

    Harris, Linda D.; Briand, Edward J.; Orth, Rushawn; Galbicka, Gregory

    1999-03-01

    The goal of this study was to evaluate television as a source of environmental enrichment for individually housed rhesus monkeys (Macaca mulatta) by using the concepts of behavioral economics. Phase I entailed the use of operant conditioning to assess the behavior of eight rhesus monkeys given the opportunity to control their environment through lever activation of a television (TV). Success in shaping was variable, and only two animals successfully acquired lever pressing. Phase II used an alternating reinforcement/ extinction procedure as a control method to determine the degree to which lever pressing depended on TV presentation. Both animals responded with more lever pressing on the days when lever pressing produced TV. The first animal, tested with the alternating reinforcement/extinction procedure for 12 weeks yielded a mean significant difference of 3.85 (p = 0.036); the second assessed for 9 weeks was associated with a mean significant difference of 6.0 (p = 0.018). Therefore, TV (and not lever pressing itself) was positively reinforcing. The final phase of the study progressively increased the fixed ratio (FR) from 1 to 8. Linear regression of the data points, plotted as the log of price (or FR) vs the consumption of TV, revealed a significantly negative slope (-2.179, p, 0.05) and accounted for 89% of the variance. The negative demand curve suggested that TV is not a valued commodity and is highly elastic. TV provided to individually housed rhesus monkeys appears to be a weakly positive reinforcer for some animals, which may contribute to overall environmental enrichment.

  13. Effect of input multiplicity on the establishment of simian virus 40 persistent infections in rhesus monkey kidney cells.

    Science.gov (United States)

    Norkin, L C

    1977-12-01

    Monolayer cultures of LLC-MK2 rhesus monkey kidney cells become persistently infected with simian virus 40 after infection at input multiplicities of 100, 10, or 1 plaque-forming unit per cell. After 3 weeks, all cells of the cultures infected at a multiplicity of 1 plaque-forming unit per cell produced the simian virus 40 T antigen. In contrast, 8 to 11 weeks elapsed before all the cells in the cultures infected at a multiplicity of 100 plaque-forming units per cell produced T antigen. Defective interfering particles and interferon production were not evident during this time.

  14. Lack of cleavage of immunoglobulin A (IgA) from rhesus monkeys by bacterial IgA1 proteases.

    OpenAIRE

    Reinholdt, J; Kilian, M.

    1991-01-01

    Bacterial immunoglobulin A1 (IgA1) proteases cleaving IgA1 and secretory IgA1 molecules in the hinge region are believed to be important virulence factors. Previous studies have indicated that IgA of humans, gorillas, and chimpanzees are the exclusive substrates of these enzymes. In a recent study, IgA from the rhesus monkey was found to be susceptible to the IgA1 protease activity of Streptococcus pneumoniae. In an attempt to reproduce this observation, we found that neither five isolates of...

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

    Energy Technology Data Exchange (ETDEWEB)

    Petrides, M.; Pandya, D.N.

    1988-07-01

    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.

  16. Low temperature storage of rhesus monkey spermatozoa and fertility evaluation by intracytoplasmic injection.

    Science.gov (United States)

    Yeoman, Richard R; Mitalipov, Shoukhrat; Gerami-Naini, Behzad; Nusser, Kevin D; Wolf, Don P

    2005-06-01

    The objective was to develop a sperm freezing procedure suitable for use in the propagation of valuable founder animals by assisted reproductive technologies. Here, we report a comparison of processing methods by measuring the motility of fresh and frozen-thawed rhesus monkey spermatozoa and fertility via intracytoplasmic spermatozoa injection (ICSI) of sibling oocytes. Washed spermatozoa were frozen in straws or in pellets using different cryoprotective media and processed post-thaw with or without a density gradient centrifugation step. Among the four study series, motility post-thaw was improved with density gradient centrifugation (17-24% versus 75%, P<0.01) achieving levels similar to fresh spermatozoa. Spermatozoa injected oocytes (total n=377) were co-cultured on BRL cells and observed for fertilization and development. With spermatozoa frozen in straws in liquid nitrogen vapors, the fertilization rate after ICSI was lower than with fresh spermatozoa (40-44% versus 77-86%, P<0.05), even with the Percoll-enriched fraction that exhibited robust motility. In contrast, somewhat slower freezing of spermatozoa in pellets on dry ice supported fertilization rates (73%) that were similar to the fresh counterpart. Developmental rates of fertilized eggs were similar in all experiments. A total of 106 embryo transfers has resulted in the first primate born after ICSI with F/T ejaculated spermatozoa plus 22 other infants to date. Additionally, a 3-4 h incubation after thawing improved the fertilization rate with spermatozoa from a male with poor post-thaw recovery of sperm motility. In conclusion, an acceptable fertilization rate after ICSI with motile, frozen-thawed primate spermatozoa was observed comparable to that obtained with fresh spermatozoa allowing small quantities of competent spermatozoa to be used with ICSI to facilitate propagation of desirable primate genotypes.

  17. 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.

  18. Effects of L-methamphetamine treatment on cocaine- and food-maintained behavior in rhesus monkeys.

    Science.gov (United States)

    Kohut, Stephen J; Bergman, Jack; Blough, Bruce E

    2016-03-01

    Monoamine releasers with prominent dopaminergic actions, e.g., D-methamphetamine (D-MA), significantly reduce cocaine use and craving in clinical and preclinical laboratory studies. However, D-MA and related drugs also display high abuse potential, which limits their acceptability as agonist replacement medications for the management of Cocaine Use Disorder. The L-isomer of methamphetamine (L-MA), unlike D-MA, has preferential noradrenergic actions and is used medicinally with low, if any, abuse liability. The present study was conducted to determine whether L-MA could serve as an agonist replacement medication by both mimicking interoceptive effects of cocaine and decreasing intravenous (IV) cocaine self-administration. Separate groups (N = 4-5) of rhesus monkeys were studied to determine whether L-MA could (1) substitute for cocaine in subjects that discriminated intramuscular (IM) cocaine (0.4 mg/kg) from saline and (2) decrease IV cocaine self-administration under a second-order FR2(VR16:S) schedule of reinforcement. L-MA, like D-MA but with approximately 5-fold lesser potency, substituted for cocaine in drug discrimination experiments in a dose-dependent manner. In IV self-administration studies, 5-10-day treatments with continuously infused L-MA (0.032-0.32 mg/kg/h, IV) dose-dependently decreased cocaine-maintained responding; the highest dosage reduced cocaine intake to levels of saline self-administration without appreciable effects on food-maintained responding. These results indicate that L-MA both shares discriminative stimulus effects with cocaine and reduces cocaine self-administration in a behaviorally selective manner. L-MA and other compounds with a similar pharmacological profile deserve further evaluation for the management of Cocaine Use Disorder.

  19. 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.

  20. Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of age and gender

    Science.gov (United States)

    Cahoon, S.; Boden, S. D.; Gould, K. G.; Vailas, A. C.

    1996-01-01

    Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15-20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non

  1. Body weight decreases induced by estradiol in female rhesus monkeys are dependent upon social status

    Science.gov (United States)

    Michopoulos, Vasiliki; Wilson, Mark E.

    2010-01-01

    Gonadal steroids regulate appetite and thus body weight. In addition, continuous exposure to stressors negatively influences appetite through circuits likely distinct from those of gonadal steroids. The occurrence of adverse metabolic consequences due to chronic exposure to psychosocial stressors is twice as frequent in women as men, implicating a role for ovarian hormones, estradiol (E2) and progesterone (P4), in modulating stress-induced changes in appetite. Using social subordination in female macaques as a model of social stress, the current study tested the hypothesis that subordinate females would lose more weight during E2 treatment and gain less weight during P4 administration than dominant females. Because polymorphisms in the gene encoding the serotonin transporter (5HTT; SCL6A4) are known to alter responsivity to stress, we hypothesized that weight loss during E2 administration would be greatest in females with the short variant (s-variant) allele of 5HTT. Dominant females were significantly heavier than subordinate animals throughout the study, a result consistent with previous accounts of food intake when animals are fed a low-fat, high-fiber diet. Females with the s-variant 5HTT genotype weighed significantly less than l/l animals. Dominant animals lost significantly more weight than subordinate animals during E2 treatment. Administration of P4 blocked the weight-reducing effects of E2 in all females, regardless of social status. These data provide evidence that social subordination modulates the influence of ovarian steroid hormones on body weight in female rhesus monkeys independent of 5HTT genotype. Given the prosocial effects of these steroids, future studies are necessary to determine whether status differences in E2-induced weight loss are due to diminished food intake and or increases in energy expenditure and how the change in energy availability during E2 treatments relates to a female’s motivation to interact with conspecifics. PMID

  2. 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.; Baraskaus, 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

    2016-01-01

    Summary The most recent Ebola virus outbreak in West Africa – 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 sequelae1. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we describe the discovery of a novel anti-EBOV small molecule antiviral, GS-5734, a monophosphoramidate prodrug of an adenosine analog. GS-5734 exhibits antiviral activity against multiple variants of EBOV 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 alternate substrate and RNA-chain terminator in primer-extension assays utilizing 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, eye, and brain. In a rhesus monkey model of EVD, once daily intravenous administration of 10 mg/kg 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 of six treated animals. These results provide 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 potential for expanded indications

  3. 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.

  4. 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.

  5. Extensive Spinal Decussation and Bilateral Termination of Cervical Corticospinal Projections in Rhesus Monkeys

    Science.gov (United States)

    Rosenzweig, Ephron S.; Brock, John H.; Culbertson, Maya D.; Lu, Paul; Moseanko, Rod; Edgerton, V. Reggie; Havton, Leif A.; Tuszynski, Mark H.

    2009-01-01

    To examine neuroanatomical mechanisms underlying fine motor control of the primate hand, adult Rhesus monkeys underwent injections of biotinylated dextran amine (BDA) into the right motor cortex. Spinal axonal anatomy was examined using detailed serial-section reconstruction and modified stereological quantification. 87% of corticospinal tract (CST) axons decussated in the medullary pyramids and descended through the contralateral dorsolateral tract of the spinal cord. 11% of CST axons projected through the dorsolateral CST ipsilateral to the hemisphere of origin, and 2% of axons projected through the ipsilateral ventromedial CST. Notably, corticospinal axons decussated extensively across the spinal cord midline. Remarkably, nearly two-fold more CST axons decussated across the cervical spinal cord midline (~12,000 axons) than were labeled in all descending components of the CST (~6,700 axons). These findings suggest that CST axons extend multiple segmental collaterals. Furthermore, serial-section reconstructions revealed that individual axons descending in either the ipsilateral or contralateral dorsolateral CST can: 1) terminate in the gray matter ipsilateral to the hemisphere of origin; 2) terminate in the gray matter contralateral to the hemisphere of origin; or 3) branch in the spinal cord and terminate on both sides of the spinal cord. These results reveal a previously unappreciated degree of bilaterality and complexity of corticospinal projections in the primate spinal cord. This bilaterality is more extensive than that of the rat CST, and may resemble human CST organization. Thus, augmentation of sprouting of these extensive bilateral CST projections may provide a novel target for enhancing recovery after spinal cord injury. PMID:19125408

  6. Use of primary cell cultures to measure the late effects in the skins of rhesus monkeys irradiated with protons

    Science.gov (United States)

    Cox, A. B.; Wood, D. H.; Lett, J. T.

    Previous pilot investigations of the uses of primary cell cultures to study late damage in stem cells of the skin of the New Zealand white (NZW) rabbit and the rhesus monkey /1-3/, have been extended to individual monkeys exposed to 55 MeV protons. Protons of this energy have a larger range in tissue of (~2.6 cm) than the 32 MeV protons (~0.9 cm) to which the animals in our earlier studies had been exposed. Although the primary emphases in the current studies were improvement and simplification in the techniques and logistics of transportation of biopsies to a central analytical facility, comparison of the quantitative measurements obtained thus far for survival of stem cells in the skins from animals irradiated 21 years ago reveals that the effects of both proton energies are similar.

  7. Radiation-released histamine in the rhesus monkey as modified by mast cell depletion and antihistamine. Scientific report

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, T.F.; Strike, T.A.

    1975-06-01

    Changes in blood histamine concentrations of rhesus monkeys were measured after a 4000-rad dose of mixed gamma-neutron radiation. All animals were pretreated with amino-guanidine to retard histamine catabolism. Histamine concentrations increased from 26 + or - 13.5 to 235 + or - 16 ng/ml after irradiation. When the animals were pretreated with an antihistamine, chlorpheniramine (3 mg/kg), histamine concentrations changed from 25.7 + or - 13.5 to 462 + or - 226 ng/ml after irradiation. When the monkeys were pretreated with a specific mast cell histamine depleter, compound 48/80 (1mg/kg per day) for four consecutive days and then irradiated (4000 rads), histamine concentrations did not change significantly. When 48/80 was given 20 min after irradiation, histamine concentrations changed from 18 + or - 2 ng/ml to a maximum of 35 + or - 9 ng/ml after 48/80 injection. (Author) (GRA)

  8. Mortality in Captive Rhesus Monkeys (Macaca mulatta) in China Due to Infection with Yersinia pseudotuberculosis Serotype O:1a.

    Science.gov (United States)

    Zhao, Na; Li, Meng; Amer, Said; Liu, Shelan; Luo, Jing; Wang, Shan; He, Hongxuan

    2016-09-01

    The most common serotypes of Yersinia pseudotuberculosis infecting non-human primates are serotypes O:1b, O:3, O:4, and O:7. The O:1a serotype has never been reported in non-human primates. The present study describes an outbreak of serotype O:1a with high fatality (6/18) in captive rhesus monkeys in China. Bacteria were isolated from different organs of the carcasses using standard microbiological procedures. The strain was identified using conventional and molecular techniques such as morphological and biochemical identification, serotype determination, PCR-sequence analysis based on the 16S rRNA gene, detection of virulence genes, and antimicrobial susceptibility testing. The pathogenicity was determined after experimental infection in mice. Taken together, the obtained data indicate that Y. pseudotuberculosis O:1a is a pathogen of concern and represents a potential threat to monkey conservation efforts.

  9. Age-related changes in dentate gyrus cell numbers, neurogenesis, and associations with cognitive impairments in the rhesus monkey

    Directory of Open Access Journals (Sweden)

    Laura Benjamin Ngwenya

    2015-07-01

    Full Text Available The generation of new neurons in the adult mammalian brain is well established for the hippocampal dentate gyrus. However, the role of neurogenesis in hippocampal function and cognition, how it changes in aging, and the mechanisms underlying this are yet to be elucidated in the monkey brain. To address this, we investigated adult neurogenesis in the dentate gyrus of 42 rhesus monkeys (39 cognitively tested ranging in age from young adult to the elderly. We report here that there is an age-related decline in proliferation and a delayed development of adult neuronal phenotype. Additionally, we show that many of the new neurons survive throughout the lifetime of the animal and may contribute to a modest increase in total neuron number in the granule cell layer of the dentate gyrus over the adult life span. Lastly, we find that measures of decreased adult neurogenesis are only modestly predictive of age-related cognitive impairment.

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

    Directory of Open Access Journals (Sweden)

    Jing Li

    Full Text Available To study the normal values of the retinal oxygen saturation in Rhesus monkeys and to evaluated repeatability and reproducibility of retinal oxygen saturation measurements.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 examination, each eye was imaged three times. At the following two examinations, each eye was imaged once. All examinations were finished in one month. P values were calculated to evaluate the difference between the measurements during three visits by performing an ANOVA. Intra-visit and inter-visit intraclass correlation coefficient (ICC was determined.At baseline, the average SaO2 and SvO2 were 89.48 ± 2.64% and 54.85 ± 2.18%, respectively. The global A-V difference was 34.63 ± 1.91%. The difference between the three visits was not significant (p>0.05. The highest A-V difference in SO2 and lowest saturations were found in the inferotemporal quadrant. Intra-session and inter-visit repeatability were both high. For all oxygen saturation parameters, the ICC values of the intra-session repeatability ranged between 0.92 and 0.96. As found previously, a relatively high ICC value for inter-visit repeatability also was found for all oxygen saturation measurements, ranging between 0.86 and 0.94, with the lowest values in the infero-nasal quadrant.Our study is the first to describe retinal SO2 in healthy Rhesus monkeys. In normal monkey eyes, the reproducibility and repeatability of retinal oximetry oxygen saturation measurements were high in the retinal arterioles and venules. Our results support that Oxymap T1 retinal oximetry is a suitable and reliable technique in monkey studies.

  11. Swine Influenza Virus Vaccine: Potentiation in Rhesus Monkeys of Antibody Responses by a Nuclease Resistant Derivative of Poly I.Poly C

    Science.gov (United States)

    1976-10-04

    with poly-l-lysine and carboxymethylcellulose (poly ICLC) enhances the antibody response in rhesus monkeys immunized with swine influenza virus...of poly I-poly C with poly-l-lysine and carboxymethylcellulose (poly ICLC) has been shown to be a much more effective interferon inducer in primates...influenza subunit antigen prepared from the A/New Jersey/76 (swine) strain of virus, when tested in monkeys. Monovalent influenza virus subunit

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

    Energy Technology Data Exchange (ETDEWEB)

    Hill, F.S.; Cantu, A.O.; Lucas, J.N. (Lawrence Livermore National Lab., CA (United States)); Cox, A.B.; Salmon, Y.L. (Air Force Armstrong Lab., Brookes AFB, TX (United States))

    1994-10-01

    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 [mu]g/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 < 0.001) that that produced by PHA (M1<0.01) in lymphocytes from the same 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. (author).

  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. 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.

  15. Bone growth in juvenile rhesus monkeys is influenced by 5HTTLPR polymorphisms and interactions between 5HTTLPR polymorphisms and fluoxetine.

    Science.gov (United States)

    Golub, Mari S; Bulleri, Alicia M; Hogrefe, Casey E; Sherwood, Richard J

    2015-10-01

    Male rhesus monkeys received a therapeutic oral dose of the selective serotonin reuptake inhibitor (SSRI) fluoxetine daily from 1 to 3 years of age. Puberty is typically initiated between 2 and 3 years of age in male rhesus and reproductive maturity is reached at 4 years. The study group was genotyped for polymorphisms in the monoamine oxidase A (MAOA) and serotonin transporter (SERT) genes that affect serotonin neurotransmission. Growth was assessed with morphometrics at 4 month intervals and radiographs of long bones were taken at 12 month intervals to evaluate skeletal growth and maturation. No effects of fluoxetine, or MAOA or SERT genotype were found for growth during the first year of the study. Linear growth began to slow during the second year of the study and serotonin reuptake transporter (SERT) long polymorphic region (5HTTLPR) polymorphism effects with drug interactions emerged. Monkeys with two SERT 5HTTLPR L alleles (LL, putative greater transcription) had 25-39% less long bone growth, depending on the bone, than monkeys with one S and one L allele (SL). More advanced skeletal maturity was also seen in the LL group, suggesting earlier onset of puberty. An interaction between 5HTTLPR polymorphisms and fluoxetine was identified for femur and tibia growth; the 5HTTLPR effect was seen in controls (40% less growth for LL) but not in the fluoxetine treated group (10% less growth for LL). A role for serotonin in peripubertal skeletal growth and maturation has not previously been investigated but may be relevant to treatment of children with SSRIs.

  16. Circadian force and EMG activity in hindlimb muscles of rhesus monkeys

    Science.gov (United States)

    Hodgson, J. A.; Wichayanuparp, S.; Recktenwald, M. R.; Roy, R. R.; McCall, G.; Day, M. K.; Washburn, D.; Fanton, J. W.; Kozlovskaya, I.; Edgerton, V. R.; Rumbaugh, D. M. (Principal Investigator)

    2001-01-01

    Continuous intramuscular electromyograms (EMGs) were recorded from the soleus (Sol), medial gastrocnemius (MG), tibialis anterior (TA), and vastus lateralis (VL) muscles of Rhesus during normal cage activity throughout 24-h periods and also during treadmill locomotion. Daily levels of MG tendon force and EMG activity were obtained from five monkeys with partial datasets from three other animals. Activity levels correlated with the light-dark cycle with peak activities in most muscles occurring between 08:00 and 10:00. The lowest levels of activity generally occurred between 22:00 and 02:00. Daily EMG integrals ranged from 19 mV/s in one TA muscle to 3339 mV/s in one Sol muscle: average values were 1245 (Sol), 90 (MG), 65 (TA), and 209 (VL) mV/s. The average Sol EMG amplitude per 24-h period was 14 microV, compared with 246 microV for a short burst of locomotion. Mean EMG amplitudes for the Sol, MG, TA, and VL during active periods were 102, 18, 20, and 33 microV, respectively. EMG amplitudes that approximated recruitment of all fibers within a muscle occurred for 5-40 s/day in all muscles. The duration of daily activation was greatest in the Sol [151 +/- 45 (SE) min] and shortest in the TA (61 +/- 19 min). The results show that even a "postural" muscle such as the Sol was active for only approximately 9% of the day, whereas less active muscles were active for approximately 4% of the day. MG tendon forces were generally very low, consistent with the MG EMG data but occasionally reached levels close to estimates of the maximum force generating potential of the muscle. The Sol and TA activities were mutually exclusive, except at very low levels, suggesting very little coactivation of these antagonistic muscles. In contrast, the MG activity usually accompanied Sol activity suggesting that the MG was rarely used in the absence of Sol activation. The results clearly demonstrate a wide range of activation levels among muscles of the same animal as well as among different

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

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    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.

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

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    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

  19. Standardized assessment of NAb responses elicited in rhesus monkeys immunized with single- or multi-clade HIV-1 envelope immunogens.

    Science.gov (United States)

    Seaman, Michael S; Leblanc, Daniel F; Grandpre, Lauren E; Bartman, Melissa T; Montefiori, David C; Letvin, Norman L; Mascola, John R

    2007-10-10

    The genetic diversity of HIV-1 envelope glycoproteins (Env) remains a major obstacle to the development of an antibody-based AIDS vaccine. The present studies examine the breadth and magnitude of neutralizing antibody (NAb) responses in rhesus monkeys after immunization with DNA prime-recombinant adenovirus (rAd) boost vaccines encoding either single or multiple genetically distant Env immunogens, and subsequently challenged with a pathogenic simian-human immunodeficiency virus (SHIV-89.6P). Using a standardized multi-tier panel of reference Env pseudoviruses for NAb assessment, we show that monkeys immunized with a mixture of Env immunogens (clades A, B, and C) exhibited a greater breadth of NAb activity against neutralization-sensitive Tier 1 viruses following both vaccination and challenge compared to monkeys immunized with a single Env immunogen (clade B or C). However, all groups of Env-vaccinated monkeys demonstrated only limited neutralizing activity against Tier 2 pseudoviruses, which are more characteristic of the neutralization sensitivity of circulating HIV-1. Notably, the development of a post-challenge NAb response against SHIV-89.6P was similar in monkeys receiving either clade B, clade C, or clade A+B+C Env immunogens, suggesting cross-clade priming of NAb responses. In addition, vaccines encoding Env immunogens heterologous to SHIV-89.6P primed for a rapid anamnestic NAb response following infection compared to vaccines lacking an Env component. These results show that DNA/rAd immunization with multiple diverse Env immunogens is a viable approach for enhancing the breadth of NAb responses against HIV-1, and suggest that Env immunogens can prime for anamnestic NAb responses against a heterologous challenge virus.

  20. Population variation in neuroendocrine activity is associated with behavioral inhibition and hemispheric brain structure in young rhesus monkeys.

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    Short, Sarah J; Lubach, Gabriele R; Shirtcliff, Elizabeth A; Styner, Martin A; Gilmore, John H; Coe, Christopher L

    2014-09-01

    Population variation in hypothalamic-pituitary-adrenal (HPA) activity and reactivity was assessed in a healthy sample of 48 juvenile rhesus monkeys. Cluster analysis of the HPA profiles revealed four distinct neuroendocrine phenotypes based on six indices of HPA functioning. Behavioral reactivity was also evaluated in response to novel stimuli, and revealed marked differences between animals in the highest- and lowest-cortisol clusters. Specifically, animals in the high-cortisol cluster showed larger stress-induced cortisol responses and blunted feedback sensitivity to dexamethasone. They were also emotionally reactive, displayed more aggressive behaviors, and were less likely to approach novel objects. In contrast, monkeys in the low-cortisol cluster were more likely to approach and explore novel objects. Representative animals with high or low cortisol profiles were scanned with Magnetic Resonance Imaging to evaluate structural differences in global and regional gray matter (GM) and white matter (WM) volumes. Monkeys with higher cortisol reactivity evinced less hemispheric brain asymmetry, due to decreased GM in the right hemisphere. Stress reactivity was inversely related to global GM and positively related to total cerebrospinal fluid volume. This inverse relationship was also observed in several stress-sensitive regions, including prefrontal and frontal cortices. Our study demonstrates that population variation in pituitary-adrenal activity is related to behavioral disposition and cerebral structure in this nonhuman primate species.

  1. Heterogeneous afferents to the inferior parietal lobule of the rhesus monkey revealed by the retrograde transport method.

    Science.gov (United States)

    Divac, I; Lavail, J H; Rakic, P; Winston, K R

    1977-03-11

    The sources of afferent connections to the inferior parietal lobule (rostral part of the area 7 of Brodman; PF and rostral part of PG of von Bonin and Bailey) were examined with the retrograde transport method in infant and adult rhesus monkeys. Two to 3 days after injections of horseradish peroxidase (HRP) into the cortex, the animals were anesthetized, and the brains fixed and processed for the histochemical demonstration of the enzyme marker. Labeled neurons were found in layer III in the ipsilateral prefrontal, parietal, occipital and temporal cortices, notably in areas 5, 19, 22 and 46 of Brodmann, and in area 7 of the contralateral parietal cortex. In the thalamus, HRP-positive cells were located ipsilaterally in the medial pulvinar nucleus in the nuclei centrum medianum and parafascicularis, as well as in the rostral thalamus, lateral and medial to the mammillothalamic tract, in the nucleus ventralis anterior and nucleus paracentralis. Numerous labeled cells were also identified in the magnocellular nuclei of the basal forebrain, in the dorsal and medial raphe nuclei, and in the locus coeruleus. Most of the cells in these regions were located in the hemisphere ipsilateral to the injections, but a number of them were also found in the contralateral hemispher. In adult monkeys, brownish granules in the cytoplasm of some cells were interpreted as endogenous pigment or due to various pigment precursors. However, all 14 locations listed above were identified in the infant monkey in which endogenous pigment was not a confounding factor.

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

    Science.gov (United States)

    Dettmer, Amanda M; Rosenberg, Kendra L; Suomi, Stephen J; Meyer, Jerrold S; Novak, Melinda A

    2015-01-01

    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 (ppregnancy and lactation for all monkeys (phormonal profiles and infant development. These effects may, in part, reflect differential reproductive and maternal effort in mothers with varied caretaking experience. In addition, infant exposure to relatively higher levels of maternal cortisol during the late fetal and early postnatal periods is predictive of poorer developmental outcomes.

  3. Loss of D2 receptor binding with age in rhesus monkeys: importance of correction for differences in striatal size.

    Science.gov (United States)

    Morris, E D; Chefer, S I; Lane, M A; Muzic, R F; Wong, D F; Dannals, R F; Matochik, J A; Bonab, A A; Villemagne, V L; Grant, S J; Ingram, D K; Roth, G S; London, E D

    1999-02-01

    The relation between striatal dopamine D2 receptor binding and aging was investigated in rhesus monkeys with PET. Monkeys (n = 18, 39 to 360 months of age) were scanned with 11C-raclopride; binding potential in the striatum was estimated graphically. Because our magnetic resonance imaging analysis revealed a concomitant relation between size of striatum and age, the dynamic positron emission tomography (PET) data were corrected for possible partial volume (PV) artifacts before parameter estimation. The age-related decline in binding potential was 1% per year and was smaller than the apparent effect if the age-related change in size was ignored. This is the first in vivo demonstration of a decline in dopamine receptor binding in nonhuman primates. The rate of decline in binding potential is consistent with in vitro findings in monkeys but smaller than what has been measured previously in humans using PET. Previous PET studies in humans, however, have not corrected for PV error, although a decline in striatal size with age has been demonstrated. The results of this study suggest that PV correction must be applied to PET data to accurately detect small changes in receptor binding that may occur in parallel with structural changes in the brain.

  4. Gonadal and nongonadal mechanisms contribute to the prepubertal hiatus in gonadotropin secretion in the female rhesus monkey (Macaca mulatta).

    Science.gov (United States)

    Pohl, C R; deRidder, C M; Plant, T M

    1995-07-01

    The present study reexamined the role of the ovary in determining the prepubertal hiatus of gonadotropin secretion in the rhesus monkey. Day- and nighttime blood samples were obtained weekly from neonatally (7-10 days of age) ovariectomized and intact monkeys from birth until 3 yr of age. In the intact monkeys, plasma FSH levels increased during the first month of life, remained elevated until approximately 3 months of age, and then decreased to become undetectable by 7 months of age. Thereafter, plasma FSH remained undetectable until approximately 19 months of age, at which time it again increased to detectable concentrations. In animals ovariectomized as neonates, the developmental pattern in FSH secretion was similar to that in intact animals, but, quantitatively, mean plasma FSH concentrations in the agonadal females were greater than those in the intact control group at all times. Circulating daytime LH concentrations in intact animals were generally below the sensitivity of the assay during the neonatal and prepubertal phases of development, but after 27 months of age, this plasma hormone was measurable on occasion. In neonatally ovariectomized monkeys, daytime LH was elevated during the first month of life, undetectable between 2-20 months of age, and then rose into the adult range by the end of the study. Nocturnal plasma FSH and LH concentrations in agonadal monkeys were generally greater than those during the day at all stages of development. Of particular note was the finding that during the prepubertal hiatus in gonadotropin secretion, when daytime LH levels were mostly immeasurable, nighttime levels of this gonadotropin were consistently elevated. The hypersecretion of gonadotropin during prepubertal development in agonadal animals also occurred when ovariectomy was performed at 61-62 weeks of age. These findings demonstrate that in the female monkey, the open loop activity of the GnRH pulse generator during juvenile development is only partially

  5. Repeated severe neonatal hemolysis due to Rhesus isoimmunization in a pregnant woman.

    Science.gov (United States)

    Chen, Da-Chung; Chang, Yeing-Kuan; Chen, Wei-Hwa; Liu, Jah-Yao

    2002-05-01

    Rhesus (Rh) isoimmunization presenting as severe neonatal hemolytic disease is rare in RhD negative primigravidas of Chinese ethnicity. We report the case of a 32-year-old pregnant Taiwanese woman, RhD negative, who gave birth vaginally to two RhD-positive full-term fetuses 6 years apart. Antenatal follow-up was uneventful and there was no obvious fetal-maternal hemorrhage except at the performance of amniocentesis at the 19th week of the first pregnancy without anti-D immune globulin prophylaxis. Although anti-D immune globulins were administered to the mother within 1 hour after each birth, both of the newborns had severe neonatal hemolysis refractory to phototherapy and were rescued by exchange transfusions. Both of the children were well at age 7-years-old and one-year-old respectively In conclusion, with suspicion of fetal-maternal hemorrhage in RhD-negative pregnancies post amniocentesis, serial monitoring of indirect Coombs titer with appropriate management is mandatory.

  6. Possible modulation of N-methyl-D,L-aspartic acid induced prolactin release by testicular steroids in the adult male rhesus monkey

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    Arslan, M.; Rizvi, S.S.R.; Jahan, S.; Zaidi, P.; Shahab, M. (Quaid-i-Azam Univ., Islamabad (Pakistan))

    1991-01-01

    N-methyl-D,L-aspartic acid (NMA), an agonist of the neurotransmitter glutamate has been shown to acutely stimulate the release of prolactin (PRL) in intact rats and monkeys. To further investigate the role of neuroexcitatory amino acids in PRL secretion, the effects of NMA administration were examined on PRL release in long term orchidectomized adult rhesus monkeys, in both the absence and presence of testosterone. Intact and long term castrated adult male monkeys weighing between 8-13 kg, were implanted with a catheter via the saphenous vein for blood withdrawal and drug infusion. Blood samples were collected at 10 min intervals for 50 min before and 70 min after administration of the drug or vehicle. Plasma PRL concentrations were estimated using radioimmunoassay. Whereas a single iv injection of NMA induced a prompt discharge of PRL in intact monkeys, an identical dose had surprisingly no effect on PRL secretion in orchidectomized animals. On the other hand, plasma PRL increases in response to a challenge dose of thyrotropin releasing hormone were similar in magnitude in the two groups of monkeys. Testosterone replacement in orchidectomized animals by parenteral administration of testosterone enanthate reinitiated the PRL responsiveness to acute NMA stimulation. These results indicate that N-methyl-D-aspartic acid (NMDA) dependent drive to PRL release in the adult male rhesus monkey may be overtly influenced by the sex steroid milieu.

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

    Science.gov (United States)

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

    2011-05-01

    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.

  8. 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.

  9. 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.

  10. Effects of amphetamine, morphine, and CP 55, 940 on Go/No-Go task performance in rhesus monkeys.

    Science.gov (United States)

    Koek, Wouter; Gerak, Lisa R; France, Charles P

    2015-08-01

    In humans, impulsivity measured as false alarms in a Go/No-Go task is reportedly decreased by amphetamine and is not affected by oxycodone and delta(9)-tetrahydrocannabinol. To model these findings in animals, three rhesus monkeys were trained to perform a food-reinforced Go/No-Go task. In this task, amphetamine was found to decrease false alarms (i.e. responding during No-Go trials), but only at doses that also decreased hits (i.e. responding during Go trials). Morphine generally decreased hits but not false alarms. The cannabinoid receptor agonist CP 55, 940 decreased both false alarms and hits, but only at doses that also decreased the number of trials completed. Additional studies in animals and humans are necessary to delineate the conditions under which amphetamine and other psychoactive drugs affect impulsivity in Go/No-Go tasks.

  11. Simulation modeling of the tissue disposition of formaldehyde to predict nasal DNA-protein cross-links in Fischer 344 rats, rhesus monkeys, and humans.

    Science.gov (United States)

    Conolly, R B; Lilly, P D; Kimbell, J S

    2000-10-01

    Formaldehyde inhalation causes formation of DNA-protein cross-links (DPX) in the nasal mucosa of Fischer 344 (F344) rats and rhesus monkeys. DPX are considered to be part of the mechanism by which cytotoxic and carcinogenic effects of formaldehyde in laboratory animals are exerted, and DPX data have been used as a measure of tissue dose in cancer risk assessments for formaldehyde. Accurate prediction of DPX concentrations in humans is therefore desirable. The goal of this work was to increase confidence in the prediction of human DPX by refining earlier models of formaldehyde disposition and DPX kinetics in the nasal mucosa. Anatomically accurate, computational fluid dynamics models of the nasal airways of F344 rats, rhesus monkeys, and humans were used to predict the regional flux of formaldehyde to the respiratory and olfactory mucosa. A previously developed model of the tissue disposition of formaldehyde and of DPX kinetics was implemented in the graphical simulation tool SIMULINK and linked to the regional flux predictions. Statistical optimization was used to identify parameter values, and good simulations of the data were obtained. The parameter estimates for rats and monkeys were used to guide allometric scale-up to the human case. The relative levels of nasal mucosal DPX in rats, rhesus monkeys, and humans for a given inhaled concentration of formaldehyde were predicted by the model to vary with concentration. This modeling approach reduces uncertainty in the prediction of human nasal mucosal DPX resulting from formaldehyde inhalation.

  12. SURGICAL INTERVENTION AND ACCOMMODATIVE RESPONSES: I. CENTRIPETAL CILIARY BODY, CAPSULE AND LENS MOVEMENT IN RHESUS MONKEYS OF VARYING AGE

    Science.gov (United States)

    Croft, Mary Ann; Mcdonald, Jared P.; James, Rebecca J.; Heatley, Gregg A.; Lin, Ting-Li; Lütjen-Drecoll, Elke; Kaufman, Paul L.

    2009-01-01

    Purpose To determine how surgically altering the normal relationship between the lens and the ciliary body in rhesus monkeys affects centripetal ciliary body and lens movement. Methods In 18 rhesus monkey eyes (aged 6–27 years), accommodation was induced before and after surgery by electrical stimulation of the Edinger-Westphal (E–W) nucleus. Accommodative amplitude was measured by coincidence refractometry. Goniovideography was performed before and after intra- and extra-capsular lens extraction (ICLE, ECLE) and anterior regional zonulolysis. Centripetal lens/capsule movements, centripetal ciliary process (CP) movements, and circumlental space were measured by computerized image analysis of the goniovideography images. Results Centripetal accommodative CP and capsule movement increased in velocity and amplitude post-ECLE compared to pre-ECLE regardless of age (n=5). The presence of the lens substance retarded capsule movement by ~21% in the young eyes and by ~62% in the older eyes. Post-ICLE compared to pre-ICLE centripetal accommodative CP movement was dampened in all eyes in which the anterior vitreous was disturbed (n=7), but not in eyes in which the anterior vitreous was left intact (n=2). Following anterior regional zonulolysis (n=4), lens position shifted toward the lysed quadrant during accommodation. Conclusions The presence of the lens substance, capsule zonular attachments, and Wiegers ligament may play a role in centripetal CP movement. The capsule is still capable of centripetal movement in the older eye (although at a reduced capacity) and may have the ability to produce ~6 diopters of accommodation in the presence of a normal young crystalline lens or a similar surrogate. PMID:18552393

  13. Effects of 14-day treatment with the schedule III anorectic phendimetrazine on choice between cocaine and food in rhesus monkeys.

    Science.gov (United States)

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

    2013-08-01

    The clinical utility of monoamine releasers such as phenmetrazine or d-amphetamine as candidate agonist medications for cocaine dependence is hindered by their high abuse liability. Phendimetrazine is a clinically available schedule III anorectic that functions as a prodrug for phenmetrazine and thus may have lower abuse liability. This study determined the effects of continuous 14-day treatment with phendimetrazine on cocaine vs. food choice in rhesus monkeys (N=4). Responding was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and cocaine injections (0-0.1mg/kg/injection, fixed-ratio 10 schedule). Cocaine choice dose-effect curves were determined daily before and during 14-day periods of continuous intravenous treatment with saline or (+)-phendimetrazine (0.32-1.0mg/kg/h). Effects of 14-day treatment with (+)-phenmetrazine (0.1-0.32 mg/kg/h; N=5) and d-amphetamine (0.032-0.1mg/kg/h; N=6) were also examined for comparison. During saline treatment, food was primarily chosen during availability of low cocaine doses (0, 0.0032, and 0.01 mg/kg/injection), and cocaine was primarily chosen during availability of higher cocaine doses (0.032 and 0.1mg/kg/injection). Phendimetrazine initially decreased overall responding without significantly altering cocaine choice. Over the course of 14 days, tolerance developed to rate decreasing effects, and phendimetrazine dose-dependently decreased cocaine choice (significant at 0.032 mg/kg/injection cocaine). Phenmetrazine and d-amphetamine produced qualitatively similar effects. These results demonstrate that phendimetrazine can produce significant, though modest, reductions in cocaine choice in rhesus monkeys. Phendimetrazine may be especially suitable as a candidate medication for human studies because of its schedule III clinical availability. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Effects of continuous nicotine treatment and subsequent termination on cocaine versus food choice in male rhesus monkeys.

    Science.gov (United States)

    Schwienteck, Kathryn L; Negus, S Stevens; Poklis, Justin L; Banks, Matthew L

    2015-10-01

    One complicating factor in cocaine addiction may be concurrent exposure and potential dependence on nicotine. The aim of the present study was to determine the effects of continuous nicotine treatment and subsequent termination on cocaine versus food choice in rhesus monkeys (Macaca mulatta). For comparison, we also determined effects of the nicotinic receptor antagonist mecamylamine on cocaine versus food choice during continuous saline and nicotine treatment. Rhesus monkeys (N = 3) responded under a concurrent schedule of food pellet (1 g) and intravenous cocaine (0-0.1 mg/kg/injection) availability. Saline and ascending nicotine doses (0.1-1.0 mg/kg/hr, intravenous) were continuously infused for 7-day treatment periods and separated by 24-hr saline treatment periods. Acute effects of mecamylamine (0.32-1.8 mg/kg, intramuscular, 15 min pretreatment) were determined during continuous saline and 0.32-mg/kg/hr nicotine treatments. During saline treatment, cocaine maintained a dose-dependent increase in cocaine choice. Nicotine treatment did not alter cocaine versus food choice. In contrast, preference of 0.032 mg/kg/injection cocaine was attenuated 24 hr following termination of 0.32-mg/kg/hr nicotine treatment, despite no somatic abstinence signs being observed. Acute mecamylamine enhanced cocaine choice during saline treatment and mainly suppressed rates of behavior during nicotine treatment. Overall, continuous nicotine exposure, up to 1 mg/kg/hr, does not enhance cocaine choice and does not produce nicotine dependence, as demonstrated by the lack of abstinence signs. (c) 2015 APA, all rights reserved).

  15. The association of depressed angiogenic factors with reduced capillary density in the Rhesus monkey model of myocardial ischemia.

    Science.gov (United States)

    Zhang, Wenjing; Zhao, Xinmei; Xiao, Ying; Chen, Jianmin; Han, Pengfei; Zhang, Jingyao; Fu, Haiying; James Kang, Y

    2016-07-13

    Depressed capillary density is associated with myocardial ischemic infarction, in which hypoxia-inducible factor 1α (HIF-1α) is increased. The present study was undertaken to examine changes in the angiogenic factors whose expression is regulated by HIF-1 and their relation to the depressed capillary density in the Rhesus monkey model of myocardial ischemic infarction. Male Rhesus monkeys 2-3 years old were subjected to myocardial ischemia by permanent ligation of left anterior descending (LAD) artery leading to the development of myocardial infarction. Eight weeks after LAD ligation, copper concentrations, myocardial histological changes and capillary density were examined, along with Western blot and immunohistochemical analysis of angiogenic factors and detection of HIF-1 activity. Capillary density was significantly decreased but the concentrations of HIF-1α and HIF-1β were significantly increased in the infarct area. However, the levels of mRNA and protein for VEGF and VEGFR1 were significantly decreased. Other HIF-1 regulated angiogenic factors, including Tie-2, Ang-1 and FGF-1, were also significantly depressed, but vascular destabilizing factor Ang-2 was significantly increased. Copper concentrations were depressed in the infarct area. Copper-independent HIF-1 activity was increased shown by the elevated mRNA level of IGF-2, a HIF-1 target gene. Removal of copper by a copper chelator, tetraethylenepentamine, from primary cultures of neonatal rat cardiomyocytes also suppressed the expression of HIF-1 regulated VEGF and BNIP3, but not IGF-2. The data suggest that under ischemic conditions, copper loss suppressed the expression of critical angiogenic genes regulated by HIF-1, but did not affect copper-independent HIF-1 activation of gene expression. This copper-dependent dysregulation of angiogenic gene expression would contribute to the pathogenesis of myocardial ischemic infarction.

  16. Evaluation of the differences of myocardial fibers between acute and chronic myocardial infarction: Application of diffusion tensor magnetic resonance imaging INA Rhesus monkey model

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yu Qing; Cai, Wei; Wang, Lei; Xia, Rui; Chen, Wei; Zheng, Jie [Dept. of Radiology, West China Hospital, Sichuan University, Sichuan (China); Gao, Fabao [Mallinckrodt Institute of Radiology, School of Medicine, Washington University, St. Louis (United States)

    2016-09-15

    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. 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). Comparing with acute MI monkeys (FA: 0.59 ± 0.02; ADC: 5.0 ± 0.6 × 10{sup -4} mm{sup 2}/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{sup -4} mm{sup 2}/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°). 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.

  17. 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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuqing [Department of Radiology, West China Hospital, Sichuan University, Sichuan 610041 (China); CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190 (China); Cai, Wei [Department of Radiology, West China Hospital, Sichuan University, Sichuan 610041 (China); Department of Radiology, Beijing Jishuitan Hospital, 4th Clinical Medical College of Peking University, Beijing 100035 (China); Wang, Lei [Department of Radiology, West China Hospital, Sichuan University, Sichuan 610041 (China); Xia, Rui [Department of Radiology, West China Hospital, Sichuan University, Sichuan 610041 (China); Department of Radiology, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016 (China); Chen, Wei [Department of Radiology, West China Hospital, Sichuan University, Sichuan 610041 (China); Department of Radiology, The First Affiliated Hospital of Kunming Medical University, Yunnan 650032 (China); Zheng, Jie [Mallinckrodt Institute of Radiology, School of Medicine, Washington University, St. Louis, MO 63110 (United States); Gao, Fabao [Department of Radiology, West China Hospital, Sichuan University, Sichuan 610041 (China)

    2016-11-01

    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. 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). Comparing with acute MI monkeys (FA: 0.59 ± 0.02; ADC: 5.0 ± 0.6 × 10{sup -4} mm{sup 2}/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{sup -4}mm{sup 2}/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°). 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.

  18. Rhesus monkeys (Macaca mulatta) adaptively adjust information seeking in response to information accumulated.

    Science.gov (United States)

    Tu, Hsiao-Wei; Pani, Alex A; Hampton, Robert R

    2015-11-01

    Metacognition consists of monitoring and control processes. Monitoring has been inferred when nonhumans use a "decline test" response to selectively escape difficult test trials. Cognitive control has been inferred from selective information-seeking behavior by nonhumans ignorant of needed knowledge. Here we describe a computerized paradigm that extends previous work and assesses dynamic interactions between monitoring and control. Monkeys classified images as containing birds, fish, flowers, or people. To-be-classified images were initially masked, and monkeys were trained to gradually reveal the images by touching a "reveal button." Monkeys could choose to classify images at any time or to reveal more of the images. Thus, they had the opportunity to assess when enough of an image had been revealed to support accurate classification. In Experiment 1, monkeys made more reveal responses before classifying when smaller amounts of the image were revealed by each button touch. In Experiment 2, to-be-classified images were shrunk and covered by 1 critical blocker among other blockers that did not provide information when removed. Monkeys made more reveal responses as the critical blocker was removed later in the trial. In Experiment 3, monkeys were presented with previously classified images with either more or fewer blockers obscuring the image than was the case when they chose to classify that image previously. Monkeys made more reveal responses when information was insufficient than when it was excessive. These results indicate that monkeys dynamically monitor evolving decision processes and adaptively collect information as necessary to maintain accuracy.

  19. 实验猕猴全身CT影像学观察%Observation of whole body CT tomography of the laboratorial rhesus monkey

    Institute of Scientific and Technical Information of China (English)

    范春梅; 李志雄; 周建华

    2012-01-01

    Purpose To research the clinical diagnosis of disease in rhesus monkey with the observation of whole CT tomography of the healthy adult laboratorial monkey, to establish the maps of CT tomography of the healthy adult rhesus monkey, to provide ?the basic image?data of CT technology in the applications of anatomy, clinical diagnosis and scientific experiments of rhesus monkey. Methods (1) 10 laboratorial monkeys were selected for whole body CT tomography. (2)After general anesthesia, the monkeys were placed in supine position and the volume data were collected to obtain the whole body CT images of normal rhesus monkey by using plain and enhanced scanning technology. (3)The scan obtained volume data were restructured into 2D or 3D images using CT image post- processing technology. Results (1)the Continuous CT tomography data set of living rhesus monkey were obtained. (2)From the CT tomography images, anatomical images were carefully selected and edited to establish the CT tomography map of ?laboratorial rhesus monkeys. There are 4 representative CT tomography images and 5 3D restructured images in this paper. (3)Describes the rhesus monkey's physiological structural characteristics and the difference between rhesus monkey and human. Conclusion (1)CT tomography image can clearly display and distinguish the rhesus monkey's structure of tissues and organs. (2)The fundamental imaging data obtained in the test provide a reference of CT tomography technology in the field of rhesus monkey anatomy research, clinical diagnosis of disease and scientific experiments. (3)Some preliminary results of rhesus monkey CT tomography imaging were seen in this paper, further study will be done in the field of selection of parameters of rhesus monkey CT tomography technology and establishing of quantitative statistics data of rhesus monkey organs and tissues.%目的:应用CT技术对成年实验猕猴全身进行断层扫描,探讨CT技术

  20. Kinetic analysis of interactions of paraoxon and oximes with human, Rhesus monkey, swine, rabbit, rat and guinea pig acetylcholinesterase.

    Science.gov (United States)

    Worek, Franz; Aurbek, Nadine; Wille, Timo; Eyer, Peter; Thiermann, Horst

    2011-01-15

    Previous in vitro studies showed marked species differences in the reactivating efficiency of oximes between human and animal acetylcholinesterase (AChE) inhibited by organophosphorus (OP) nerve agents. These findings provoked the present in vitro study which was designed to determine the inhibition, aging, spontaneous and oxime-induced reactivation kinetics of the pesticide paraoxon, serving as a model compound for diethyl-OP, and the oximes obidoxime, pralidoxime, HI 6 and MMB-4 with human, Rhesus monkey, swine, rabbit, rat and guinea pig erythrocyte AChE. Comparable results were obtained with human and monkey AChE. Differences between human, swine, rabbit, rat and guinea pig AChE were determined for the inhibition and reactivation kinetics. A six-fold difference of the inhibitory potency of paraoxon with human and guinea pig AChE was recorded while only moderate differences of the reactivation constants between human and animal AChE were determined. Obidoxime was by far the most effective reactivator with all tested species. Only minor species differences were found for the aging and spontaneous reactivation kinetics. The results of the present study underline the necessity to determine the inhibition, aging and reactivation kinetics in vitro as a basis for the development of meaningful therapeutic animal models, for the proper assessment of in vivo animal data and for the extrapolation of animal data to humans.

  1. 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.

  2. Immunisation of rhesus monkeys with Streptococcus mutans, Lactobacillus acidophilus and lipoteichoic acid for protection against dental caries.

    Science.gov (United States)

    Caldwell, J; Lehner, T

    1982-08-01

    An attempt was made to protect rhesus monkeys from dental caries by immunisation with Streptococcus mutans, Lactobacillus acidophilus and lipoteichoic acid (LTA). The vaccine composed of S. mutans gave significant protection against caries, a decrease in the number of S. mutans, an increase in IgG antibodies and a moderate increase in complement-fixing antibodies to LTA. When LTA was used as immunogen, there was only a small reduction in caries, without any detectable antibodies to LTA and a slight increase in IgG antibodies to cell of S. mutans. Vaccines of L. acidophilus or L. fermentum gave no protection. A combined vaccine of S. mutans and L. acidophilus did not reduce the incidence of caries but the antibody titre to cells of S. mutans was raised to a level comparable with that in the S. mutans-immunised monkeys. The results of this investigation in a subhuman primate confirm that immunisation with S. mutans induces protection against caries, unlike the attempt to immunise with two selected strains of lactobacilli. More studies are required to establish the role of specific serotypes of lactobacilli in the development of dental caries.

  3. Excitatory amino acid changes in the brains of rhesus monkeys following selective cerebral deep hypothermia and blood flow occlusion

    Institute of Scientific and Technical Information of China (English)

    Jun Pu; Xiaoqun Niu; Jizong Zhao

    2013-01-01

    Selective cerebral deep hypothermia and blood flow occlusion can enhance brain tolerance to ischemia and hypoxia and reduce cardiopulmonary complications in monkeys. Excitotoxicity induced by the release of a large amount of excitatory amino acids after cerebral ischemia is the major mechanism underlying ischemic brain injury and nerve cell death. In the present study, we used selective cerebral deep hypothermia and blood flow occlusion to block the bilateral common carotid arteries and/or bilateral vertebral arteries in rhesus monkey, followed by reperfusion using Ringer's solution at 4°C. Microdialysis and transmission electron microscope results showed that selective cerebral deep hypothermia and blood flow occlusion inhibited the release of glutamic acid into the extracellular fluid in the brain frontal lobe and relieved pathological injury in terms of the ultrastructure of brain tissues after severe cerebral ischemia. These findings indicate that cerebral deep hypothermia and blood flow occlusion can inhibit cytotoxic effects and attenuate ischemic/ hypoxic brain injury through decreasing the release of excitatory amino acids, such as glutamic acid.

  4. Comparison of the effects of methamphetamine, bupropion, and methylphenidate on the self-administration of methamphetamine by rhesus monkeys.

    Science.gov (United States)

    Schindler, Charles W; Gilman, Joanne P; Panlilio, Leigh V; McCann, David J; Goldberg, Steven R

    2011-02-01

    The effectiveness of methadone as a treatment for opioid abuse and nicotine preparations as treatments for tobacco smoking has led to an interest in developing a similar strategy for treating psychostimulant abuse. The current study investigated the effects of three such potential therapies on intravenous methamphetamine self-administration (1 - 30 μg/kg/injection) in rhesus monkeys. When given as a presession intramuscular injection, a high dose of methamphetamine (1.0 mg/kg) decreased intravenous methamphetamine self-administration but did not affect responding for a food reinforcer during the same sessions. However, the dose of intramuscular methamphetamine required to reduce intravenous methamphetamine self-administration exceeded the cumulative amount taken during a typical self-administration session, and pretreatment with a low dose of methamphetamine (0.3 mg/kg) actually increased self-administration in some monkeys at the lower self-administration dose. Like pretreatment with methamphetamine, pretreatment with bupropion (3.2 mg/kg) decreased methamphetamine self-administration but did not affect responding for food. Pretreatment with methylphenidate (0.56 mg/kg) did not significantly alter methamphetamine self-administration. These results suggest that some agonist-like agents can decrease methamphetamine self-administration. Although the most robust effects occurred with a high dose of methamphetamine, safety and abuse liability considerations suggest that bupropion should also be considered for further evaluation as a methamphetamine addiction treatment.

  5. Swine Influenza Virus Vaccine: Potentiation of Antibody Responses in Rhesus Monkeys

    Science.gov (United States)

    1977-04-01

    and of polyllUCI. Monkeys given the vac- Fever was not observed in monkeys carboxymethylcellulose lpoly(ICL.C)l cine-adjuvant combinations were gisen...1ICL0 - - ~ - __C D unit antigen prepared from the AINJ/76 k 0 7142425lO (New Jersey; swine) strain of virus. when ug) 0 7- 142Q10 5 tested in monkeys...7) (12) (34) (M0) (40) prepared as described previously (3). 100 < < 20 40 160 80 20 was 10or .00 Ag/kg in the first study 100 < ម 40 320 320 64

  6. 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

  7. Correlation between the concentration of serum polychlorinated biphenyls (PCBs) in pregnant cynomolgus monkeys and their offspring's behavioral scores in eye-contact test and finger maze learning test

    Energy Technology Data Exchange (ETDEWEB)

    Negishi, T. [Aoyama Gakuin Univ., Kanagawa (Japan); Takasuga, T. [Shimadzu Techno-Research Inc., Kyoto (Japan); Kawasaki, K. [Hoshi Univ., Tokyo (Japan); Kuroda, Y. [CREST Japan Science and Technology Corp., Saitama (Japan); Yoshikawa, Y. [The Univ. of Tokyo (Japan)

    2004-09-15

    A recent review suggested that pre- or perinatal exposure of developing fetuses to dioxins, the widespread environmental contaminants, such as polychrorinated biphenlys (PCBs), induce the irreversible abnormalities in the functions of central nervous system (CNS) in human. These chemicals can be transferred to each fetus and naonate transplacentally and lactationally in rhesus monkey. Several studies also reported the adverse effect of PCB on CNS development in rodents and monkeys as well as on behavior in rodents and monkeys. In the present study, we show a preliminary data about the correlation between the serum concentrations of PCBs in pregnant cynomolgus monkeys (Macaca fascicularis) and the scores of two behavioral tests, eye-contact test and four-step finger maze test, which evaluate consciousness against human observer and learning ability, respectively, in their offspring. This experimental surveillance system using non-human primates would be useful to predict the risk of PCBs exposure in human fetuses because of the similarities of cynomolgus monkey to human with regard to reproduction, developmental parameter, and others.

  8. 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

  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. Cognitive mechanisms for transitive inference performance in rhesus monkeys: measuring the influence of associative strength and inferred order.

    Science.gov (United States)

    Gazes, Regina Paxton; Chee, Nicholas W; Hampton, Robert R

    2012-10-01

    If Ben is taller than Emily and Emily is taller than Dina, one can infer that Ben is taller than Dina. This process of inferring relations between stimuli based on shared relations with other stimuli is called transitive inference (TI). Many species solve TI tasks in which they learn pairs of overlapping stimulus discriminations (A+B-, B+C-, etc.) and are tested with non-adjacent novel test pairings (BD). When relations between stimuli are determined by reinforcement (A is reinforced when paired with B, B when paired with C), performance can be controlled by the associative values of individual stimuli or by logical inference. In Experiment 1 rhesus monkeys (Macaca mulatta) chose the higher ranked item on non-adjacent test trials after training on a 7-image TI task. In Experiment 2 we measured the associative values of 7 TI images and found that these values did not correlate with choice in TI tests. In Experiment 3 large experimental manipulations of the associative value of images did influence performance in some TI test pairings, but performance on other pairs was consistent with the implied order. In Experiment 4 monkeys linked two previously learned 7-item lists into one 14-item list after training with a single linking pair. Linking cannot be explained by associative values. Associative value can control choice in TI tests in at least some extreme circumstances. Implied order better explains most TI choices in monkeys, and is a more viable mechanism for TI of social dominance, which has been observed in birds and fish.

  11. 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.

  12. 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

  13. Treatment and risk factor analysis of hypoglycemia in diabetic rhesus monkeys.

    Science.gov (United States)

    He, Sirong; Chen, Younan; Wei, Lingling; Jin, Xi; Zeng, Li; Ren, Yan; Zhang, Jie; Wang, Li; Li, Hongxia; Lu, Yanrong; Cheng, Jingqiu

    2011-02-01

    In order to anticipate and promptly treat hypoglycemia in diabetic monkeys treated with insulin or other glucose-lowering drugs, the relationships between the incidence and symptoms of hypoglycemia in these animals, and many factors involved in model development and sustainment were analyzed. Different procedures were performed on 22 monkeys for the induction of diabetes. The monkey models were evaluated by blood glucose, insulin, C-peptide levels and intravenous glucose tolerance tests. A glucose treatment program for the diabetic monkeys was administered and laboratory tests were regularly performed. A standard procedure of hypoglycemia treatment was established and the risk factors of hypoglycemia were analyzed by a logistic regression model. Furthermore, the relationships between the four methods of diabetes induction, renal function, glycemic control and hypoglycemia were studied using one-way analysis of variance and t-test. We found that the hypoglycemic conditions of diabetic monkeys were improved rapidly by our treatment. The statistical analysis suggested that the modeling methods, renal function and glycemic control were related to the incidence of hypoglycemia. In detail, the progress of diabetes, effects of glycemic control and, particularly, the severity of the hypoglycemia differed according to the induction strategy used. The models induced by partial pancreatectomy with low-dose streptozotocin were not prone to hypoglycemia and their glycemic controls were stable. However, the models induced by total pancreatectomy were more vulnerable to severe hypoglycemia and their glycemic controls were the most unstable. Moreover, the levels of blood creatinine and triglyceride increased after the development of diabetes, which was related to the occurrence of hypoglycemia. In conclusion, we suggested that total pancreatectomy and renal impairment are two important risk factors for hypoglycemia in diabetic monkeys. More attention should be paid to daily care

  14. Effect of Ionizing Radiation on Prostaglandins and Gastric Secretion in Rhesus Monkeys

    Science.gov (United States)

    1985-01-01

    gastric electrical control activity when gastric serosal electrodes are used in conjunction with skin electrodes (16,17). Each tracing was examined blindly...damage to gastric mucosal cells, to the myenteric plexus, or the smooth muscle similar to the one observed during the late postirradiation period (5). In...F: ---------- EFFECT OF IONIZING RADIATION ON PROSTAGLANDINS AND GASTRIC SECRETION IN RHESUS MONKS Andre Dubois Etienne Danquechin Dorval Linda Steel

  15. Functional disruption of the dystrophin gene in rhesus monkey using CRISPR/Cas9.

    Science.gov (United States)

    Chen, Yongchang; Zheng, Yinghui; Kang, Yu; Yang, Weili; Niu, Yuyu; Guo, Xiangyu; Tu, Zhuchi; Si, Chenyang; Wang, Hong; Xing, Ruxiao; Pu, Xiuqiong; Yang, Shang-Hsun; Li, Shihua; Ji, Weizhi; Li, Xiao-Jiang

    2015-07-01

    CRISPR/Cas9 has been used to genetically modify genomes in a variety of species, including non-human primates. Unfortunately, this new technology does cause mosaic mutations, and we do not yet know whether such mutations can functionally disrupt the targeted gene or cause the pathology seen in human disease. Addressing these issues is necessary if we are to generate large animal models of human diseases using CRISPR/Cas9. Here we used CRISPR/Cas9 to target the monkey dystrophin gene to create mutations that lead to Duchenne muscular dystrophy (DMD), a recessive X-linked form of muscular dystrophy. Examination of the relative targeting rate revealed that Crispr/Cas9 targeting could lead to mosaic mutations in up to 87% of the dystrophin alleles in monkey muscle. Moreover, CRISPR/Cas9 induced mutations in both male and female monkeys, with the markedly depleted dystrophin and muscle degeneration seen in early DMD. Our findings indicate that CRISPR/Cas9 can efficiently generate monkey models of human diseases, regardless of inheritance patterns. The presence of degenerated muscle cells in newborn Cas9-targeted monkeys suggests that therapeutic interventions at the early disease stage may be effective at alleviating the myopathy.

  16. Uncertain responses by humans and rhesus monkeys (Macaca mulatta) in a psychophysical same-different task

    Science.gov (United States)

    Shields, W. E.; Smith, J. D.; Washburn, D. A.; Rumbaugh, D. M. (Principal Investigator)

    1997-01-01

    The authors asked whether animals, like humans, use an uncertain response adaptively to escape indeterminate stimulus relations. Humans and monkeys were placed in a same-different task, known to be challenging for animals. Its difficulty was increased further by reducing the size of the stimulus differences, thereby making many same and different trials difficult to tell apart. Monkeys do escape selectively from these threshold trials, even while coping with 7 absolute stimulus levels concurrently. Monkeys even adjust their response strategies on short time scales according to the local task conditions. Signal-detection and optimality analyses confirm the similarity of humans' and animals' performances. Whereas associative interpretations account poorly for these results, an intuitive uncertainty construct does so easily. The authors discuss the cognitive processes that allow uncertainty's adaptive use and recommend further comparative studies of metacognition.

  17. Efficacy and the discriminative stimulus effects of negative GABAA modulators, or inverse agonists, in diazepam-treated rhesus monkeys.

    Science.gov (United States)

    McMahon, Lance R; Gerak, Lisa R; France, Charles P

    2006-08-01

    In benzodiazepine (BZ)-dependent animals, the effects of negative GABA(A) modulators at BZ sites are not clearly related to differences in negative efficacy (i.e., inverse agonist activity). A flumazenil discriminative stimulus in diazepam (5.6 mg/kg/day)-treated rhesus monkeys was used to test the hypothesis that the effects of negative GABA(A) modulators at BZ sites do not vary as a function of efficacy in BZ-dependent animals. Negative GABA(A) modulators varying in efficacy were studied in combination with positive modulators acting at different modulatory sites (BZ, barbiturate, and neuroactive steroid sites). The negative modulators Ro 15-4513 (ethyl 8-azido-6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-alpha]-[1,4]benzodiazepine-3-carboxylate) and ethyl beta-carboline-3-carboxylate (beta-CCE) substituted for the flumazenil discriminative stimulus. Acute pretreatment with diazepam (3.2 and 10 mg/kg s.c., in addition to 5.6 mg/kg/day p.o.), pentobarbital (3.2 and 10 mg/kg), or pregnanolone (1 and 3.2 mg/kg) attenuated the flumazenil discriminative stimulus and also attenuated the flumazenil-like discriminative stimulus effects of Ro 15-4513 and beta-CCE. Attenuation of the discriminative stimulus effects of flumazenil, Ro 15-4513, and beta-CCE did not systematically vary as a function of negative efficacy. Compared with their discriminative stimulus effects in untreated monkeys discriminating midazolam, both pregnanolone and pentobarbital were relatively more potent than diazepam in attenuating the discriminative stimulus effects of flumazenil, Ro 15-4513, and beta-CCE in diazepam-treated monkeys. These results show that the discriminative stimulus effects of BZ-site neutral and negative modulators are not different in BZ-dependent animals trained to discriminate flumazenil, and extend the results of a previous study showing that positive modulators acting at non-BZ sites are especially potent in attenuating the effects of flumazenil in diazepam-treated monkeys (i

  18. 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

    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......, 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 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...

  19. Selection and Pairing of ’Normal’ Rhesus Monkeys (Macaca mulatta) for Research.

    Science.gov (United States)

    1978-11-08

    ECG Blood Pressure ___Ocular Motility ___Pupillary Reflexes (Direct and Indirect) Fascial Muscle Tone ___Apply Mydriatic Agents to Dilate Eyes Head...selectees would be subjected to frequent handling and manipulation . The radiographs of seven other monkeys contained evidence of abdominal opacities

  20. Effects of chair restraint on the strength of the tibia in rhesus monkeys

    Science.gov (United States)

    Hutchinson, T. M.; Bakulin, A. V.; Rakhmanov, A. S.; Martin, R. B.; Steele, C. R.; Arnaud, S. B.

    2001-01-01

    To determine the effects of the relative inactivity and unloading on the strength of the tibias of monkeys, Macaca mulatta, we used a non-invasive test to measure bending stiffness, or EI (Nm2), a mechanical property. The technique was validated by comparisons of in vivo measurements with standard measures of EI in the same bones post-mortem (r2 = 0.95, P monkeys, 3.0+/-0.7 years and 3.6+/-0.6 kg, revealed EI to be 16% higher in the right than left tibia (4.4+/-1.6 vs. 3.7+/-1.6 Nm2, P monkeys, restrained in chairs for 14 days, showed decreases in EI. There were no changes in EI in two chaired monkeys that lost weight during a 2-week space flight. The factors that account for both the decreases in bone mechanical properties after chair restraint at 1 g and lack of change after microgravity remain to be identified. Metabolic factors associated with body weight changes are suggested by our results.

  1. Dissociation of Active Working Memory and Passive Recognition in Rhesus Monkeys

    Science.gov (United States)

    Basile, Benjamin M.; Hampton, Robert R.

    2013-01-01

    Active cognitive control of working memory is central in most human memory models, but behavioral evidence for such control in nonhuman primates is absent and neurophysiological evidence, while suggestive, is indirect. We present behavioral evidence that monkey memory for familiar images is under active cognitive control. Concurrent cognitive…

  2. Dissociation of Active Working Memory and Passive Recognition in Rhesus Monkeys

    Science.gov (United States)

    Basile, Benjamin M.; Hampton, Robert R.

    2013-01-01

    Active cognitive control of working memory is central in most human memory models, but behavioral evidence for such control in nonhuman primates is absent and neurophysiological evidence, while suggestive, is indirect. We present behavioral evidence that monkey memory for familiar images is under active cognitive control. Concurrent cognitive…

  3. The effective connectivity of the seizure onset zone and ictal perfusion changes in amygdala kindled rhesus monkeys.

    Science.gov (United States)

    Cleeren, Evy; Premereur, Elsie; Casteels, Cindy; Goffin, Karolien; Janssen, Peter; Van Paesschen, Wim

    2016-01-01

    Epileptic seizures are network-level phenomena. Hence, epilepsy may be regarded as a circuit-level disorder that cannot be understood outside this context. Better insight into the effective connectivity of the seizure onset zone and the manner in which seizure activity spreads could lead to specifically-tailored therapies for epilepsy. We applied the electrical amygdala kindling model in two rhesus monkeys until these animals displayed consistent stage IV seizures. At this stage, we investigated the effective connectivity of the amygdala by means of electrical microstimulation during fMRI (EM-fMRI). In addition, we imaged changes in perfusion during a seizure using ictal SPECT perfusion imaging. The spatial overlap between the connectivity network and the ictal perfusion network was assessed both at the regional level, by calculating Dice coefficients using anatomically defined regions of interest, and at the voxel level. The kindled amygdala was extensively connected to bilateral cortical and subcortical structures, which in many cases were connected multisynaptically to the amygdala. At the regional level, the spatial extents of many of these fMRI activations and deactivations corresponded to the respective increases and decreases in perfusion imaged during a stage IV seizure. At the voxel level, however, some regions showed residual seizure-specific activity (not overlapping with the EM-fMRI activations) or fMRI-specific activation (not overlapping with the ictal SPECT activations), indicating that frequently, only a part of a region anatomically connected to the seizure onset zone participated in seizure propagation. Thus, EM-fMRI in the amygdala of electrically-kindled monkeys reveals widespread areas that are often connected multisynaptically to the seizure focus. Seizure activity appears to spread, to a large extent, via these connected areas.

  4. Effects of phendimetrazine treatment on cocaine vs food choice and extended-access cocaine consumption in rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L; Blough, Bruce E; Fennell, Timothy R; Snyder, Rodney W; Negus, S Stevens

    2013-12-01

    There is currently no Food and Drug Administration-approved pharmacotherapy for cocaine addiction. Monoamine releasers such as d-amphetamine constitute one class of candidate medications, but clinical use and acceptance are hindered by their own high-abuse liability. Phendimetrazine (PDM) is a schedule III anorectic agent that functions as both a low-potency monoamine-uptake inhibitor and as a prodrug for the monoamine-releaser phenmetrazine (PM), and it may serve as a clinically available, effective, and safer alternative to d-amphetamine. This study determined efficacy of chronic PDM to reduce cocaine self-administration by rhesus monkeys (N=4) using a novel procedure that featured both daily assessments of cocaine vs food choice (to assess medication efficacy to reallocate behavior away from cocaine choice and toward choice of an alternative reinforcer) and 20 h/day cocaine access (to allow high-cocaine intake). Continuous 21-day treatment with ramping PDM doses (days 1-7: 0.32 mg/kg/h; days 8-21: 1.0 mg/kg/h) reduced cocaine choices, increased food choices, and nearly eliminated extended-access cocaine self-administration without affecting body weight. There was a trend for plasma PDM and PM levels to correlate with efficacy to decrease cocaine choice such that the monkey with the highest plasma PDM and PM levels also demonstrated the greatest reductions in cocaine choice. These results support further consideration of PDM as a candidate anti-cocaine addiction pharmacotherapy. Moreover, PDM may represent a novel pharmacotherapeutic approach for cocaine addiction because it may simultaneously function as both a monoamine-uptake inhibitor (via the parent drug PDM) and as a monoamine releaser (via the active metabolite PM).

  5. Dengue type four viruses with E-Glu345Lys adaptive mutation from MRC-5 cells induce low viremia but elicit potent neutralizing antibodies in rhesus monkeys.

    Science.gov (United States)

    Lin, Hsiao-Han; Lee, Hsiang-Chi; Li, Xiao-Feng; Tsai, Meng-Ju; Hsiao, Hung-Ju; Peng, Jia-Guan; Sue, Shih-Che; Qin, Cheng-Feng; Wu, Suh-Chin

    2014-01-01

    Knowledge of virulence and immunogenicity is important for development of live-attenuated dengue vaccines. We previously reported that an infectious clone-derived dengue type 4 virus (DENV-4) passaged in MRC-5 cells acquired a Glu345Lys (E-E345K) substitution in the E protein domain III (E-DIII). The same cloned DENV-4 was found to yield a single E-Glu327Gly (E-E327G) mutation after passage in FRhL cells and cause the loss of immunogenicity in rhesus monkeys. Here, we used site-directed mutagenesis to generate the E-E345K and E-E327G mutants from DENV-4 and DENV-4Δ30 infectious clones and propagated in Vero or MRC-5 cells. The E-E345K mutations were consistently presented in viruses recovered from MRC-5 cells, but not Vero cells. Recombinant E-DIII proteins of E345K and E327G increased heparin binding correlated with the reduced infectivity by heparin treatment in cell cultures. Different from the E-E327G mutant viruses to lose the immunogencity in rhesus monkeys, the E-E345K mutant viruses were able to induce neutralizing antibodies in rhesus monkeys with an almost a 10-fold lower level of viremia as compared to the wild type virus. Monkeys immunized with the E-E345K mutant virus were completely protected with no detectable viremia after live virus challenges with the wild type DENV-4. These results suggest that the E-E345K mutant virus propagated in MRC-5 cells may have potential for the use in live-attenuated DENV vaccine development.

  6. Cognition in aged rhesus monkeys: effect of DHEA and correlation with steroidogenic gene expression.

    Science.gov (United States)

    Sorwell, K G; Renner, L; Weiss, A R; Neuringer, M; Kohama, S G; Urbanski, H F

    2017-03-01

    Estradiol supplementation has been shown to enhance cognitive performance in old ovariectomized rhesus macaques (Macaca mulatta). To determine if similar benefits could be achieved in perimenopausal animals using alternative hormonal supplements, we administered dehydroepiandrosterone (DHEA) to old ovary-intact female rhesus macaques for ∼2.5 months. Using computerized touch screen memory tasks, including delayed response (DR) and delayed matching-to-sample (DMS), we observed improved performance with time in all of the animals but failed to detect a significant effect of DHEA. On the other hand, gene expression profiling disclosed a significant correlation between cognitive performance and the expression of several steroidogenic and steroid-responsive genes. The DR performance was positively correlated with hippocampal expression of AKR1C3 and STAR and negatively correlated with the expression of SDRD5A1. A positive correlation was also found between DMS performance and prefrontal cortical expression of AKR1C3 and a negative correlation with STAR, as well as a negative correlation with the hippocampal expression of HSD11B1 and NR3C1. Taken together, the results suggest that steroidogenic gene regulation within the brain may help to maintain cognitive function during the perimenopausal transition period, despite a decline in sex-steroid levels in the circulation. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  7. Long-term effects of repeated superovulation on ovarian structure and function in rhesus monkeys.

    Science.gov (United States)

    Dong, Guoying; Guo, Yueshuai; Cao, Huarong; Zhou, Tao; Zhou, Zuomin; Sha, Jiahao; Guo, Xuejiang; Zhu, Hui

    2014-11-01

    To assess the long-term effects of repeated controlled ovarian hyperstimulation (COH) on ovarian structure and function. Experimental study. Laboratory. Adult female rhesus macaques. A repeated COH rhesus macaque model (superovulation group) with spontaneously ovulating macaques used as controls (normal group) and samples of serum and ovarian tissue collected over a 5-year period. Steroid hormone levels, and structural, functional, and protein changes in ovaries. The follicular histology, proportion of follicles at each developmental stage, and expression levels of oocyte-specific genes showed no statistically significant differences between the two groups. However, the superovulation group exhibited mitochondrial abnormalities in the granulosa cells and a low expression of genes involved in steroid hormone synthesis compared with the normal group. A comparison of protein expression in the ovaries of both groups using tandem mass tag labeling with mass spectrometry revealed that most of the differentially-expressed proteins were down-regulated in the superovulation group. These proteins were mainly localized in the mitochondria and cytosol, and changes in protein levels in the superovulation group mainly inhibited cell proliferation and differentiation but promoted apoptosis. Our study indicates that repeated COH could change the expression of many proteins in the ovaries even after several years, potentially affecting the development and function of ovarian cells. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. 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.

  9. 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.

  10. 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.

  11. Do rhesus monkeys (Macaca mulatta) perceive the Zöllner illusion?

    Science.gov (United States)

    Agrillo, Christian; Parrish, Audrey E; Beran, Michael J

    2014-08-01

    A long-standing debate surrounds the issue of whether human and nonhuman animals share the same perceptual mechanisms. In humans, the Zöllner illusion occurs when two parallel lines appear to be convergent when oblique crosshatching lines are superimposed. Although one baboon study suggests that they too might perceive this illusion, the results of that study were unclear, whereas two recent studies suggest that birds see this illusion in the opposite direction from humans. It is currently unclear whether these mixed results are an artifact of the experimental design or reflect a peculiarity of birds' visual system or, instead, a wider phenomenon shared among nonhuman mammals. Here, we trained 6 monkeys to select the narrower of two gaps at the end of two convergent lines. Three different conditions were set up: control (no crosshatches), perpendicular (crosshatches not inducing the illusion), and Zöllner (crosshatches inducing the illusion in humans). During training, the degrees of convergence between the two lines ranged from 15° to 12°. Monkeys that reached the training criterion were tested with more difficult discriminations (11°-1°), including probe trials with parallel lines (0°). The results showed that monkeys perceived the Zöllner illusion in the same direction as humans. Comparison of these data with the data from bird studies points toward the existence of different orientation-tuned mechanisms between primate and nonprimate species.

  12. 实验猕猴头颈部CT影像学观察%Observation of head CT tomography the laboratorial rhesus monkey

    Institute of Scientific and Technical Information of China (English)

    范春梅; 李志雄; 周建华

    2012-01-01

    5 male and 5 female health adult monkeys aged 6-10 years were selected for head CT tomography. After general anesthesia, the monkeys were placed on the table-board of CT in supine position and the volume data were collected. Scanned images of head were obtained by CT tomography.The scan obtained volume data were restructured into 2D or 3D images using CT image post-processing technology. Results The head structure Continuous CT tomography images and restructured images of living rhesus monkey were obtained, From the CT images the structure of tissues and organs of rhesus monkey's head can be clearly displayed and distinguished, such as cervical spine, skull and optic nerve. But the distinction between the cerebral gray matter and white matter and soft tissue are not so well. The basic information of the head CT tomography images of healthy adult rhesus monkey is established, which provides a reference for research of CT imaging of rhesus monkey, research of anatomy, the clinical diagnosis of the disease and the scientific experiments.%选择实验猕猴10只,雌雄各半,年龄6~10岁;全身麻醉后,置于CT诊断床上,取头前尾后仰卧位,采用平扫进行容积数据采集,获取正常猕猴头颈部CT影像图片。利用CT图像后处理技术对扫描获得的容积数据进行2D或3D的图像重组处理获得了实验猕猴头部结构CT连续断层扫描图像和重建图像。CT影像能够较好的显示及分辨猕猴头颈部的组织器官结构,如颈椎、颅骨、视神经等;但对脑的灰、白质的区分和软组织的分辨不够理想。试验获得了正常成年猕猕头颈部的影像学基础资料,为CT技术在猕猴影像学研究、解剖学研究、疾病的临床诊断及科学实验方面的应用,提供了参考。

  13. HEARING LOSS IN THE RHESUS MONKEY AFTER REPEATED EXPOSURES TO IDENTICAL NOISES,

    Science.gov (United States)

    hearing loss in monkeys. Five animals were exposed to repeated single-pulse noises alternately at 72- and 96-hour intervals, to observe intersubject and intra-subject variations in hearing behavior under similar physical-noise conditions. Audiograms were taken periodically, from two minutes after exposure to 72 hours later, for 2 and 4 kc test tones. There were distinctive differences in individual-animal patterns of hearing loss and recovery. Two animals clearly showed smaller hearing losses during the later exposure sessions, and that loss

  14. 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

  15. Immunogenicity in mice and rhesus monkeys vaccinated with recombinant vaccinia virus expressing bivalent E7E6 fusion proteins from human papillomavirus types 16 and 18

    Directory of Open Access Journals (Sweden)

    Tian Houwen

    2011-06-01

    Full Text Available Abstract Background Persistent infection with high-risk human papillomavirus (HPV is a predominant cause of cervical cancer, and HPV16 and HPV18 occur in 50% and 20% of cervical cancer cases, respectively. The viral oncogenes E6 and E7 are constitutively expressed by HPV-associated tumour cells and can therefore be used as target antigens for immunotherapy. In this study, we constructed a recombinant vaccinia virus co-expressing the HPV16/18 E7E6 fusion proteins (rVVJ16/18E7E6 for use as a therapeutic vaccine for the treatment of HPV16+ and HPV18+ cancers. Methods We constructed a bivalent recombinant vaccinia virus expressing modified E7E6 fusion proteins of HPV type 16 and 18 (rVVJ16/18E7E6 based on the vaccinia virus Tiantan strain. We then defined the cellular immune responses to the virus in mice and rhesus monkeys and assessed antitumour efficacy of these responses in mice using the TC-1 tumour challenge model. Results Our data demonstrated that rVVJ16/18E7E6 was able to elicit varying levels of CD8+ T cell immune responses and lysis of target cells in mice in response to peptides HPV16E749-57 and HPV18E667-75. Furthermore, the virus was also able to induce anti-tumour responses in the HPV16+ TC-1 tumour challenge model, including partial protection (30-40% and delayed tumour appearance. In addition, the virus was able to induce immune responses in rhesus monkeys. Conclusions The recombinant vaccinia virus rVVJ16/18E7E6 can generate clear and significant cellular immunity in both mice and rhesus monkeys. These data provide a basis for the use of this recombinant virus as a potential vaccine candidate for further study.

  16. 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.

  17. Specific humoral immune responses in rhesus monkeys vaccinated with the Alzheimer's disease-associated β-amyloid 1-15 peptide vaccine

    Institute of Scientific and Technical Information of China (English)

    LI Shao-bing; WANG Hua-qiao; LIN Xian; XU Jie; XIE Yao; YUAN Qun-fang; YAO Zhi-bin

    2005-01-01

    Background Alzheimer's disease(AD) is a neurodegenerative disorder characterized by overproduction of β-amyloid (Aβ), with the subsequent pathologic deposition of Aβ which is important for memory and cognition. Recent studies showed murine models of AD and AD patients inoculated with Aβ1-42 peptide vaccine had a halted or delayed pathological progression of AD. Unfortunately, the clinical phase Ⅱa trial of Aβ1-42 peptide vaccine (AN1792) was halted prematurely because of episodes of menigoencephalitis in 18 of the vaccinated patients. The vaccination of BALB/c or Tg2576 transgenic mouse with Aβ1-15 peptide vaccine is safe and the immune effects are satisfactory. This study further characterizes the specific humoral immune responses in adult rhesus monkeys induced by Aβ1-15 peptide vaccine.Methods Five male adult rhesus monkeys were injected intramuscularly with Aβ1-15 peptide vaccine at baseline and at weeks 2, 6, 10, 14, 18 and 22. The titers and IgG isotypes of the antibody against Aβ1-42 in serum was measured by Enzyme-linked Immunosorbent Assay (ELISA). The specificity of the antibody against Aβ1-42 was determined by Western blot. The Aβ plaques in Tg2576 transgenic mouse brain were stained with the antiserum using immunohistochemistry method.Results At the eighth week after the vaccination, antibody against Aβ1-42 began to develop significantly in serum. The titers of the antibody increased following vaccine boosted and reached 1∶3840 at the twenty-fourth week, then decreased after the termination of inoculation. The IgG1 was accounted for the highest level in the antiserum pool. The antibody against Aβ1-42 showed high specificity. The Aβ plaques in Tg2576 transgenic mouse brain were labeled with the antiserum.Conclusion Aβ1-15 vaccine can induce vigorously specific humoral immune responses in adult rhesus monkey.

  18. 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.

  19. 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.

  20. No strings attached: Physiological Monitoring of Rhesus Monkeys (Macaca mulatta with Thermal Imaging.

    Directory of Open Access Journals (Sweden)

    Stephanos eIoannou

    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.

  1. 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.

  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.

  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. Effects of feeding fish oil on the properties of lipoproteins isolated from rhesus monkeys consuming an atherogenic diet.

    Science.gov (United States)

    Soltys, P A; Mazzone, T; Wissler, R W; Vahed, S; Rangnekar, V; Lukens, J; Vesselinovitch, D; Getz, G S

    1989-04-01

    This study examined plasma lipids and lipoproteins of rhesus monkeys fed fish oil incorporated into a highly atherogenic diet containing saturated fat and cholesterol. The animals were fed diets containing 2% cholesterol and either 25% coconut oil (group I), 25% fish oil/coconut oil (1:1; group II), or 25% fish oil/coconut oil (3:1; group III) for 12 months (n = 8/group). Adding menhaden fish oil to the diet increased plasma eicosapentaenoic acid and docosahexaenoic acid and decreased plasma linoleic acid in animals fed the fish oil containing diets. Plasma concentrations of all lipoprotein fractions were decreased in the fish oil groups. VLDL isolated from group I animals exhibited beta-mobility on agarose gels but the VLDL from groups II and III animals did not. The group I VLDL was more highly enriched in cholesteryl ester than was VLDL from groups II and III. Group I LDL had a small but significant increase in cholesteryl ester content compared to group III LDL. No differences in HDL composition were observed in the 3 groups. At least 6 times less apo E was recovered in VLDL, IDL, and LDL from group III animals than from group I animals. Assuming 1 molecule of apo B per lipoprotein particle, there were 50% fewer VLDL, IDL, and LDL particles in group III than in group I animals. Group III also had significantly lower molar ratios of apo E/apo B in VLDL, IDL, and LDL than did group I animals. When VLDL from all 3 groups were incubated with J774 macrophages at equal protein concentrations, only the VLDL from the group I animals stimulated cholesterol esterification. Thus, introducing fish oil into an atherogenic diet reduced the number of VLDL, IDL and LDL particles in plasma by as much as 50%, reduced the cholesteryl ester content of the circulating lipoprotein, and reduced the ability of the VLDL to stimulate cholesterol esterification in macrophages.

  5. Effects of chronic methylphenidate on cocaine self-administration under a progressive-ratio schedule of reinforcement in rhesus monkeys.

    Science.gov (United States)

    Czoty, Paul W; Martelle, Susan E; Gould, Robert W; Nader, Michael A

    2013-06-01

    It has been hypothesized that drugs that serve as substrates for dopamine (DA) and norepinephrine (NE) transporters may be more suitable medications for cocaine dependence than drugs that inhibit DA and NE uptake by binding to transporters. Previous studies have shown that the DA/NE releaser d-amphetamine can decrease cocaine self-administration in preclinical and clinical studies. The present study examined the effects of methylphenidate (MPD), a DA uptake inhibitor, for its ability to decrease cocaine self-administration under conditions designed to reflect clinically relevant regimens of cocaine exposure and pharmacotherapy. Each morning, rhesus monkeys pressed a lever to receive food pellets under a fixed-ratio 50 schedule of reinforcement; cocaine was self-administered under a progressive-ratio schedule of reinforcement in the evening. After cocaine (0.003-0.56 mg/kg per injection, i.v.) dose-response curves were determined, self-administration sessions were suspended and MPD (0.003-0.0056 mg/kg per hour, i.v.; or 1.0-9.0 mg/kg p.o., b.i.d.) was administered for several weeks. A cocaine self-administration session was conducted every 7 days. When a MPD dose was reached that either persistently decreased cocaine self-administration or produced disruptive effects, the cocaine dose-effect curve was re-determined. In most cases, MPD treatment either produced behaviorally disruptive effects or increased cocaine self-administration; it took several weeks for these effects to dissipate. These data are consistent with the largely negative results of clinical trials with MPD. In contrast to the positive effects with the monoamine releaser d-amphetamine under identical conditions, these results do not support use of monoamine uptake inhibitors like MPD as a medication for cocaine dependence.

  6. 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.

  7. Measles virus selectively blind to signaling lymphocytic activation molecule (SLAM; CD150) is attenuated and induces strong adaptive immune responses in rhesus monkeys.

    Science.gov (United States)

    Leonard, Vincent H J; Hodge, Gregory; Reyes-Del Valle, Jorge; McChesney, Michael B; Cattaneo, Roberto

    2010-04-01

    The signaling lymphocytic activation molecule (SLAM; CD150) is the immune cell receptor for measles virus (MV). To assess the importance of the SLAM-MV interactions for virus spread and pathogenesis, we generated a wild-type IC-B MV selectively unable to recognize human SLAM (SLAM-blind). This virus differs from the fully virulent wild-type IC-B strain by a single arginine-to-alanine substitution at amino acid 533 of the attachment protein hemagglutinin and infects cells through SLAM about 40 times less efficiently than the isogenic wild-type strain. Ex vivo, this virus infects primary lymphocytes at low levels regardless of SLAM expression. When a group of six rhesus monkeys (Macaca mulatta) was inoculated intranasally with the SLAM-blind virus, no clinical symptoms were documented. Only one monkey had low-level viremia early after infection, whereas all the hosts in the control group had high viremia levels. Despite minimal, if any, viremia, all six hosts generated neutralizing antibody titers close to those of the control monkeys while MV-directed cellular immunity reached levels at least as high as in wild-type-infected monkeys. These findings prove formally that efficient SLAM recognition is necessary for MV virulence and pathogenesis. They also suggest that the selectively SLAM-blind wild-type MV can be developed into a vaccine vector.

  8. 实验猕猴肺部CT影像断层初步观察%Observation of Lung CT Tomography of the Laboratorial Rhesus Monkey

    Institute of Scientific and Technical Information of China (English)

    范春梅; 李志雄; 周建华

    2011-01-01

    Objective To research the clinical diagnosis of lung disease in rhesus monkey with the observation of lung CT tomography of the adult laboratorial rhesus monkey, to establish the maps of CT tomography of the healthy adult rhesus monkey, to provide the basic image data of CT technology in the applications of anatomy, clinical diagnosis and scientific experiments of rhesus monkey. Methods 5 male and 5 female health adult monkeys aged 5 ~ 10 yean were selected for this study of lung CT tomography after being checked by palpation, percussion, auscultation and by examination of body temperature, respiratory rate, heart rate, breathing motion and blood parameters. After general anesthesia, the monkeys were placed on the table-board of CT in supine position and were scanned to get the image of lung CT tomography. The main structure of every level in scanned images were labeled, tuch as lobe, trachea, arteries and veins,etc, Results (I) 13 anatomical images of lung CT tomography are obtained. (2) In the image of CT tomography, lung, trachea, large blood vessels arc all in focus. Lungs ore composed of the right put and (he left part, the left lung is divided into upper lobe, middle lube and luwer lobe. Right lung is divided into upper lobe, middle lobe, lower lobe and aiygos lobe. Left main bronchus. Right main bronchus, bronchial and vascular are very obvious in different scanned images- (3) Interfaces of small blood vessels, small nerves and muscle tissues ore no! Clearly defined on the CT Manned images. Conclusions (1) The images of lung CT tomogrphy of the healthy adult rhesus monkey show that all the lung lohes are absolutely clear, lung transmitancc is flood, and there are no any shadow,. (2)Obtained the anatomy CT tomography image datu of healthy aduft rhesus monkey. It can provide a new M&, convenient and accuralf hasis for diagnosia of monkey lung disease. It also established the background Information data of CT tomography anatomy of the healthy adult rhesus

  9. Analogues of simple and complex cells in rhesus monkey auditory cortex.

    Science.gov (United States)

    Tian, Biao; Kuśmierek, Paweł; Rauschecker, Josef P

    2013-05-01

    Receptive fields (RFs) of neurons in primary visual cortex have traditionally been subdivided into two major classes: "simple" and "complex" cells. Simple cells were originally defined by the existence of segregated subregions within their RF that respond to either the on- or offset of a light bar and by spatial summation within each of these regions, whereas complex cells had ON and OFF regions that were coextensive in space [Hubel DH, et al. (1962) J Physiol 160:106-154]. Although other definitions based on the linearity of response modulation have been proposed later [Movshon JA, et al. (1978) J Physiol 283:53-77; Skottun BC, et al. (1991) Vision Res 31(7-8):1079-1086], the segregation of ON and OFF subregions has remained an important criterion for the distinction between simple and complex cells. Here we report that response profiles of neurons in primary auditory cortex of monkeys show a similar distinction: one group of cells has segregated ON and OFF subregions in frequency space; and another group shows ON and OFF responses within largely overlapping response profiles. This observation is intriguing for two reasons: (i) spectrotemporal dissociation in the auditory domain provides a basic neural mechanism for the segregation of sounds, a fundamental prerequisite for auditory figure-ground discrimination; and (ii) the existence of similar types of RF organization in visual and auditory cortex would support the existence of a common canonical processing algorithm within cortical columns.

  10. 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.

  11. A new method for piercing the tentorium cerebelli for implanting fragile electrodes into the brain stem in the rhesus monkey (Macaca mulatta).

    Science.gov (United States)

    Wu, Jing; Wang, Wenchao; Rizak, Joshua Dominic; Wang, Zhengbo; Wang, Jianhong; Feng, Xiaoli; Dong, Jinrun; Li, Lin; Liu, Li; Xu, Liqi; Yang, Shangchuan; Hu, Xintian

    2014-03-01

    Recent developments in neuron recording techniques include the invention of some fragile electrodes. The fragility of these electrodes impedes their successful use in deep brain recordings because it is difficult to penetrate the electrodes through the dura mater, especially the tentorium cerebelli (TC) enclosing the cerebellum and brain stem. This paper reports a new method to pierce the TC for inserting fragile electrodes into the inferior colliculus of rhesus monkeys. Briefly, a unique tool kit, consisting of needles with sharp tips, a guide tube and an "impactor," was used in a multistep protocol to pierce the TC. The impactor provided a brief force that quickly thrusts the needles through the meninges without causing significant damage to the brain tissue under the TC. Using this novel approach, tetrodes were successfully implanted into the inferior colliculus of a rhesus monkey and neuronal discharge signals were recorded. This method, which is simple, convenient and economical, allows neurophysiologists to study the electrophysiological characteristics of deep brain structures under the TC with advanced, albeit fragile, electrodes.

  12. Quantitative assessment of timing, efficiency, specificity and genetic mosaicism of CRISPR/Cas9-mediated gene editing of hemoglobin beta gene in rhesus monkey embryos.

    Science.gov (United States)

    Midic, Uros; Hung, Pei-Hsuan; Vincent, Kailey A; Goheen, Benjamin; Schupp, Patrick G; Chen, Diane D; Bauer, Daniel E; VandeVoort, Catherine A; Latham, Keith E

    2017-07-15

    Gene editing technologies offer new options for developing novel biomedical research models and for gene and stem cell based therapies. However, applications in many species demand high efficiencies, specificity, and a thorough understanding of likely editing outcomes. To date, overall efficiencies, rates of off-targeting and degree of genetic mosaicism have not been well-characterized for most species, limiting our ability to optimize methods. As a model gene for measuring these parameters of the CRISPR/Cas9 application in a primate species (rhesus monkey), we selected the β-hemoglobin gene (HBB), which also has high relevance to the potential application of gene editing and stem-cell technologies for treating human disease. Our data demonstrate an ability to achieve a high efficiency of gene editing in rhesus monkey zygotes, with no detected off-target effects at selected off-target loci. Considerable genetic mosaicism and variation in the fraction of embryonic cells bearing targeted alleles are observed, and the timing of editing events is revealed using a new model. The uses of Cas9-WT protein combined with optimized concentrations of sgRNAs are two likely areas for further refinement to enhance efficiency while limiting unfavorable outcomes that can be exceedingly costly for application of gene editing in primate species. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Effects of monoamine releasers with varying selectivity for releasing dopamine/norepinephrine versus serotonin on choice between cocaine and food in rhesus monkeys.

    Science.gov (United States)

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

    2011-12-01

    Monoamine releasers constitute one class of candidate medications for the treatment of cocaine abuse, and concurrent cocaine-versus-food choice procedures are potentially valuable as experimental tools to evaluate the efficacy and safety of candidate medications. This study assessed the choice between cocaine and food by rhesus monkeys during treatment with five monoamine releasers that varied in selectivity to promote the release of dopamine and norepinephrine versus serotonin (5HT) [m-fluoroamphetamine, (+)-phenmetrazine, (+)-methamphetamine, napthylisopropylamine and (±)-fenfluramine]. Rhesus monkeys (n=8) responded under a concurrent-choice schedule of food delivery (1-g pellets, fixed ratio 100 schedule) and cocaine injections (0-0.1 mg/kg/injection, fixed ratio 10 schedule). Cocaine choice dose-effect curves were determined daily during continuous 7-day treatment with saline or with each test compound dose. During saline treatment, cocaine maintained a dose-dependent increase in cocaine choice, and the highest cocaine doses (0.032-0.1 mg/kg/injection) maintained almost exclusive cocaine choice. Efficacy of monoamine releasers to decrease cocaine choice corresponded to their pharmacological selectivity to release dopamine and norepinephrine versus 5HT. None of the releasers reduced cocaine choice or promoted reallocation of responding to food choice to the same extent as when saline was substituted for cocaine. These results extend the range of conditions across which dopamine and norepinephrine-selective releasers have been shown to reduce cocaine self-administration.

  14. [3D finite-element study on displacement of craniofacial complex with retractive forces parallel to the occlusion plane on the maxilla of rhesus monkeys].

    Science.gov (United States)

    Huang, Jiaxin; Zhang, Xiaorong; Yao, Ji

    2014-04-01

    To construct a 3D finite-element model of the craniofacial complex with the original DICOM data of CT and to investigate the preliminary biomechanical characteristics with different directions and magnitudes of retractive forces to the maxilla of rhesus monkeys. A male rhesus monkey with mixed dentition was used. Spiral CT was performed to establish a 3D finite-element model of the craniofacial complex. The ANSYS 12.1 software was used to analyze craniofacial complex displacement. Each landmark showed larger displacement with increasing force value. The displacement values and force size exhibited a linear relationship. In the x-axis direction, all displacements were small. In the y-axis direction, all displacements showed significantly higher changes with increasing force value displacement. In the z-axis direction, the A-point and ANS point moved downward, but PNS moved upward. Loading retractive force resultes in an apparent backward and clockwise rotation on the maxilla with no obvious effects on the width of the upper jaw.

  15. Clonal repertoires of virus-specific CD8+ T lymphocytes are shared in mucosal and systemic compartments during chronic simian immunodeficiency virus infection in rhesus monkeys.

    Science.gov (United States)

    Sircar, Piya; Furr, Kathryn L; Dorosh, Lauren A; Letvin, Norman L

    2010-08-15

    Because it is thought that mucosal tissues play a fundamental role in early HIV/SIV infection, it is crucial to understand the virus-specific responses in mucosal tissues to facilitate devising strategies to prevent and control these infections. We have employed TCR repertoire analyses to define the clonal composition of a dominant SIV epitope-specific CD8(+) T cell population in mucosal and systemic compartments of SIV-infected rhesus monkeys during both acute and chronic infection. We show that the CD8(+) T cell repertoire in mucosal tissues of uninfected rhesus monkeys is oligoclonal, whereas the CD8(+) T cell repertoire in blood is polyclonal. Early postinfection, the SIV-specific CD8(+) T cell clonal repertoire is distinct in mucosal compartments and peripheral blood. However, we observed a narrowing of the virus-specific CD8(+) T cell clonal repertoire in all sampled anatomic compartments as infection progressed from acute to chronic, and there was comparable clonal diversity in all anatomic compartments. We showed during chronic infection that the same clonal populations of virus-specific CD8(+) T cells are present in all compartments. These data indicate that the SIV-specific CD8(+) T cells in systemic and mucosal sites have a shared clonal origin and are, therefore, capable of both responding to infection in the systemic circulation and trafficking to mucosal tissues.

  16. Hypothalamic modulation of growth hormone secretion in the rhesus monkey: evidence from intracerebroventricular infusions of glucose, free fatty acid, and ketone bodies.

    Science.gov (United States)

    Quabbe, H J; Bumke-Vogt, C; Iglesias-Rozas, J R; Freitag, S; Breitinger, N

    1991-10-01

    To evaluate the hypothalamus as a possible site of metabolic modulation of GH secretion, we studied the GH response to insulin hypoglycemia (IHG) and nicotinic acid (NA)-induced FFA depression in the absence and presence of third ventricular (ivt) infusions of glucose, oleic acid (Ol-Ac), or beta-hydroxybutyrate (beta OHB). Four rhesus monkeys had been prepared for chronic remote iv and ivt infusions as well as blood sampling from the adjacent room. Statistical evaluation used a two-way analysis of variance and individual comparisons with Tukey's Studentized range test. The GH response (area under the curve +/- SE) to IHG was significantly reduced by a concomitant ivt glucose infusion (control, 1.0 +/- 0.1; IHG, 12.1 +/- 3.3; IHG plus ivt glucose, 7.0 +/- 1.2 microgram/L.120 min). The GH response to FFA depression was significantly reduced by ivt Ol-Ac or beta OHB infusion (control, 6.0 +/- 1.0; NA, 51.5 +/- 4.1; Na plus Ol-Ac, 81.2 +/- 1.3; NA plus beta OHB, 38.6 +/- 3.5 microgram/L.300 min). Introcerebroventricular infusions of glucose, Ol-Ac, or beta OHB alone had no effect on plasma GH, glucose, FFA, or beta OHB concentrations. These results provide evidence for a hypothalamic site of metabolic modulation of GH secretion in the rhesus monkey. This does not exclude an additional effect directly at the pituitary gland.

  17. Inducible nitric oxide synthase in heart tissue and nitric oxide in serum of Trypanosoma cruzi-infected rhesus monkeys: association with heart injury.

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    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

  18. 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

  19. 3~4岁猕猴生理指标的测定%Determination of Physiological Parameters in Juvenile Rhesus Monkeys

    Institute of Scientific and Technical Information of China (English)

    邢凤英; 严国锋; 杨伟敏; 陈学进; 李垚

    2013-01-01

    Objectives To detect the physiological parameters of juvenile rhesus monkeys.Method One hundred healthy 3 to 4-year-old juvenile rhesus monkeys (♂ 50,♀ 50)were measured for a comprehensive examination about their hematological,cardiopulmonary function and other physiological parameters,including 30 routine blood tests,22 blood biochemical indexes,2 blood coagulation tests as well as blood pressure,electrocardiogram and respiratory rate.Result Mean corpuscular hemoglobin concentration (MCHC) (P<0.01) in the female rhesus monkeys was significantly lower than that of male monkeys;whereas platelet count (PLT),thrombocytocrit (PCT),eosinophil(EO),basophilic granulocyte (BASO),EO percentage (%),BASO percentage(%) (P<0.01) and white blood cell count (WBC),lymphocyte count (LYMPH) (P<0.05) were significantly higher in females juvenile rhesus monkeys than those of males.For the blood biochemical parameters,urea nitrogen (BUN),total bilirubin (TBIL),γ-glutamyl transpeptidase (γ-GTP),inorganic phosphorus (IP) (P<0.01) and glutamic-oxalacetic transaminease (AST),albumin (ALB),bilirubin (Total & Direct) (DBIL) (P<0.05) was significantly lower in the female than in male; while glucose (GLU),calcium (Ca) and triglycercide (TG) was significantly higher in females than in males (P<0.05).There were no significant differences in parameters considering blood coagulation tests,blood pressure and electrocardiogram between male and female juvenile rhesus monkeys.Respiratory rate was significantly reduced in female than in male (P<0.01).Conclusion The physiological biochemical parameters in experimental juvenile rhesus monkeys which might provide basis for reference values for animal experiments and disease diagnosis using juvenile rhesus monkeys.%目的 建立3~4岁猕猴生理指标基础数据.方法 对100只3~4岁猕猴(♂ 50只,♀50只)进行了较全面的血液学和心肺功能等生理指标的测定,包括血常规30项、血液生化22

  20. Behavioral inhibition in rhesus monkeys (Macaca mulatta is related to the airways response, but not immune measures, commonly associated with asthma.

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    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

  1. Determination and analysis of the complete genomic sequence of avian hepatitis E virus (avian HEV) and attempts to infect rhesus monkeys with avian HEV.

    Science.gov (United States)

    Huang, F F; Sun, Z F; Emerson, S U; Purcell, R H; Shivaprasad, H L; Pierson, F W; Toth, T E; Meng, X J

    2004-06-01

    Avian hepatitis E virus (avian HEV), recently identified from a chicken with hepatitis-splenomegaly syndrome in the United States, is genetically and antigenically related to human and swine HEVs. In this study, sequencing of the genome was completed and an attempt was made to infect rhesus monkeys with avian HEV. The full-length genome of avian HEV, excluding the poly(A) tail, is 6654 bp in length, which is about 600 bp shorter than that of human and swine HEVs. Similar to human and swine HEV genomes, the avian HEV genome consists of a short 5' non-coding region (NCR) followed by three partially overlapping open reading frames (ORFs) and a 3'NCR. Avian HEV shares about 50 % nucleotide sequence identity over the complete genome, 48-51 % identity in ORF1, 46-48 % identity in ORF2 and only 29-34 % identity in ORF3 with human and swine HEV strains. Significant genetic variations such as deletions and insertions, particularly in ORF1 of avian HEV, were observed. However, motifs in the putative functional domains of ORF1, such as the helicase and methyltransferase, were relatively conserved between avian HEV and mammalian HEVs, supporting the conclusion that avian HEV is a member of the genus Hepevirus. Phylogenetic analysis revealed that avian HEV represents a branch distinct from human and swine HEVs. Swine HEV infects non-human primates and possibly humans and thus may be zoonotic. An attempt was made to determine whether avian HEV also infects across species by experimentally inoculating two rhesus monkeys with avian HEV. Evidence of virus infection was not observed in the inoculated monkeys as there was no seroconversion, viraemia, faecal virus shedding or serum liver enzyme elevation. The results from this study confirmed that avian HEV is related to, but distinct from, human and swine HEVs; however, unlike swine HEV, avian HEV is probably not transmissible to non-human primates.

  2. The sweetness-inducing effect of miraculin; behavioural and neurophysiological experiments in the rhesus monkey Macaca mulatta.

    Science.gov (United States)

    Brouwer, J N; Glaser, D; Hard Af Segerstad, C; Hellekant, G; Ninomiya, Y; Van der Wel, H

    1983-04-01

    1. The gustatory effects of miraculin, the sweetness-inducing protein from the miracle fruit Synsepalum dulcificum, was studied in the rhesus monkey, Macaca mulatta.2. The intake of five acids was recorded in two-bottle preference tests, one bottle containing acid and the other tap water, before and after miraculin treatment. All the acids tasted more pleasant after miraculin.3. The electrical activity of the chorda tympani nerve to stimulation of the tongue with a variety of sweeteners, acids, sodium chloride and quinine hydrochloride was recorded in anaesthetized animals.4. Pre-treatment of the tongue with 0.3-5 mg miraculin doubled the summated nerve response to the acids and diminished the response to sucrose by about 10%. The enhancement lasted for at least an hour and the diminution up to 20 min.5. After miraculin treatment the Spearman's rank correlation coefficient between the order of increased intake of acids and the order of enhancement of the summated nerve response was 0.99.6. A solution of 0.1 mg miraculin per ml. elicited a weak nerve response. No preference over water for this concentration of miraculin was recorded in the two-bottle tests.7. The activity of twenty-nine single taste fibres, selected for their responsiveness to sweetness or acids or both, was recorded after miraculin treatment. Effects were obtained in nine fibres which were similar but more pronounced than those observed in the summated recordings. Before miraculin, these fibres responded better and to a larger variety of sweeteners (81%) than the other fibres (40%). After miraculin, acids elicited on the average 2.3 times more activity than before, while the response to sweeteners was depressed. In twenty fibres no effect of miraculin was observed. These fibres responded to fewer of the sweeteners and were more stimulated by the non-sweet stimuli than the first group.8. The results suggest that miraculin acts on those structures in the taste cell membrane that are involved in

  3. Limited replication of yellow fever 17DD and 17D-Dengue recombinant viruses in rhesus monkeys

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    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

  4. Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on high-fat, high-sugar diet.

    Science.gov (United States)

    Jimenez-Gomez, Yolanda; Mattison, Julie A; Pearson, Kevin J; Martin-Montalvo, Alejandro; Palacios, Hector H; Sossong, Alex M; Ward, Theresa M; Younts, Caitlin M; Lewis, Kaitlyn; Allard, Joanne S; Longo, Dan L; Belman, Jonathan P; Malagon, Maria M; Navas, Placido; Sanghvi, Mitesh; Moaddel, Ruin; Tilmont, Edward M; Herbert, Richard L; Morrell, Christopher H; Egan, Josephine M; Baur, Joseph A; Ferrucci, Luigi; Bogan, Jonathan S; Bernier, Michel; de Cabo, Rafael

    2013-10-01

    Obesity is associated with a chronic, low-grade, systemic inflammation that may contribute to the development of insulin resistance and type 2 diabetes. Resveratrol, a natural compound with anti-inflammatory properties, is shown to improve glucose tolerance and insulin sensitivity in obese mice and humans. Here, we tested the effect of a 2-year resveratrol administration on proinflammatory profile and insulin resistance caused by a high-fat, high-sugar (HFS) diet in white adipose tissue (WAT) from rhesus monkeys. Resveratrol supplementation (80 and 480 mg/day for the first and second year, respectively) decreased adipocyte size, increased sirtuin 1 expression, decreased NF-κB activation, and improved insulin sensitivity in visceral, but not subcutaneous, WAT from HFS-fed animals. These effects were reproduced in 3T3-L1 adipocytes cultured in media supplemented with serum from monkeys fed HFS ± resveratrol diets. In conclusion, chronic administration of resveratrol exerts beneficial metabolic and inflammatory adaptations in visceral WAT from diet-induced obese monkeys.

  5. 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

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    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.

  6. Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on a high-fat, high-sugar diet

    Science.gov (United States)

    Jimenez-Gomez, Yolanda; Mattison, Julie A.; Pearson, Kevin J.; Martin-Montalvo, Alejandro; Palacios, Hector H.; Sossong, Alex M.; Ward, Theresa M.; Younts, Caitlin M.; Lewis, Kaitlyn; Allard, Joanne S.; Longo, Dan L.; Belman, Jonathan P.; Malagon, Maria M.; Navas, Placido; Sanghvi, Mitesh; Moaddel, Ruin; Tilmont, Edward M.; Herbert, Richard L.; Morrell, Christopher H.; Egan, Josephine M.; Baur, Joseph A.; Ferrucci, Luigi; Bogan, Jonathan S.; Bernier, Michel; de Cabo, Rafael

    2013-01-01

    SUMMARY Obesity is associated with a chronic, low-grade, systemic inflammation that may contribute to the development of insulin resistance and type 2 diabetes. Resveratrol, a natural compound with anti-inflammatory properties, is shown to improve glucose tolerance and insulin sensitivity in obese mice and humans. Here we tested the effect of a 2-year resveratrol administration on pro-inflammatory profile and insulin resistance caused by a high-fat, high-sugar (HFS) diet in white adipose tissue (WAT) from rhesus monkeys. Eighty mg/day of resveratrol for 12-month followed by 480 mg/day for the second year decreased adipocyte size, increased sirtuin 1 expression, decreased NF-κB activation and improved insulin sensitivity in visceral but not subcutaneous WAT from HFS-fed animals. These effects were reproduced in 3T3-L1 adipocytes cultured in media supplemented with serum from monkeys fed HFS +/− resveratrol diets. In conclusion, chronic administration of resveratrol exerts beneficial metabolic and inflammatory adaptations in visceral WAT from diet-induced obese monkeys. PMID:24093677

  7. 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...

  8. Alloimmunization due to red cell antibodies in Rhesus positive Omani Pregnant Women: Maternal and Perinatal outcome

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    Tamima Al-Dughaishi

    2015-01-01

    Full Text Available Objective: This study is aimed to determine the prevalence of alloimmunization due to antibodies to red blood cell (RBC antigens (other than rhesus [Rh] antigen and report the maternal, perinatal, and neonatal outcomes. Materials and Methods: A retrospective review of medical records of all patients with minor RBCs antibodies alloimmunization who were followed and delivered at Sultan Qaboos University Hospital, Oman from June 2011 to June 2013. Maternal characteristics, antibody type, antibody titer in addition to perinatal and neonatal outcomes were reviewed. Results: There were 1160 patients with Rh positive status in the study. The most common ABO blood group was O, followed by A, B, and AB. We found 33 out of 1160 Rh positive women alloimmunized with minor RBCs antibodies that gave a prevalence of minor RBCs alloimmunization of 2.7%. The most frequent antibody was anti-E 38%, followed by anti-c 17% and anti-kell 17%. 6 of these 33 patients were identified to have significant antibody titer, and two cases showed evidence of fetal anemia. Only one case required an intrauterine blood transfusion. The most common neonatal complication was jaundice in 53%, followed by respiratory distress syndrome in 28%. Two cases complicated by neonatal anemia required a postnatal blood transfusion. Conclusion: Alloimmunization with anti-E, anti-c, and anti-kell were the most common antibodies among the study group. Minor RBCs alloimmunization was an important cause of neonatal morbidity.

  9. Effects of chronic exposure to 2, 3, 7, 8,-tetrachlorodibenzo-p-dioxin on sister chromatid exchange levels in peripheral lymphocytes of the rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Lim, M.; Jacobson-Kram, D.; Bowman, R.E.; Williams, J.R.

    1987-01-01

    Frequencies of sister chromatid exchanges and chromosomal aberrations were examined in peripheral lymphocytes of Rhesus monkeys that had been fed a diet containing 25 parts per trillion 2,3,7,8-tetrachlorodibenzo-p-dioxin for a period of 4 years. When compared to non-exposed control animals, no significant differences were noted for either of these cytogenetic end points. In addition, there was not a significant difference in sister chromatid exchange response to a challenge dose of mitomycin C in cells from 2,3,7,8-tetrachlorodibenzo-p-dioxin exposed animals compared to controls. The results confirm the lack of genotoxic effects associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure.

  10. 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.

  11. Procedures for the isolation and culture of Sertoli cells from the testes of infant, juvenile, and adult rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Majumdar, S S; Winters, S J; Plant, T M

    1998-03-01

    The purpose of the present study was to establish culture conditions for the in vitro study of the rhesus monkey Sertoli cell (Sc) at three major stages of development, namely infancy, adulthood, and the intervening prepubertal period. Conditions for the culture of Sc from juveniles were first established using collagenase and pancreatin digestion of seminiferous tubules. The addition of 1% fetal bovine serum for the first 24 h of culture was necessary for attachment of Sc clusters. Confluency of Sc from juveniles was reached as early as 4 days of culture. Histochemical and ultrastructural observations confirmed that the cultures were enriched with Sc and that contamination by peritubular cells was minimal (2%). Although application of similar culture conditions was successful in establishing cultures of Sc from infants, significant modification of the procedure was required before Sc from adults could be cultured. Specifically, adult testicular tissue required two sequential collagenase digestions at elevated temperature. The yield of adult Sc, however, remained low. Cultures of juvenile Sc produced substantial quantities of 31-kDa inhibin, which was bioactive as reflected by its ability to suppress FSH secretion from rat pituitary cells in vitro. Although aromatase activity in juvenile Sc cultures was stimulated by FSH, inhibin synthesis, as reflected by immunoactive inhibin production and steady-state levels of alpha inhibin mRNA, was not increased by FSH. The establishment of conditions for the culture of infant, juvenile, and adult Sc from the rhesus monkey will provide a model for study of the postnatal ontogeny of Sc function in higher primates.

  12. Perseverative Interference with Object-in-Place Scene Learning in Rhesus Monkeys with Bilateral Ablation of Ventrolateral Prefrontal Cortex

    Science.gov (United States)

    Baxter, Mark G.; Browning, Philip G. F.; Mitchell, Anna S.

    2008-01-01

    Surgical disconnection of the frontal cortex and inferotemporal cortex severely impairs many aspects of visual learning and memory, including learning of new object-in-place scene memory problems, a monkey model of episodic memory. As part of a study of specialization within prefrontal cortex in visual learning and memory, we tested monkeys with…

  13. 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

  14. Rhesus monkeys kidney cells persistently infected with Simian Virus 40: production of defective interfering virus and acquisition of the transformed phenotype.

    Science.gov (United States)

    Norkin, L C

    1976-09-01

    Monolayer cultures of LLC-MK2 rhesus monkey kidney cells became persistently infected with simian virus 40 (SV40) when infected at a multiplicity of infection of 100 plaque-forming units/cell. A stable carrier state developed characterized by extensive viral proliferation without obvious cytopathic effect other than the slow growth of these cultures. By 11 weeks all cells produced the SV40 T antigen. In contrast, less than 5% of the cells produced V antigen. Virus-free clonal isolates were obtained by cloning in SV40 antiserum. Continuous cultivation in antiserum resulted in a temporary cure of unclone cultures. When virus did eventually reappear in the "cured" cultures the titers remained low. The virus produced by the carrier culture was defective at both 31 and 37% c, and it interfered with the growth of standard s40 during mixed infection of CV-1 green monkey kidney cells. All of the interfering activity in carrier culture homogenates could be sedimented by centrifugation at 109,000 x g for 3 h. These cultures were completely susceptible to vesicular stomatitis virus. Extensive viral deoxyribonucleic acid synthesis occurred in CV-1 cells infected with carrier culture virus. Carrier culture homogenates are only slightly less cytopathic to CV-1 cells than standard SV40. The carrier culture express several properties of SV40 transformation.

  15. 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)

  16. A generalized matching law analysis of cocaine vs. food choice in rhesus monkeys: effects of candidate 'agonist-based' medications on sensitivity to reinforcement.

    Science.gov (United States)

    Hutsell, Blake A; Negus, S Stevens; Banks, Matthew L

    2015-01-01

    We have previously demonstrated reductions in cocaine choice produced by either continuous 14-day phendimetrazine and d-amphetamine treatment or removing cocaine availability under a cocaine vs. food choice procedure in rhesus monkeys. The aim of the present investigation was to apply the concatenated generalized matching law (GML) to cocaine vs. food choice dose-effect functions incorporating sensitivity to both the relative magnitude and price of each reinforcer. Our goal was to determine potential behavioral mechanisms underlying pharmacological treatment efficacy to decrease cocaine choice. A multi-model comparison approach was used to characterize dose- and time-course effects of both pharmacological and environmental manipulations on sensitivity to reinforcement. GML models provided an excellent fit of the cocaine choice dose-effect functions in individual monkeys. Reductions in cocaine choice by both pharmacological and environmental manipulations were principally produced by systematic decreases in sensitivity to reinforcer price and non-systematic changes in sensitivity to reinforcer magnitude. The modeling approach used provides a theoretical link between the experimental analysis of choice and pharmacological treatments being evaluated as candidate 'agonist-based' medications for cocaine addiction. The analysis suggests that monoamine releaser treatment efficacy to decrease cocaine choice was mediated by selectively increasing the relative price of cocaine. Overall, the net behavioral effect of these pharmacological treatments was to increase substitutability of food pellets, a nondrug reinforcer, for cocaine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. A touch screen based Stop Signal Response Task in rhesus monkeys for studying impulsivity associated with chronic cocaine self-administration.

    Science.gov (United States)

    Liu, Shijing; Heitz, Richard P; Bradberry, Charles W

    2009-02-15

    Among a range of cognitive deficits, human cocaine addicts display increased impulsivity and decreased performance monitoring. In order to establish an animal model that can be used to study the underlying neurobiology of these deficits associated with addiction, we have developed a touch screen based Stop Signal Response Task for rhesus monkeys. This task is essentially identical to the clinically used Stop Signal Task employed for diagnostic and research purposes. In this task, impulsivity is reflected in the amount of time needed to inhibit a response after it has been initiated, the Stop Signal Response Time (SSRT). Performance monitoring is reflected by the slowing of response times following Stop trials (Post-Stop Slowing, PSS). Herein we report on the task structure, the staged methods for training animals to perform the task, and a comparison of performance values for control and cocaine experienced animals. Relative to controls, monkeys that had self-administered cocaine, followed by 18 months abstinence, displayed increased impulsivity (increased SSRT values), and decreased performance monitoring (decreased PSS values). Our results are consistent with human data, and thereby establish an ideal animal model for studying the etiology and underlying neurobiology of cocaine-induced impulse control and performance monitoring deficits.

  18. Observation on Chest Big Vascular System of Rhesus Monkey by Three-dimensional Spiral CT Reconstruction%螺旋CT三维重建观察实验猕猴胸部大血管系统

    Institute of Scientific and Technical Information of China (English)

    范春梅; 李志雄; 车敏

    2012-01-01

    目的 利用256层螺旋CT三维重建观察实验猕猴胸部大血管,为猕猴血管系统的研究、数字化猴的建立及科学研究提供资料.方法 (1)选择实验猕猴10只,雌雄各半,年龄6~10岁,进行胸部CT断层扫描试验.(2)动物全身麻醉后,采用平扫及增强扫描技术,进行容积数据采集,获取正常猕猴胸部CT横断面影像.(3)利用CT图像后处理技术对扫描获得的容积数据进行三维的图像重组处理.结果 获得了良好的主动脉、肺动静脉等胸部大血管三维重建的立体影像,本文展示了2幅三维重组图像.从比较解剖学的角度,观察到了猕猴胸部血管的结构特点及与人类的区别.结论 CT三维重建能很好地反映了猕猴胸部血管系统的解剖结构、走行及与周围结构的位置关系,它是有效的、无创伤性的、直观的观察血管系统的理想方法.%Objective Observing rhesus monkey big vascular system of chest by 256 layer spiral CT and providing scientific materials for studying rhesus monkey vascular and digitization system. Methods Five male and five female rhesus monkeys aging at 6 to 10 years old were selected and obtained for CT scanning experiment. Rhesus monkey chest CT cross-sectional images were acquired through flat and strengthen scanning technique to collect volume data. Rhesus monkey volume data were processed by 3D image restruction using CT image post-processing technology. Results Rhesus monkey stereoscopic images of aorta, pulmonary artery and vein and chest big vascular were obtained by Three-dimensional reconstruction. From the point of comparative anatomy the difference of chest big vascular system between rhesus monkey and human being were found. Conclusion The anatomical and tissue structures of rhesus monkey among the big vascular system were reflected perfectly by Three-dimensional CT reconstruction. It is an effective, non-invasive and direct ideal way of observation of the vascular system.

  19. Effects of 7-day repeated treatment with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in male rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L

    2016-08-01

    Preclinical drug vs. food choice is an emerging group of drug self-administration procedures that have shown predictive validity to clinical drug addiction. Emerging data suggest that serotonin (5-HT)2A receptors modulate mesolimbic dopamine function, such that 5-HT2A antagonists blunt the abuse-related neurochemical effects of monoamine transporter substrates, such as amphetamine or methamphetamine. Whether subchronic 5-HT2A antagonist treatment attenuates methamphetamine reinforcement in any preclinical drug self-administration procedure is unknown. The study aim was therefore to determine 7-day treatment effects with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in monkeys. Behavior was maintained under a concurrent schedule of food delivery (1g pellets, fixed-ratio 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=3). Methamphetamine choice dose-effect functions were determined daily before and during 7-day repeated pimavanserin (1.0-10mg/kg/day, intramuscular) treatment periods. Under control conditions, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Repeated pimavanserin administration failed to attenuate methamphetamine choice and produce a reciprocal increase in food choice in any monkey up to doses (3.2-10mg/kg) that suppressed rates of operant responding primarily during components where behavior was maintained by food pellets. Repeated 5-HT2A receptor inverse agonist/antagonist treatment did not attenuate methamphetamine reinforcement under a concurrent schedule of intravenous methamphetamine and food presentation in nonhuman primates. Overall, these results do not support the therapeutic potential of 5-HT2A inverse agonists/antagonists as candidate medications for methamphetamine addiction. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights

  20. Reinforcing Effects Of Compounds Lacking Intrinsic Efficacy At α1 Subunit-Containing GABAA Receptor Subtypes in Midazolam- But Not Cocaine-Experienced Rhesus Monkeys

    Science.gov (United States)

    Shinday, Nina M; Sawyer, Eileen K; Fischer, Bradford D; Platt, Donna M; Licata, Stephanie C; Atack, John R; Dawson, Gerard R; Reynolds, David S; Rowlett, James K

    2013-01-01

    Benzodiazepines are prescribed widely but their utility is limited by unwanted side effects, including abuse potential. The mechanisms underlying the abuse-related effects of benzodiazepines are not well understood, although α1 subunit-containing GABAA receptors have been proposed to have a critical role. Here, we examine the reinforcing effects of several compounds that vary with respect to intrinsic efficacy at α2, α3, and α5 subunit-containing GABAA receptors but lack efficacy at α1 subunit-containing GABAA receptors (‘α1-sparing compounds'): MRK-623 (functional selectivity for α2/α3 subunit-containing receptors), TPA023B (functional selectivity for α2/α3/α5 subunit-containing receptors), and TP003 (functional selectivity for α3 subunit-containing receptors). The reinforcing effects of the α1-sparing compounds were compared with those of the non-selective benzodiazepine receptor partial agonist MRK-696, and non-selective benzodiazepine receptor full agonists, midazolam and lorazepam, in rhesus monkeys trained to self-administer midazolam or cocaine, under a progressive-ratio schedule of intravenous (i.v.) drug injection. The α1-sparing compounds were self-administered significantly above vehicle levels in monkeys maintained under a midazolam baseline, but not under a cocaine baseline over the dose ranges tested. Importantly, TP003 had significant reinforcing effects, albeit at lower levels of self-administration than non-selective benzodiazepine receptor agonists. Together, these results suggest that α1 subunit-containing GABAA receptors may have a role in the reinforcing effects of benzodiazepine-type compounds in monkeys with a history of stimulant self-administration, whereas α3 subunit-containing GABAA receptors may be important mediators of the reinforcing effects of benzodiazepine-type compounds in animals with a history of sedative-anxiolytic/benzodiazepine self-administration. PMID:23303046

  1. 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.

  2. Positron emission tomography in drug evaluation: Influence of three different catechol-O-methyltransferase inhibitors on metabolism of [NCA] 6-[{sup 18}F]fluoro-l-dopa in Rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, I.; Psylla, M.; Reddy, G.N.; Antonini, A.; Vontobel, P.; Reist, H.W.; Zollinger, A.; Nickles, R.J.; Beer, H.-F.; Schubiger, P.A.; Leenders, K.L

    1995-10-01

    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-[{sup 18}F]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.

  3. 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

  4. 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.

  5. Viral FGARAT Homolog ORF75 of Rhesus Monkey Rhadinovirus Effects Proteasomal Degradation of the ND10 Components SP100 and PML

    Science.gov (United States)

    Hahn, Alexander S.; Großkopf, Anna K.; Jungnickl, Doris; Scholz, Brigitte

    2016-01-01

    ABSTRACT Nuclear domain 10 (ND10) components restrict herpesviral infection, and herpesviruses antagonize this restriction by a variety of strategies, including degradation or relocalization of ND10 proteins. The rhesus monkey rhadinovirus (RRV) shares many key biological features with the closely related Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8) and readily infects cells of both human and rhesus monkey origin. We used the clustered regularly interspaced short palindromic repeat-Cas9 (CRISPR-Cas9) technique to generate knockout (ko) cells for each of the four ND10 components, PML, SP100, DAXX, and ATRX. These ko cells were analyzed with regard to permissiveness for RRV infection. In addition, we analyzed the fate of the individual ND10 components in infected cells by immunofluorescence and Western blotting. Knockout of the ND10 component DAXX markedly increased RRV infection, while knockout of PML or SP100 had a less pronounced effect. In line with these observations, RRV infection resulted in rapid degradation of SP100, followed by degradation of PML and the loss of ND10 structures, whereas the protein levels of ATRX and DAXX remained constant. Notably, inhibition of the proteasome but not inhibition of de novo gene expression prevented the loss of SP100 and PML in cells that did not support lytic replication, compatible with proteasomal degradation of these ND10 components through the action of a viral tegument protein. Expression of the RRV FGARAT homolog ORF75 was sufficient to effect the loss of SP100 and PML in transfected or transduced cells, implicating ORF75 as the viral effector protein. IMPORTANCE Our findings highlight the antiviral role of ND10 and its individual components and further establish the viral FGARAT homologs of the gammaherpesviruses to be important viral effectors that counteract ND10-instituted intrinsic immunity. Surprisingly, even closely related viruses like KSHV and RRV evolved to use different strategies to

  6. Isolation and Identification of BDNF in Cortex of Adult Rhesus Monkey and Its Distribution%成年恒河猴大脑皮质BDNF分离、鉴定及其分布

    Institute of Scientific and Technical Information of China (English)

    李玉; 王波; 王廷华; 习杨彦彬

    2011-01-01

    Objective To isolate and identify brain derived neurotrophic factor (BDNF) in the cerebral cortex of adult Rhesus monkey, and investigate its histological distribution. Methods The cortex tissues of monkeys were harvested, homogenized and isolated by SDS PAGE electrophoresis, and identified by western blot using rabbit BDNF specific antibody. Then the frozen sections from cortex were prepared, and the immunohistoebemistry method was used to detect the distribution of BDNF in the cerebral cortex of adult Rhesus monkey. The biological function of BDNF was discussed. Results After electrophoresis, Western blot showed that a specific band for BDNF located in 14KD molecule weight was recognized from the homogenization of monkey cortex. The BDNF immunopositive reaction was seen in the plasma and neurite of neurons in the layer Ⅲ and Ⅴ cerebral cortex of monkey. Conclusions Electrophoresis can isolate many proteins from the cerebral cortex of Rhesus monkey. BDNF can be recognized and indenfified by Western blot. BDNF is localized in the neurons of the cerebral cortex of monkey, suggestsing that BDNF may be a crucial molecule in the functional maintainence of CNS in adult monkeys.%目的 分离、鉴定成年恒河猴大脑皮质BDNF,并探讨其组织分布.方法 取成年恒河猴大脑皮质组织,匀浆制作蛋白提取液,SDS-PAGE电泳分离,Western blot鉴定.进而制作猴大脑皮质冰冻切片, 用BDNF抗体行免疫组织化学SP 法染色, 观察BDNF免疫阳性反应在成年恒河猴大脑皮质的分布,探讨BDNF的生物学功能.结果 电泳分离后,Western blot检测到分子量14 kD左右有BDNF特异阳性染色条带.免疫组化染色显示猴脑皮质第III和第V层神经元胞浆和突起均有BDNF染色.结论 电泳可分离恒河猴大脑皮质多种蛋白质,其中BDNF能通过Western blot识别鉴定;BDNF主要定位猴脑皮质神经元,提示其在灵长类皮质神经元功能维持中的重要作用.

  7. Exacerbation of Glycoprotein VI-Dependent Platelet Responses in a Rhesus Monkey Model of Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    J. F. Arthur

    2013-01-01

    Full Text Available Thrombosis is a life-threatening complication of diabetes. Platelet reactivity is crucial to thrombus formation, particularly in arterial vessels and in thrombotic complications causing myocardial infarction or ischaemic stroke, but diabetic patients often respond poorly to current antiplatelet medication. In this study, we used a nonhuman primate model of Type 1 diabetes to measure early downstream signalling events following engagement of the major platelet collagen receptor, glycoprotein (GPVI. Diabetic monkeys were given enough insulin to maintain their blood glucose levels either at ~8 mM (well-controlled diabetes or ~15 mM (poorly controlled diabetes. Flow cytometric analysis was used to measure platelet reactive oxygen species (ROS generation, calcium mobilisation, receptor surface expression, and immature platelet fraction. We observed exacerbated intracellular ROS and calcium flux associated with engagement of GPVI in monkeys with poorly controlled diabetes. GPVI surface levels did not differ between healthy monkeys or the two diabetic groups. Treatment of platelets with the specific Syk inhibitor BAY61-3606 inhibited GPVI-dependent ROS and, importantly, reduced ROS generation in the poorly controlled diabetes group to that observed in healthy monkeys. These data indicate that glycaemic control is important in reducing GPVI-dependent platelet hyperreactivity and point to a potential antithrombotic therapeutic benefit of Syk inhibition in hyperglycaemic diabetes.

  8. Time course and role of LH and FSH in the expansion of the Leydig cell population at the time of puberty in the rhesus monkey (Macaca mulatta)

    Science.gov (United States)

    Verhagen, I.; Ramaswamy, S.; Teerds, K.J.; Keijer, J.; Plant, T. M.

    2014-01-01

    In higher primates development of the adult population of Leydig cells has received little attention. Here, the emergence of 3β-hydroxysteroid dehydrogenase (HSD3B) positive cells in the testis of the rhesus monkey was examined during spontaneous puberty, and correlated with S-phase labeling in the interstitium at this critical stage of development. In addition, the relative role of LH and FSH in initiating the pubertal expansion of Leydig cells was studied by precociously stimulating the juvenile testis in vivo with pulsatile 11-day infusions of recombinant LH and FSH, either alone or in combination. At the time of castration, testes were immersion fixed in Bouin’s, embedded in paraffin and sectioned at 5 μm. Leydig cells/testis were enumerated using HSD3B as a Leydig cell marker. Leydig cell number per testis increased progressively during puberty to reach values in the adult approximately 10 fold greater than in early pubertal animals. The rise in cell number was associated with an increase in nuclear diameter. That the pubertal expansion of Leydig cell number was driven primarily by the increase in LH secretion at this stage of development was suggested by the finding that precocious stimulation of mid juvenile monkeys with LH, either alone or in combination with that of FSH, resulted in a 20 to 30 fold increase in the number of HSD3B positive cells. Interestingly, precocious FSH stimulation, alone, also resulted in appearance of Leydig cells as indicated by the occasional HSD3B positive cell in the interstitium. The nuclear diameter of these Leydig cells, however was less than that of those generated in response to LH. PMID:25269763

  9. Effects of 7-day continuous D-amphetamine, methylphenidate, and cocaine treatment on choice between methamphetamine and food in male rhesus monkeys.

    Science.gov (United States)

    Schwienteck, Kathryn L; Banks, Matthew L

    2015-10-01

    Methamphetamine addiction is a significant public health problem for which no Food and Drug Administration-approved pharmacotherapies exist. Preclinical drug vs. food choice procedures have been predictive of clinical medication efficacy in the treatment of opioid and cocaine addiction. Whether preclinical choice procedures are predictive of candidate medication effects for other abused drugs, such as methamphetamine, remains unclear. The present study aim was to determine continuous 7-day treatment effects with the monoamine releaser d-amphetamine and the monoamine uptake inhibitor methylphenidate on methamphetamine vs. food choice. In addition, 7-day cocaine treatment effects were also examined. Behavior was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and methamphetamine injections (0-0.32mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=4). Methamphetamine choice dose-effect functions were determined daily before and during 7-day periods of continuous intravenous treatment with d-amphetamine (0.01-0.1mg/kg/h), methylphenidate (0.032-0.32mg/kg/h), or cocaine (0.1-0.32mg/kg/h). During saline treatment, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Continuous 7-day treatments with d-amphetamine, methylphenidate or cocaine did not significantly attenuate methamphetamine vs. food choice up to doses that decreased rates of operant responding. However, 0.1mg/kg/h d-amphetamine did eliminate methamphetamine choice in two monkeys. The present subchronic treatment results support the utility of preclinical methamphetamine choice to evaluate candidate medications for methamphetamine addiction. Furthermore, these results confirm and extend previous results demonstrating differential pharmacological mechanisms between cocaine choice and methamphetamine choice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Effects of 7-day continuous d-amphetamine, methylphenidate, and cocaine treatment on choice between methamphetamine and food in male rhesus monkeys*

    Science.gov (United States)

    Schwienteck, Kathryn L.; Banks, Matthew L.

    2015-01-01

    Background Methamphetamine addiction is a significant public health problem for which no Food and Drug Administration-approved pharmacotherapies exist. Preclinical drug vs. food choice procedures have been predictive of clinical medication efficacy in the treatment of opioid and cocaine addiction. Whether preclinical choice procedures are predictive of candidate medication effects for other abused drugs, such as methamphetamine, remains unclear. The present study aim was to determine continuous 7-day treatment effects with the monoamine releaser d-amphetamine and the monoamine uptake inhibitor methylphenidate on methamphetamine vs. food choice.In addition, 7-day cocaine treatment effects were also examined. Methods Behavior was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and methamphetamine injections (0-0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=4). Methamphetamine choice dose-effect functions were determined daily before and during 7-day periods of continuous intravenous treatment with d-amphetamine (0.01-0.1 mg/kg/h), methylphenidate (0.032-0.32 mg/kg/h), or cocaine (0.1-0.32 mg/kg/h). Results During saline treatment, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Continuous 7-day treatments with d-amphetamine, methylphenidate or cocaine did not significantly attenuate methamphetamine vs. food choice up to doses that decreased rates of operant responding. However, 0.1 mg/kg/h d-amphetamine did eliminate methamphetamine choice in two monkeys. Conclusions The present subchronic treatment resultssupport the utility of preclinical methamphetamine choice to evaluate candidate medications for methamphetamine addiction. Furthermore, these results confirm and extend previous results demonstrating differential pharmacological mechanisms between cocaine choice and methamphetamine choice. PMID:26361713

  11. Use of barusiban in a novel study design for evaluation of tocolytic agents in pregnant and neonatal monkeys, including behavioural and immunological endpoints

    DEFF Research Database (Denmark)

    Rasmussen, Allan D; Nelson, Joyce K; Chellman, Gary J

    2007-01-01

    The oxytocin receptor antagonist barusiban, currently being developed for treatment of preterm labour, was investigated in pregnant cynomolgus monkeys with a 9-month postnatal follow-up of their offspring. The nature of barusiban, its indication, and the potential exposure of pre- and postnatal...

  12. Autoradiographic Mapping of 5-HT(1B/1D) Binding Sites in the Rhesus Monkey Brain Using [carbonyl-C]zolmitriptan.

    Science.gov (United States)

    Lindhe, Orjan; Almqvist, Per; Kågedal, Matts; Gustafsson, Sven-Åke; Bergström, Mats; Nilsson, Dag; Antoni, Gunnar

    2011-01-01

    Zolmitriptan is a serotonin 5-HT(1B/1D) receptor agonist that is an effective and well-tolerated drug for migraine treatment. In a human positron emission tomography study, [(11)C]zolmitriptan crossed the blood-brain barrier but no clear pattern of regional uptake was discernable. The objective of this study was to map the binding of [(11)C]zolmitriptan in Rhesus monkey brain using whole hemisphere in vitro autoradiography with [(11)C]zolmitriptan as a radioligand. In saturation studies, [(11)C]zolmitriptan showed specific (90%) binding to a population of high-affinity binding sites (Kd 0.95-5.06 nM). There was regional distribution of binding sites with the highest density in the ventral pallidum, followed by the external globus pallidus, substantia nigra, visual cortex, and nucleus accumbens. In competitive binding studies with 5-HT(1) receptor antagonists, [(11)C]zolmitriptan binding was blocked by selective 5-HT(1B) and 5-HT(1D) ligands in all target areas. There was no appreciable change in binding with the addition of a 5-HT(1A) receptor antagonist.

  13. Autoradiographic Mapping of 5-H T 1B/1D Binding Sites in the Rhesus Monkey Brain Using [carbonyl-11C]zolmitriptan

    Science.gov (United States)

    Lindhe, Örjan; Almqvist, Per; Kågedal, Matts; Gustafsson, Sven-Åke; Bergström, Mats; Nilsson, Dag; Antoni, Gunnar

    2011-01-01

    Zolmitriptan is a serotonin 5-HT1B/1D receptor agonist that is an effective and well-tolerated drug for migraine treatment. In a human positron emission tomography study, [11C]zolmitriptan crossed the blood-brain barrier but no clear pattern of regional uptake was discernable. The objective of this study was to map the binding of [11C]zolmitriptan in Rhesus monkey brain using whole hemisphere in vitro autoradiography with [11C]zolmitriptan as a radioligand. In saturation studies, [11C]zolmitriptan showed specific (90%) binding to a population of high-affinity binding sites (Kd 0.95–5.06 nM). There was regional distribution of binding sites with the highest density in the ventral pallidum, followed by the external globus pallidus, substantia nigra, visual cortex, and nucleus accumbens. In competitive binding studies with 5-HT1 receptor antagonists, [11C]zolmitriptan binding was blocked by selective 5-HT1B and 5-HT1D ligands in all target areas. There was no appreciable change in binding with the addition of a 5-HT1A receptor antagonist. PMID:22013519

  14. Autoradiographic Mapping of 5-HT1B/1D Binding Sites in the Rhesus Monkey Brain Using [carbonyl-11C]zolmitriptan

    Directory of Open Access Journals (Sweden)

    Örjan Lindhe

    2011-01-01

    Full Text Available Zolmitriptan is a serotonin 5-HT1B/1D receptor agonist that is an effective and well-tolerated drug for migraine treatment. In a human positron emission tomography study, [11C]zolmitriptan crossed the blood-brain barrier but no clear pattern of regional uptake was discernable. The objective of this study was to map the binding of [11C]zolmitriptan in Rhesus monkey brain using whole hemisphere in vitro autoradiography with [11C]zolmitriptan as a radioligand. In saturation studies, [11C]zolmitriptan showed specific (90% binding to a population of high-affinity binding sites (Kd 0.95–5.06 nM. There was regional distribution of binding sites with the highest density in the ventral pallidum, followed by the external globus pallidus, substantia nigra, visual cortex, and nucleus accumbens. In competitive binding studies with 5-HT1 receptor antagonists, [11C]zolmitriptan binding was blocked by selective 5-HT1B and 5-HT1D ligands in all target areas. There was no appreciable change in binding with the addition of a 5-HT1A receptor antagonist.

  15. Chemoprophylaxis with sporozoite immunization in P. knowlesi rhesus monkeys confers protection and elicits sporozoite-specific memory T cells in the liver

    Science.gov (United States)

    Spring, Michele D.; Yongvanitchit, Kosol; Kum-Arb, Utaiwan; Limsalakpetch, Amporn; Im-Erbsin, Rawiwan; Ubalee, Ratawan; Vanachayangkul, Pattaraporn; Remarque, Edmond J.; Angov, Evelina; Smith, Philip L.; Saunders, David L.

    2017-01-01

    Whole malaria sporozoite vaccine regimens are promising new strategies, and some candidates have demonstrated high rates of durable clinical protection associated with memory T cell responses. Little is known about the anatomical distribution of memory T cells following whole sporozoite vaccines, and immunization of nonhuman primates can be used as a relevant model for humans. We conducted a chemoprophylaxis with sporozoite (CPS) immunization in P. knowlesi rhesus monkeys and challenged via mosquito bites. Half of CPS immunized animals developed complete protection, with a marked delay in parasitemia demonstrated in the other half. Antibody responses to whole sporozoites, CSP, and AMA1, but not CelTOS were detected. Peripheral blood T cell responses to whole sporozoites, but not CSP and AMA1 peptides were observed. Unlike peripheral blood, there was a high frequency of sporozoite-specific memory T cells observed in the liver and bone marrow. Interestingly, sporozoite-specific CD4+ and CD8+ memory T cells in the liver highly expressed chemokine receptors CCR5 and CXCR6, both of which are known for liver sinusoid homing. The majority of liver sporozoite-specific memory T cells expressed CD69, a phenotypic marker of tissue-resident memory (TRM) cells, which are well positioned to rapidly control liver-stage infection. Vaccine strategies that aim to elicit large number of liver TRM cells may efficiently increase the efficacy and durability of response against pre-erythrocytic parasites. PMID:28182750

  16. Antinociceptive interactions between Mu-opioid receptor agonists and the serotonin uptake inhibitor clomipramine in rhesus monkeys: role of Mu agonist efficacy.

    Science.gov (United States)

    Banks, Matthew L; Rice, Kenner C; Negus, S Stevens

    2010-11-01

    Mu-opioid agonists are effective analgesics but have undesirable effects such as sedation and abuse liability that limit their clinical effectiveness. Serotonergic systems also modulate nociception, and serotonin uptake inhibitors may be useful as adjuncts to enhance analgesic effects and/or attenuate undesirable effects of mu agonists. This study examined the effects of the serotonin uptake inhibitor clomipramine on behavioral effects produced in rhesus monkeys by mu agonists with varying efficacy at mu receptors (nalbuphine morphine > methadone. In the assay of capsaicin-induced allodynia, nalbuphine produced dose-dependent antiallodynia. Clomipramine alone was inactive, but as in the assay of thermal nociception, it produced a proportion-dependent enhancement in the effects of nalbuphine. These findings suggest that serotonin uptake inhibitors can selectively enhance the antinociceptive effects of mu agonists in nonhuman primates. These effects of serotonin uptake inhibitors may depend on the proportion of the serotonin uptake inhibitor and the efficacy of the mu agonist. The greatest enhancement was observed with intermediate proportions of clomipramine in combination with the low-efficacy mu agonist nalbuphine.

  17. Saccade generation by the frontal eye fields in rhesus monkeys is separable from visual detection and bottom-up attention shift.

    Science.gov (United States)

    Lee, Kyoung-Min; Ahn, Kyung-Ha; Keller, Edward L

    2012-01-01

    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.

  18. Satratoxin-G from the black mold Stachybotrys chartarum induces rhinitis and apoptosis of olfactory sensory neurons in the nasal airways of rhesus monkeys.

    Science.gov (United States)

    Carey, Stephan A; Plopper, Charles G; Hyde, Dallas M; Islam, Zahidul; Pestka, James J; Harkema, Jack R

    2012-08-01

    Satratoxin-G (SG) is a trichothecene mycotoxin of Stachybotrys chartarum, the black mold suggested to contribute etiologically to illnesses associated with water-damaged buildings. We have reported that intranasal exposure to SG evokes apoptosis of olfactory sensory neurons (OSNs) and acute inflammation in the nose and brain of laboratory mice. To further assess the potential human risk of nasal airway injury and neurotoxicity, we developed a model of SG exposure in monkeys, whose nasal airways more closely resemble those of humans. Adult, male rhesus macaques received a single intranasal instillation of 20 µg SG (high dose, n = 3), or 5 µg SG daily for four days (repeated low dose, n = 3) in one nasal passage, and saline vehicle in the contralateral nasal passage. Nasal tissues were examined using light and electron microscopy and morphometric analysis. SG induced acute rhinitis, atrophy of the olfactory epithelium (OE), and apoptosis of OSNs in both groups. High-dose and repeated low-dose SG elicited a 13% and 66% reduction in OSN volume density, and a 14-fold and 24-fold increase in apoptotic cells of the OE, respectively. This model provides new insight into the potential risk of nasal airway injury and neurotoxicity caused by exposure to water-damaged buildings.

  19. 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.)

  20. Small changes in meal patterns lead to significant changes in total caloric intake. Effects of diet and social status on food intake in female rhesus monkeys.

    Science.gov (United States)

    Moore, Carla J; Lowe, Jonathan; Michopoulos, Vasiliki; Ulam, Patrick; Toufexis, Donna; Wilson, Mark E; Johnson, Zachary

    2013-03-01

    Social subordination in macaques is a well-established model to study the adverse effects of psychosocial stress on a number of health outcomes, including stress-induced eating. The present analysis was conducted to empirically define a meal among free-feeding female rhesus monkeys and to examine the roles of meal patterning (e.g., meal size, meal frequency, and snacking patterns) in findings from a previous study demonstrating that psychosocial stress increases overall caloric intake among subordinate animals with access to a highly palatable diet. Results indicate that all animals, regardless of social status, consumed more frequent meals, larger meals, and more calories in the form of snacks when a highly palatable diet was available. Additional findings suggest that subordinate animals consumed significantly larger meals compared to their dominant counterparts regardless of the dietary environment. Additionally, subordinate females with a history of exposure to the palatable diet consumed significantly more snack calories than both dominant and subordinate animals without previous exposure to the palatable diet when these females were returned to a standard laboratory diet. These findings illustrate how small changes in meal patterns can lead to significant increases in total caloric intake, which if prolonged, could promote the emergence of an obese phenotype. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. 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.

  2. 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.

  3. Distribution of GABA-ergic Neurons in the Rhesus Monkey Substantia Nigra%猕猴黑质GABA能神经元的分布

    Institute of Scientific and Technical Information of China (English)

    董大翠; 蔡秋云; 姚大卫; 陈活彝

    2000-01-01

    The higher evolutive rhesus monkeys were used as experimental materials. GABA-ergic neurons were observed under a light microscope. The GABA-ergic neurons in the pars reticulata of substantion nigra were numerous, dominant in the shape of polygonal or shuttle. The GABA neurons in the pars compacta of substantia nigra were less than in the pars reticulata, with the shape dominant in polygonal, round or shuttle.Many GABA-like positive fibres were observed at the inferior colliculus level of substantia nigra.%采用进化程度较高的灵长类动物猕猴作为实验材料,在光镜下观察黑质的GABA能神经元。在黑质网状部GABA能神经元数量多,以多角形和梭形为主,致密部的GABA能神经元较网状部略稀少,胞体形态以多角形、圆形和梭形为主;在下丘平面还可见到许多GABA样阳性神经纤维。

  4. Similarity in temperament between mother and offspring rhesus monkeys: sex differences and the role of monoamine oxidase-a and serotonin transporter promoter polymorphism genotypes.

    Science.gov (United States)

    Sullivan, Erin C; Mendoza, Sally P; Capitanio, John P

    2011-09-01

    Temperament is usually considered biologically based and largely inherited, however, the environment can shape the development of temperament. Allelic variation may confer differential sensitivity to early environment resulting in variations in temperament. Here we explore the relationship between measures of temperament in mothers and their first-born offspring and the role of genetic sensitivity in establishing the strength of these associations. Temperament ratings were conducted on 3- to 4-month-old rhesus monkeys after a 25-hr biobehavioral assessment. Factor analysis revealed a four-factor structure of temperament. Females assessed as infants have reproduced and their offspring have also been evaluated through the standardized testing paradigm. Canonical correlation analysis revealed statistically significant associations between factor scores of mothers and sons, but not mothers and daughters. Further, offspring possessing the high activity, "low risk," alleles of the rhMAOA-LPR or rh5-HTTLPR showed statistically significant canonical correlations, whereas those possessing other alleles did not, suggesting differential genetic sensitivity to the normative early experience of maternal temperament.

  5. 1,25-Dihydroxyvitamin D decreases HTRA1 promoter activity in the rhesus monkey--a plausible explanation for the influence of vitamin D on age-related macular degeneration?

    Science.gov (United States)

    Pahl, Lisa; Schubert, Stephanie; Skawran, Britta; Sandbothe, Maria; Schmidtke, Jörg; Stuhrmann, Manfred

    2013-11-01

    Age-related macular degeneration is the major cause of blindness in the elderly worldwide and the risk is influenced by both environmental and genetic risk factors. One important disease-associated region in humans is located on 10q26 and includes the two candidate genes ARMS2 and HTRA1. However, determination of the causative gene has not yet been possible and examining the situation in the rhesus monkey may help understand the situation in humans. In a recent paper, we characterized the rhesus monkey 10q26-orthologue region on chromosome 9 in detail and identified the drusen-associated HTRA1 promoter SNP rs196357513 as a putative risk factor. In this study, we predicted 9 binding sites for the vitamin D-dependent transcription factor vitamin D receptor in the rhesus HTRA1 promoter, one of which is destroyed by the rs196357513-risk allele. As patients with vitamin D deficit are at increased risk for age-related macular degeneration, a luciferase assay in transiently transfected ARPE19-cells was performed to evaluate the influence of the SNP rs196357513 and of 1,25-dihydroxyvitamin D on the rhesus monkey HTRA1 promoter activity. This revealed that the luciferase activity of the promoter construct containing the rs196357513 wild type allele was significantly reduced after vitamin D stimulation. An in silico analysis and literature search imply that this regulation could also play a role in human HTRA1 expression. Moreover, HTRA1 promoter activity of the construct containing the rs196357513 risk allele appeared diminished in comparison to the construct with the wild type allele, albeit this difference was not significant. The lower promoter activity due to the rhesus monkey rs196357513 risk allele apparently contradicts the common hypothesis for the human HTRA1 promoter risk allele of SNP rs11200638, for which a higher promoter activity has been observed. Our data point to a yet unexpected effect of decreased HTRA1 expression on drusen pathogenesis. Thus not only a

  6. 恒河猴和树鼩角膜内皮细胞的比较分析%Comparison of the corneal endothelial cells of rhesus monkeys and tree shrews

    Institute of Scientific and Technical Information of China (English)

    吴敏; 李娜; 孙晓梅; 胡竹林

    2016-01-01

    的合适实验动物。%Objective To analyze and compare the characteristics and differences of corneal endothelial cells of rhesus monkey and tree shrew eyes.Methods Corneal endothelial cells of 6 healthy rhesus monkeys (12 eyes) and 20 healthy tree shrews (40 eyes) were measured using a non-contact SP3000P specular microscope.Eight parameters were de-termined and compared with relevant parameters of human eyes reported in the literature, including minimum cell area (Smin), maximum cell area (Smax), average cell area (Savg), standard deviation of cell area (SD), coefficient of variabili-ty ( CV) , cell density ( CD) , hexagonality percentage ( HG%) and central corneal thickness ( CCT) .Results The ima-ging and measurement of all parameters could be completed in a short time both in rhesus monkeys and tree shrews.The time spent in the two kinds of animals was not significantly different.The CCT was ( 449.2 ±12.8 ) μm and ( 262.4 ± 24.6) μm, Smin was (120.4 ±26.3) S/μm2 and (153.2 ±42.9) S/μm2 , Smax was (705.0 ±130.8) S/μm2 and (468.7 ±109.3) S/μm2 , Savg was (351.1 ±26.1) and (295.4 ±18.9) S/μm2 , SSD was (113.1 ±27.4) and (75.9 ±27.3) S/μm2, CV was (31.9 ±6.0) and (25.3 ±8.3), CD was (2874.2 ±203.8) p/cell· mm-2 and (3399.3 ±224.7) p/cell· mm-2 , and the HG% was (58.6 ±9.1) and (94.0 ±9.7) in the rhesus monkeys andt tree shrews, respectively. The differences of all the above parameters between rhesus monkeys and tree shrews were statistically significant ( P<0.05 for all) .The cornea of tree shrews was significantly thinner than that of rhesus monkeys.The area and coefficient of varia-bility of tree shrews were smaller to those of rhesus monkeys, while the cell density and hexagonality percentage were higher than those of rhesus monkeys.Compared with human eyes, the CCT, CV and HG%in rhesus monkeys were highly simi-lar, while the CD was lower than that of human eyes.The CCT in tree shrew was only 60%of the rhesus monkey eyes and 50%of human eyes, while the CD and Savg

  7. Effects of ICOS+ T cell depletion via afucosylated monoclonal antibody MEDI-570 on pregnant cynomolgus monkeys and the developing offspring.

    Science.gov (United States)

    Nicholson, Simone M; Carlesso, Gianluca; Cheng, Lily I; Cook, Halie; DaCosta, Karma; Leininger, Joel; McKeever, Kathleen; Scott, Stephen Weasel; Taylor, Devon; Streicher, Katie; Eck, Steve; Reed, Molly; Faggioni, Raffaella; Herbst, Ronald; Dixit, Rakesh; Ryan, Patricia C

    2017-09-13

    MEDI-570 is a fully human afucosylated monoclonal antibody (MAb) against Inducible T-cell costimulator (ICOS), highly expressed on CD4+ T follicular helper (TFH) cells. Effects of MEDI-570 were evaluated in an enhanced pre-postnatal development toxicity (ePPND) study in cynomolgus monkeys. Administration to pregnant monkeys did not cause any abortifacient effects. Changes in hematology and peripheral blood T lymphocyte subsets in maternal animals and infants and the attenuated infant IgG immune response to keyhole limpet hemocyanin (KLH) were attributed to MEDI-570 pharmacology. Adverse findings included aggressive fibromatosis in one dam and two infant losses in the high dose group with anatomic pathology findings suggestive of atypical lymphoid hyperplasia. The margin of safety relative to the no observed adverse effect level (NOAEL) for the highest planned clinical dose in the Phase 1a study was 7. This study suggests that women of child bearing potential employ effective methods of contraception while being treated with MEDI-570. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. 恒河猴异体椎间盘移植组织学活性和生物化学研究%Study of histological viability and biochemical change of allografted intervertebral disc of rhesus monkey

    Institute of Scientific and Technical Information of China (English)

    周勇; 阮狄克; 陆瓞骥

    2002-01-01

    Objective To investigate the histological viability and the biochemical change of fresh allografted intervertebral disc of rhesus monkey.Methods Under general anaesthesia,osteotomies of 12 rhesus monkeys were made at the endplates about 2.0 mm away from the L4~ 5 intervertibral disc,then the fresh discs were transposed in two matched monkeys. The four groups of animals were sampled after the third, sixth,ninth and twelfth month respectively.Histological viability was assessed by 3H Proline incorporation and biochemical changes were measured by water,proteoglycan and collagen content. Results Study of histological viability demonstrated that the DPM (Disintegration Per Minute) of 3H Proline increased at the third month in anulus fibrous and the sixth month in nucleous pulposus.In the nucleus pulposus of implanted disc the study of biochemistry showed that proteoglycan content was not change obviously nine months ago, but proteoglycan content decreased at the twelfth month.Collagen contents increased at the third,sixth and ninth month. Water contents were not change among twelve months. In the annulus fibrous of implanted disc,proteoglycan and water contents decreased at the ninth month, but they were increased at the twelfth month. Collagen content increased at the sixth month,but it decreased at the ninth month again. Conclusions The present results showed the intervertibral disc grafted survived allologous transplantation.The fresh allografted intervertibral disc appeared some ability of regeneration.

  9. 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.

  10. Apparent Affinity Estimates and Reversal of the Effects of Synthetic Cannabinoids AM-2201, CP-47,497, JWH-122, and JWH-250 by Rimonabant in Rhesus Monkeys.

    Science.gov (United States)

    Hruba, Lenka; McMahon, Lance R

    2017-08-01

    Synthetic cannabinoids have been prohibited due to abuse liability and toxicity. Four such synthetic cannabinoids, AM-2201 ([1-(5-fluoropentyl)indol-3-yl]-naphthalen-1-ylmethanone), CP-47,497 (2-[(1R,3S)-3-hydroxycyclohexyl]-5-(2-methyloctan-2-yl)phenol), JWH-122 [(4-methylnaphthalen-1-yl)-(1-pentylindol-3-yl)methanone], and JWH-250 [2-(2-methoxyphenyl)-1-(1-pentylindol-3-yl)ethanone], were tested for their capacity to produce CB1 receptor-mediated discriminative stimulus effects in two groups of rhesus monkeys. One group (n = 4) discriminated Δ(9)-tetrahydrocannabinol (∆(9)-THC; 0.1 mg/kg i.v.), and a second group (n = 4) discriminated the cannabinoid antagonist rimonabant (1 mg/kg i.v.) while receiving 1 mg/kg/12 hours of ∆(9)-THC. AM-2201, JWH-122, CP-47,497, JWH-250, and ∆(9)-THC increased ∆(9)-THC lever responding. Duration of action was 1-2 hours for AM-2201, JWH-122, and JWH-250 and 4-5 hours for CP-47,497 and ∆(9)-THC. Rimonabant (1 mg/kg) surmountably antagonized the discriminative stimulus effects of all cannabinoid agonists; the magnitude of rightward shift was 10.6-fold for AM-2201, 10.7-fold for JWH-122, 11.0-fold for CP-47,497, and 15.7-fold for JWH-250. The respective pKB values were not significantly different: 6.61, 6.65, 6.66, and 6.83. In ∆(9)-THC-treated monkeys discriminating rimonabant, AM-2201 (0.1 and 0.32 mg/kg), JWH-122 (0.32 and 1 mg/kg), JWH-250 (1 and 3.2 mg/kg), and CP-47,497 (0.32, 1, and 3.2 mg/kg) produced not only rate-decreasing effects that were reversed by rimonabant, but also dose-dependent, rightward shifts in the rimonabant discrimination dose-effect function. These results show striking similarity in the CB1 receptor mechanism mediating the subjective effects of AM-2201, JWH-122, JWH-250, and CP-47,497. For products containing AM-2201 and JWH-122, a short duration of action could lead to more frequent use; moreover, inattention to differences in potency among synthetic cannabinoids could underlie unexpected

  11. Visual Evoked Potentials to Light Flashes in Captive Rhesus Monkeys: A Study Reflecting Cerebral Cortical Activity and Brain Maturation

    Directory of Open Access Journals (Sweden)

    S.A. Solís-Chávez

    2014-01-01

    Full Text Available Visual evoked potentials (VEPs are useful electrophysiological diagnostic tools for evaluating retinal response of the visual cortex and detecting its functional integrity in humans and animals. To analyze the VEPs and physiologic response of the visual pathway of a random population of captive-bred monkeys of the Macaca mulatta species throughout different physiologic stages after stimulation with stroboscopic light flashes. In this study we used 20 non-human primates (M. mulatta, 10 males and 10 females, divided into five age-dependant cohorts of 2 males and 2 females. Two replicable negative waveforms and one positive were recorded, as reliable indicators of electrical conductivity at specific anatomical nuclei of the visual pathways. Statistically significant differences were primarily observed in group 1 when compared against the remaining groups for the three evaluated waveforms. Waveform morphology characteristically presented steady deviations related to ontogenetic development of the studied population.

  12. 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.

  13. Temporal and spatial expression of MMP-2, -9, -14 and their inhibitors TIMP-1, -2, -3 in the corpus luteum of the cycling rhesus monkey

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The corpus luteum (CL) is a transient endocrine organ that secretes progesterone to support early pregnancy. If implantation is unsuccessful, luteolysis is initiated. Extensive tissue remodeling occurs during CL formation and luteolysis. In this study, we have studied the possible involvement of MMP-2, -9, -14, and their inhibitors, TIMP-1, -2, -3 in the CL of cycling rhesus monkey at various stages by in situ hybridization, immunohistochemistry and microscopic assessment. The results showed that the MMP-2 mRNA and protein were mainly expressed in the endothelial cells at the early and middle stages of the CL development, while their expressions were observed in the luteal cells at the late stage during luteal regression. MMP-9 protein was detected in the CL at the early and middle stages, and obviously increased at the late stage. The expressions of MMP-14 and TIMP-1 mRNA were high at the early and late stages, and low at the middle stage. TIMP-2 mRNA was high throughout all the stages, the highest level could be observed at the late stage. The TIMP-3 production was detected throughout all the stages, but obviously declined during CL regression. MMP-9, -14 and TIMP-1, -2, -3 were mainly localized in the cytoplasm of the steroidogenic cells. The results suggest that the MMP/TIMP system is involved in regulation of CL development in the primate, and the coordinated expression of MMP-2, -14 and TIMP-1, -3 may have a potential role in the CL formation and the functional maintaining, while the interaction of MMP-2, -9, -14 and TIMP-1, -2, -3 might also play a role in CL regression at the late stage of CL development in the primate.

  14. The discriminative stimulus effects of midazolam are resistant to modulation by morphine, amphetamine, dizocilpine and γ-butyrolactone in rhesus monkeys

    Science.gov (United States)

    Bai, Xiang; France, Charles P.; Gerak, Lisa R.

    2011-01-01

    Rationale Although abuse of benzodiazepines alone is uncommon, it is high in polydrug abusers, including those who abuse primarily opioids or stimulants. Objectives This study investigated whether drugs that are abused (e.g., amphetamine) or have mechanisms of action similar to abused drugs (e.g., morphine) alter the discriminative stimulus effects of the benzodiazepine midazolam. Methods Three rhesus monkeys discriminated 0.56 mg/kg of midazolam while responding under a fixed ratio 10 schedule of food presentation. Dose-effect curves were determined for midazolam alone and in the presence of morphine (opioid receptor agonist), amphetamine (dopamine receptor indirect agonist), dizocilpine (N-methyl-D-aspartic acid receptor antagonist), or γ-butyrolactone (prodrug of γ-hydroxybutyrate, which acts primarily at GABAB receptors). Results Doses of midazolam larger than 0.32 mg/kg produced ≥80% midazolam-lever responding. When administered alone, morphine, amphetamine, dizocilpine and γ-butyrolactone did not produce midazolam-lever responding, although large doses of each drug eliminated responding; when administered in combination with midazolam, they did not alter the discriminative stimulus effects of midazolam up to doses that markedly decreased response rates. Conclusions The current study demonstrates a lack of modulation of the discriminative stimulus effects of midazolam by morphine, amphetamine, dizocilpine, and γ-butyrolactone. Other effects of benzodiazepines, such as their reinforcing effects, might be altered by these other drugs, or benzodiazepines might modulate the discriminative stimulus or reinforcing effects of the other drugs, which might contribute to the relatively high incidence of benzodiazepine abuse among polydrug abusers. PMID:21503606

  15. Immunogenicity of a meningococcal native outer membrane vesicle vaccine with attenuated endotoxin and over-expressed factor H binding protein in infant rhesus monkeys.

    Science.gov (United States)

    Koeberling, Oliver; Seubert, Anja; Santos, George; Colaprico, Annalisa; Ugozzoli, Mildred; Donnelly, John; Granoff, Dan M

    2011-06-24

    We previously investigated immunogenicity of meningococcal native outer membrane vesicle (NOMV) vaccines prepared from recombinant strains with attenuated endotoxin (ΔLpxL1) and over-expressed factor H binding protein (fHbp) in a mouse model. The vaccines elicited broad serum bactericidal antibody responses. While human toll-like receptor 4 (TLR-4) is mainly stimulated by wildtype meningococcal endotoxin, mouse TLR-4 is stimulated by both the wildtype and mutant endotoxin. An adjuvant effect in mice of the mutant endotoxin would be expected to be much less in humans, and may have contributed to the broad mouse bactericidal responses. Here we show that as previously reported for humans, rhesus primate peripheral blood mononuclear cells incubated with a NOMV vaccine from ΔLpxL1 recombinant strains had lower proinflammatory cytokine responses than with a control wildtype NOMV vaccine. The cytokine responses to the mutant vaccine were similar to those elicited by a detergent-treated, wildtype outer membrane vesicle vaccine that had been safely administered to humans. Monkeys (N=4) were immunized beginning at ages 2-3 months with three doses of a NOMV vaccine prepared from ΔLpxL1 recombinant strains with over-expressed fHbp in the variant 1 and 2 groups. The mutant NOMV vaccine elicited serum bactericidal titers≥1:4 against all 10 genetically diverse strains tested, including 9 with heterologous PorA to those in the vaccine. Negative-control animals had serum bactericidal titers<1:4. Thus, the mutant NOMV vaccine elicited broadly protective serum antibodies in a non-human infant primate model that is more relevant for predicting human antibody responses than mice. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. 赛米司酮或米非司酮经口给药终止猕猴早孕有效剂量的研究%Study on the effective doses of samistone and mifepristone in terminating early pregnancy of rhesus monkeys by oral administration

    Institute of Scientific and Technical Information of China (English)

    王卫芳; 张美云; 廖爱华; 左明达; 庞雪冰; 朱继望; 周慧; 常翠芳; 张翠群; 伏晓敏; 金爱华

    2012-01-01

    Objective: To observe the effect of samistone on terminating early pregnancy of rhesus monkeys and its impact on the a-mount of vaginal bleeding, provide an experimental basis for researching and developing new drugs. Methods: The pregnant rhesus monkeys were randomly divided into seven groups: the rhesus monkeys in samistone group and mifepristone group were divided into low - dose group, middle -dose group, and high -dose group (5 mg ? Kg-1 ? D-1, 10 mg ? Kg-1 ? D-1, and 15 mg ? Kg-1 ? D-1), respectively; excipient (0.5% sodium carboxymethylcellulose) group was designed, five rhesus monkeys in each group. The rhesus monkeys in samistone group and mifepristone group were treated with different doses of samistone and mifepristone in a fasting state on the 42nd -48th day during menstrual cycle, once a day for three days, 200 μg misoprostol was administrated on the fourth day; the adverse reactions were observed after treatment, B ultrasound was applied to predict abortion and development of embryos on the fifteenth day. Results: The complete abortion rates in high - dose samistone group and middle - dose samistone group were 60.00% (3/5) and 20.00% (1 /5), respectively; while in low - dose samistone group, no abortion occurred. The complete abortion rates in high - dose mifeprislone group, middle - dose mifepristone group, and low - dose mifepristone group were 80. 00% (4/5 ) , 40.00% (2/5 ) , and 20.00% ( 1/5), respectively. The total abortion rates in samistone group and mifepristone group were 26. 67% (4/15) and 46.67% (7/15), there was no statistically significant difference between the two groups (P > 0.05) . The duration time of vaginal bleeding in samistone group was significantly shorter than that in mifepristone group, the amount of vaginal bleeding in samistone group was significantly less than that in mifepristone group (P <0. 05) . Conclusion: Samistone can terminate early pregnancy of rhesus monkeys, shorten the bleeding time, and reduce the amount of

  17. Embryotoxicity of arsenite and arsenate. Distribution in pregnant mice and monkeys and effects on embryonic cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Lindgren, A.; Danielsson, R.G.; Dencker, L. (Department of Toxicology, Biomedical Center, Uppsala University, Sweden); Vahter, M. (National Institute of Environmental Medicine, Stockholm, Sweden)

    1984-01-01

    The distribution of /sup 74/As-labelled and arsenite in pregnant mice and a monkey has been studied by autoradiography and gamma counting of isolated tissues, and their in vitro toxicity to a chondrogenic system has been investigated. With both arsenic forms, given as single intravenous injections to the mother, the /sup 74/As-arsenic appeared to pass the mouse placenta relatively freely and approximately to the same extent. The retention time in material tissues including the placenta was, however, around three times longer with arsenite than with arsenate. In early gestation, high activity was registered in the embryonic neuroepithelium, which correlates well with reported CNS malformations in rodents. In late gestation, the distribution pattern was more like that in the adults. Accumulation in skin and squamous epithelia of the upper gastrointestinal tract (oral cavity, oesophagus and oesophageal region of stomach) dominated the distribution picture, especially at a long survival interval. Arsenate, but not arsenite, showed affinity for the calcified areas of the skeleton. A marmoset monkey in late gestation receiving arsenite showed a somewhat lower rate of placental transfer than the mice. Skin and liver had the highest concentrations (at 8 hrs), both in mother and foetuses. This species is known not to methylate arsenic, resulting in stronger binding and longer retention times of arsenic as compared with other species. The stronger binding in maternal tissues may possibly explain the lower rate of placental transfer. Arsenite was shown to inhibit cartilage formation in a chick limb bud mesenchymal spot culture system (ED50 approximately 5-10..mu..M) while arsenate seemed to be without effect at concentrations up to 200 ..mu..M (highest tested). Arsenate, however, showed a potential of the arsenite toxicity.

  18. Embryotoxicity of arsenite and arsenate. Distribution in pregnant mice and monkeys and effects on embryonic cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Lindgren, A.; Danielsson, R.G.; Dencker, L. (Department of Toxicology, Biomedical Center, Uppsala University, Sweden); Vahter, M. (National Institute of Environmental Medicine, Stockholm, Sweden)

    1984-01-01

    The distribution of /sup 74/As-labelled arsenate and arsenite in pregnant mice and a monkey has been studied by autoradiography and gamma counting of isolated tissues, and their in vitro toxicity to a chondrogenic system has been investigated. With both arsenic forms, given as single intravenous injections to the mother, the /sup 74/As-arsenic appeared to pass the mouse placenta relatively freely and approximately to the same extent. The retention time in material tissues including the placenta was, however, around three times longer with arsenite than with arsenate. In early gestation, high activity was registered in the embryonic neuroepithelium, which correlates well with reported CNS malformations in rodents. In late gestation, the distribution pattern was more like that in the adults. Accumulation in skin and squamous epithelia of the upper gastrointestinal tract (oral cavity, oesophagus and oesophageal region of stomach) dominated the distribution pucture, especially at a long survival interval. Arsenate, but not arsenite, showed affinity for the calcified areas of the skeleton. A marmoset monkey in late gestation receiving arsenite showed a somewhat lower rate of placental transfer than the mice. Skin and liver had the highest concentrations (at 8 hrs), both in mother and foetuses. This species is known not to methylate arsenic, resulting in stronger binding and longer retention times of arsenic as compared with other species. The stronger binding in maternal tissues may possibly explain the lower rate of placental transfer. Arsenite was shown to inhibit cartilage formation in a chick limb bud mesenchymal spot culture system (ED50 approximately 5-10..mu..M) while arsenate seemed to be without effect at concentrations up to 200 ..mu..M (highest tested). Arsenate, however, showed a potential of the arsenite toxicity.

  19. Short-term administration of antivascular endothelial growth factor antibody in the late follicular phase delays follicular development in the rhesus monkey.

    Science.gov (United States)

    Zimmermann, R C; Xiao, E; Husami, N; Sauer, M V; Lobo, R; Kitajewski, J; Ferin, M

    2001-02-01

    Indirect evidence in the nonhuman primate and human suggests that angiogenesis and regulators of angiogenesis such as vascular endothelial growth factor (VEGF) may play an active role in cyclic folliculogenesis. Indeed, the follicle selected for maturation and ovulation possesses a denser microvascular network, and VEGF messenger ribonucleic acid and its protein have been identified in granulosa cells of the developing follicle during the mid- and late follicular phases, with a more intense signal in the mature follicle. The objective of this study was to obtain direct evidence in the nonhuman primate for an active role of VEGF in follicular growth and maturation by studying the effect of VEGF-blocking antibodies in this process. After documenting two normal ovulatory cycles, female rhesus monkeys (n = 7) received iv injections of anti-VEGF antibodies (0.5 mg) twice on successive days in the late follicular phase. Three monkeys also received nonspecific goat IgG (0.5 mg) twice on successive days in the late follicular phase. Daily measurements of estradiol, progesterone, LH, and FSH were obtained during the two control cycles, the anti-VEGF treatment and posttreatment cycles, and the IgG treatment cycle. Anti-VEGF antibody administration significantly lengthened the follicular phase in six of seven monkeys to 17.8 +/- 1.7 vs. 10.0 +/- 0.7 and 9.8 +/- 0.6 in control cycles and 10.7 +/- 0.3 days (mean +/- SE) in IgG-treated cycles. The expected late follicular phase rise in estradiol, as documented in the control cycles (day 0, 96.1 +/- 6.0; day 1, 125.5 +/- 20.0; day 2, 165.5 +/- 24.9; day 3, 183.8 +/- 11.0 pg/mL), was interrupted by anti-VEGF antibody treatment (99.3 +/- 5.0, day 0, preinjection control) to 63.3 +/- 12.2 (day 1), 48.5 +/- 8.7 (day 2), and 57.6 +/- 9.0 (day 3). Mean FSH levels were significantly increased by day 2 of anti-VEGF antibody treatment. After a variable delay, estradiol concentrations increased to reach a preovulatory peak in all anti

  20. 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

  1. 3B11-N, a monoclonal antibody against MERS-CoV, reduces lung pathology in rhesus monkeys following intratracheal inoculation of MERS-CoV Jordan-n3/2012

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Reed F., E-mail: johnsonreed@mail.nih.gov [Emerging Viral Pathogens Section National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States); Bagci, Ulas [Center for Infectious Disease Imaging, National Institutes of Health Clinical Center, Bethesda MD 20892 (United States); Center for Research in Computer Vision (CRCV), Department of Electrics Electronics and Computer Science, University of Central Florida, Orlando, FL 32816, USA. (United States); Keith, Lauren [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States); Tang, Xianchun [Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215 (United States); Mollura, Daniel J. [Center for Infectious Disease Imaging, National Institutes of Health Clinical Center, Bethesda MD 20892 (United States); Zeitlin, Larry [Mapp Biopharmaceutical, Inc., San Diego CA 92121 (United States); Qin, Jing [Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Huzella, Louis; Bartos, Christopher J. [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States); Bohorova, Natasha; Bohorov, Ognian; Goodman, Charles; Kim, Do H.; Paulty, Michael H.; Velasco, Jesus; Whaley, Kevin J. [Mapp Biopharmaceutical, Inc., San Diego CA 92121 (United States); Johnson, Joshua C.; Pettitt, James; Ork, Britini L. [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States); Solomon, Jeffrey [Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research,Frederick, MD 21702-USA. (United States); and others

    2016-03-15

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was identified in 2012 as the causative agent of a severe, lethal respiratory disease occurring across several countries in the Middle East. To date there have been over 1600 laboratory confirmed cases of MERS-CoV in 26 countries with a case fatality rate of 36%. Given the endemic region, it is possible that MERS-CoV could spread during the annual Hajj pilgrimage, necessitating countermeasure development. In this report, we describe the clinical and radiographic changes of rhesus monkeys following infection with 5×10{sup 6} PFU MERS-CoV Jordan-n3/2012. Two groups of NHPs were treated with either a human anti-MERS monoclonal antibody 3B11-N or E410-N, an anti-HIV antibody. MERS-CoV Jordan-n3/2012 infection resulted in quantifiable changes by computed tomography, but limited other clinical signs of disease. 3B11-N treated subjects developed significantly reduced lung pathology when compared to infected, untreated subjects, indicating that this antibody may be a suitable MERS-CoV treatment. - Highlights: • MERS-CoV Jordan-n3/2012 challenge of rhesus monkeys results in a mild disease. • CT can be used to monitor disease progression to aid models of human disease. • Treatment with the human monoclonal antibody 3B11-N resulted in decreased disease.

  2. 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.

  3. Quantitative Analyses of Antagonism: Combinations of Midazolam and Either Flunitrazepam or Pregnanolone in Rhesus Monkeys Discriminating Midazolam

    Science.gov (United States)

    France, Charles P.

    2012-01-01

    Adverse effects of benzodiazepines limit their clinical use; these effects might be reduced without altering therapeutic effects by administering other positive GABAA modulators (i.e., neuroactive steroids) with benzodiazepines. One concern with this strategy involves reversing these combined effects in case of overdose. The current study examined whether flumazenil can attenuate the combined effects of two benzodiazepines, midazolam and flunitrazepam, and the combined effects of midazolam and the neuroactive steroid pregnanolone, in four monkeys discriminating midazolam. Each positive modulator produced ≥80% midazolam-lever responding. Interactions between midazolam and either flunitrazepam or pregnanolone were additive. Flumazenil antagonized the benzodiazepines when they were administered alone or in combination. Schild analyses yielded slopes that did not deviate from unity, regardless of whether benzodiazepines were administered alone or together; the pA2 value for flumazenil was 7.58. In contrast, flumazenil enhanced the effects of pregnanolone with 0.32 mg/kg flumazenil shifting the pregnanolone dose-effect curve 2-fold leftward. Flumazenil attenuated the combined effects of midazolam and pregnanolone, although antagonism was not dose-dependent. Thus, the interaction between two benzodiazepines was similar to that of a benzodiazepine and a neuroactive steroid; however, flumazenil more efficiently attenuated a combination of two benzodiazepines compared with a combination of a benzodiazepine and a neuroactive steroid. Although the magnitude of antagonism of a benzodiazepine combined with a neuroactive steroid was reduced, these results support continued exploration of the use of combinations of positive modulators to enhance therapeutic effects while reducing adverse effects. PMID:22173893

  4. Uterine EMG spectral analysis and relationship to mechanical activity in pregnant monkeys.

    Science.gov (United States)

    Mansour, S; Devedeux, D; Germain, G; Marque, C; Duchêne, J

    1996-03-01

    The objective is to analyse internal and external recordings of uterine EMG in order to reveal common features and to assess the relationship between electrical activity and intra-uterine pressure modification. Three monkeys participated in the study, one as a reference and the others for data. EMGs are recorded simultaneously, internally by unipolar wire electrodes and externally by bipolar Ag/AgCl electrodes. Intra-uterine pressure is recorded as a mechanical index. Except for delay measurements, parameters are derived from spectral analysis and relationships between recordings are assessed by studying the coherence. Spectral analysis exhibits two basic activities in the analysed frequency band, and frequency limits are defined as relevant parameters for electrical activity description. Parameter values do not depend on the internal electrode location. Internal and external EMGs present a similar spectral shape, despite differences in electrode configuration and tissue filtering. It is deduced that external uterine EMG is a good image of the genuine uterine electrical activity. To some extent, it can be related to an average cellular electrical activity.

  5. Increased levels of the acetaldehyde-derived DNA adduct N 2-ethyldeoxyguanosine in oral mucosa DNA from Rhesus monkeys exposed to alcohol.

    Science.gov (United States)

    Balbo, Silvia; Juanes, Rita Cervera; Khariwala, Samir; Baker, Erich J; Daunais, James B; Grant, Kathleen A

    2016-09-01

    Alcohol is a human carcinogen. A causal link has been established between alcohol drinking and cancers of the upper aerodigestive tract, colon, liver and breast. Despite this established association, the underlying mechanisms of alcohol-induced carcinogenesis remain unclear. Various mechanisms may come into play depending on the type of cancer; however, convincing evidence supports the concept that ethanol's major metabolite acetaldehyde may play a major role. Acetaldehyde can react with DNA forming adducts which can serve as biomarkers of carcinogen exposure and potentially of cancer risk. The major DNA adduct formed from this reaction is N (2)-ethylidenedeoxyguanosine, which can be quantified as its reduced form N (2)-ethyl-dG by LC-ESI-MS/MS. To investigate the potential use of N (2)-ethyl-dG as a biomarker of alcohol-induced DNA damage, we quantified this adduct in DNA from the oral, oesophageal and mammary gland tissues from rhesus monkeys exposed to alcohol drinking over their lifetimes and compared it to controls. N (2)-Ethyl-dG levels were significantly higher in the oral mucosa DNA of the exposed animals. Levels of the DNA adduct measured in the oesophageal mucosa of exposed animals were not significantly different from controls. A correlation between the levels measured in the oral and oesophageal DNA, however, was observed, suggesting a common source of formation of the DNA adducts. N (2) -Ethyl-dG was measured in mammary gland DNA from a small cohort of female animals, but no difference was observed between exposed animals and controls. These results support the hypothesis that acetaldehyde induces DNA damage in the oral mucosa of alcohol-exposed animals and that it may play role in the alcohol-induced carcinogenic process. The decrease of N (2)-ethyl-dG levels in exposed tissues further removed from the mouth also suggests a role of alcohol metabolism in the oral cavity, which may be considered separately from ethanol liver metabolism in the

  6. No effects of dioxin singly on limb malformations in macaque monkeys through epidemiological and treated studies

    Energy Technology Data Exchange (ETDEWEB)

    Asaoka, Kazuo; Iida, Hiroko [Kyoto Univ. (Japan). Primate Research Insitute, Dept. of Molecular and Cellular Biochemistry; Watanabe, Kunio [Kyoto Univ. (Japan). Primate Research Institute, Field Research Center; Goda, Hiroshi [Towa Kagaku Co., Ltd. (Japan); Ihara, Toshio; Nagata, Ryoichi [Shin Nippon Biomedical Laboratories, Ltd. (Japan). Safety Research Facility; Yasuda, Mineo [Hiroshima International Univ. (Japan). Fac. of Health Sciences, Dept. of Clinical Engineering; Kubata, Shunichiro [Tokyo Univ. (Japan). Dept. of Life Science, Graduate School of Arts and Sciences

    2004-09-15

    Human populations exposed with highly dioxin were suspected to be caused immunological dysfunctions, carcinogenesis, and developmental and reproductive dysfunctions. Because of species resemblances, the dioxin effects have been investigating using monkeys as a model for assessment of dioxin exposure on human health. Since 1957 the limb malformations of monkeys in Japan have been reported. The higher frequency of them was found in provisional groups of monkeys who were given the same kind of food for human. The chromosomal abnormalities are excluded from the factor for the congenital limb malformations that are still producing in Japan. In this study, the relations between dioxin and the limb malformations of macaque monkeys were estimated by the epidemiological and administered researches. The dioxin levels in monkeys were measured at two districts that one has the provisional groups including monkeys with limb malformations and the other has breeding groups never seeing the malformations for a long time. TEQ was calculated by the levels of dioxin isomers in the monkeys and the values show no difference between the two places and between the individuals with and without the limb malformations. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was administered via subcutaneous to pregnant rhesus monkeys from the day 20 of gestation to the day 90 after birth. The exposed babies, including the offspring and died in neonatal, had observed normal limbs in the range of 30-300 ng TCDD /kg of body weight.

  7. 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.

  8. Comparative proteomic analyses of the parietal lobe from rhesus monkeys fed a high-fat/sugar diet with and without resveratrol supplementation, relative to a healthy diet: Insights into the roles of unhealthy diets and resveratrol on function.

    Science.gov (United States)

    Swomley, Aaron M; Triplett, Judy C; Keeney, Jeriel T; Warrier, Govind; Pearson, Kevin J; Mattison, Julie A; de Cabo, Rafael; Cai, Jian; Klein, Jon B; Butterfield, D Allan

    2017-01-01

    A diet consisting of a high intake of saturated fat and refined sugars is characteristic of a Western-diet and has been shown to have a substantial negative effect on human health. Expression proteomics were used to investigate changes to the parietal lobe proteome of rhesus monkeys consuming either a high fat and sugar (HFS) diet, a HFS diet supplemented with resveratrol (HFS+RSV), or a healthy control diet for 2 years. Here we discuss the modifications in the levels of 12 specific proteins involved in various cellular systems including metabolism, neurotransmission, structural integrity, and general cellular signaling following a nutritional intervention. Our results contribute to a better understanding of the mechanisms by which resveratrol functions through the up- or down-regulation of proteins in different cellular sub-systems to affect the overall health of the brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. A technique of rhesus monkey neural progenitor cells intravitreal transplant to rats%在大鼠玻璃体内移植猕猴神经前体细胞的方法探索

    Institute of Scientific and Technical Information of China (English)

    边慧; 范耀东; 郭立云; 余化霖

    2012-01-01

    探索一种简单、可行的异种神经前体细胞眼内移植方法.采用机械性损伤方法造成大鼠视网膜局部受损,然后在损伤眼及对照眼玻璃体内移植绿色荧光蛋白(green fluorescence protein,GFP)标记的猕猴神经前体细胞,观察细胞能否存活.结果显示:经激光共聚焦显微镜检查发现移植细胞在损伤眼及对照眼内均可存活并整合至损伤眼视网膜.实验表明,玻璃体内异种移植GFP标记的猕猴神经前体细胞可以存活并整合,是一种可行的移植方法.%To investigate a simple and effective intraocular xenotransplant technique of rhesus monkey neural progenitor cells to rats, mechanical injury was induced in the rat's right retina. And the GFP-labeled rhesus monkey neural progenitor cells suspension was slowly injected into the vitreous space of the right injured and left control eye. Confocal image suggested that the xenografted cells survived in both the injured and control eye, meanwhile the cells integrated in the injured right retina. The results demonstrated that intravitreal xenotransplant could be adopted as a simple and reliable method.

  10. Culture and identification of the chondrocytes from auricular cartilage of rhesus monkey%猕猴耳廓软骨细胞的体外培养与鉴定

    Institute of Scientific and Technical Information of China (English)

    张金宁; 王旭东; 杨驰

    2001-01-01

    Objective:To culture the auricular chondrocytes of rhesus monkeyin vitro,and to certify the possibility of auricular cartilage as an ideal donor site for chondrocytes transplantation.Methods:The auricular cartilages of 6 rhesus monkeys were dissected and digested,the chondrocytes were isolated and cultured in F-12 medium.The changes of cellular morphology were investigated with inverted microscope.The cellular activities were studied with immunohistochemistry(IHC).Results:The homogenous,high-activity chondrocytes were harvested and cultured iv vitro successfully and IHC showed that there was no significant difference between type Ⅰ and type Ⅱ collagen stain in 3rd generation.Conclusions:Auricular cartilage of rhesus monkey is an ideal donor site for chondrocytes transplantation.%目的 掌握猕猴耳廓软骨细胞的体外分离、培养和鉴定技术,探讨耳廓软骨作为软骨细胞供区的可行性。材料与方法:对6只猕猴进行耳廓软骨取材、软骨细胞的分离,并行单层贴壁培养。通过倒置显微镜观察细胞生长情况并行细胞生长曲线的绘制;通过免疫组织化学染色对细胞分泌的基质成分进行鉴定。结果:6只猕猴的耳廓软骨经分离后,获得了高纯度、高活性的软骨细胞,并成功地进行了体外培养;软骨细胞倍增时间为98小时;免疫组织化学染色发现体外培养的软骨细胞具有分泌胶原基质的能力,但第三代细胞分泌Ⅰ、Ⅱ型胶原的能力无明显区别。结论:利用猕猴耳廓软骨细胞体外分离及培养,能成功地获得具有体内活性的软骨细胞,耳廓软骨是一种易获取的软骨细胞供区。

  11. X-ray CT imaging of normal abdominal and pelvic organs of adult rhesus monkeys%猕猴腹部及盆腔结构的CT影像学观察

    Institute of Scientific and Technical Information of China (English)

    周建华; 范春梅; 李志雄; 俞春英; 王训立

    2012-01-01

    Objective To obtain X-ray computed tomography (CT) imaging of abdominal and pelvic organs of healthy adult rhesus monkeys. Methods Six conventional laboratory rhesus monkeys, 3 male and 3 female, in the age of 5-8 yean were included in this study. The monkeys were placed on the CT table-board in supine position and were scanned to get CT images of the abdominal and pelvic organs by enhanced scan techniques. Volumetric data were collected and reconstruction of the original data was conducted. Meaningful anatomical scanning images were observed, identified and selected; 7 images of the abdominal structures and 10 pelvic organs (5 of males and 5 of females), and each layer of the major visceral organs were labeled. Result On the CT images, the subtle changes of most organs and tissues could be distinguished, and the interface of relatively large organs and blood vessels was clear. But the interface of smaller organs, blood vessels, nerves and muscles, etc. Was not distinct. Conclusions CT images of normal abdominal and pelvic structures of healthy adult rhesus monkeys has been obtained in this study. It provides valuable imaging basis for further studies on disease diagnosis and scientific experiments.%目的 应用CT技术对成年猕猴进行断层扫描,建立猕猴腹部及盆腔CT断层扫描图谱.方法 选择普通级实验猕猴6只,雌雄各半,年龄5~8岁,取头前尾后仰卧位,采用增强扫描CT技术,对其腹部及盆腔进行断层扫描,采集容积数据及对原始数据重建.通过观察、确认,精选具有解剖意义的扫描图像:腹部7张、盆腔10张(雌雄各5张),对其每个层面的主要脏器进行标注.结果 CT影像能分辨出大部分组织器官的细微变化,较大器官、大血管界面清晰,但较小器官和细小血管、神经、肌肉组织等界面尚不清晰.结论 获得了健康成年猕猴腹部及盆腔的影像学图谱,为CT技术在猕猴影像学研究、疾病的临床诊断及科学实验方面

  12. The distribution of substance P and kisspeptin in the mediobasal hypothalamus of the male rhesus monkey and a comparison of intravenous administration of these peptides to release GnRH as reflected by LH secretion

    Science.gov (United States)

    Kalil, Bruna; Ramaswamy, Suresh; Plant, Tony M.

    2016-01-01

    Substance P (SP) was recently reported to be expressed in human KNDy neurons and to enhance KNDy neuron excitability in the mouse hypothalamus. We therefore examined 1) interactions of SP and kisspeptin in the mediobasal hypothalamus of adult male rhesus monkeys using immunofluorescence, and 2) the ability of SP to induce LH release in GnRH primed, agonadal juvenile male monkeys. SP cell bodies were observed only occasionally in the arcuate nucleus (Arc), but more frequently dorsal to the Arc in the region of the pre-mammilary nucleus. Castration resulted in an increase in the number of SP cell bodies in the Arc but not in the other nuclei. SP fibers innervated the Arc where they were found in close apposition with kisspeptin perikarya in the periphery of this nucleus. Beaded SP axons projected to the median eminence where they terminated in the external layer and intermingled with beaded kisspeptin axons. Colocalization of the two peptides, however, was not observed. Although close apposition between SP fibers and kisspeptin neurons suggest a role for SP in modulating GnRH pulse generator activity, iv injections of SP failed to elicit release of GnRH (as reflected by LH) in the juvenile monkey. Although the finding of structural interactions between SP and kisspeptin neurons are consistent with the notion that this tachykinin may be involved in regulating pulsatile GnRH release, the apparent absence of expression of SP in KNDy neurons suggests that this peptide is unlikely to be a fundamental component of the primate GnRH pulse generator. PMID:26580201

  13. Effects of buspirone and the dopamine D3 receptor compound PG619 on cocaine and methamphetamine self-administration in rhesus monkeys using a food-drug choice paradigm.

    Science.gov (United States)

    John, William S; Banala, Ashwini K; Newman, Amy H; Nader, Michael A

    2015-04-01

    The dopamine (DA) D2 and D3 receptors have been associated with cocaine abuse. A recent study with the D3 receptor (D3R) partial agonist PG619 found that it attenuated cocaine-induced reinstatement and the D2-like receptor antagonist buspirone has shown positive outcomes in two studies of cocaine abuse in monkeys. However, a recent clinical trial indicated that buspirone did not improve abstinence in treatment-seeking cocaine abusers. The objective of the study was to examine PG619 and buspirone under a food-drug choice paradigm in order to better model the clinical findings. In addition, we extended the characterization of both compounds to include methamphetamine (MA) self-administration (SA). Six adult male rhesus monkeys were trained to respond under a concurrent food (1.0-g pellets) and drug (0.01-0.3 mg/kg/injection cocaine or MA) choice paradigm in which complete SA dose-response curves were determined each session (N = 3/group). Monkeys received 5 days of treatment with either PG619 (0.1-3.0 mg/kg, i.v.) or buspirone (0.01-1.0 mg/kg, i.m.). In a follow-up study, the SA doses were reduced (0.003-0.1 mg/kg/injection) to increase reinforcement frequency and buspirone was retested. PG619 did not affect cocaine or MA choice, while buspirone increased low-dose cocaine choice. Changing the SA doses increased the number of reinforcers received each session, but buspirone did not decrease drug choice. Consistent with clinical findings, these results do not support the use of buspirone for psychostimulant abuse and suggest that food-drug choice paradigms may have greater predictive validity than the use of other schedules of reinforcement.

  14. 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...

  15. Preclinical Assessment of Lisdexamfetamine as an Agonist Medication Candidate for Cocaine Addiction: Effects in Rhesus Monkeys Trained to Discriminate Cocaine or to Self-Administer Cocaine in a Cocaine Versus Food Choice Procedure.

    Science.gov (United States)

    Banks, Matthew L; Hutsell, Blake A; Blough, Bruce E; Poklis, Justin L; Negus, S Stevens

    2015-01-24

    Chronic amphetamine treatment decreases cocaine consumption in preclinical and human laboratory studies and in clinical trials. Lisdexamfetamine is an amphetamine prodrug in which L-lysine is conjugated to the terminal nitrogen of d-amphetamine. Prodrugs may be advantageous relative to their active metabolites due to slower onsets and longer durations of action; however, lisdexamfetamine treatment's efficacy in decreasing cocaine consumption is unknown. This study compared lisdexamfetamine and d-amphetamine effects in rhesus monkeys using two behavioral procedures: (1) a cocaine discrimination procedure (training dose = 0.32mg/kg cocaine, i.m.); and (2) a cocaine-versus-food choice self-administration procedure. In the cocaine-discrimination procedure, lisdexamfetamine (0.32-3.2mg/kg, i.m.) substituted for cocaine with lower potency, slower onset, and longer duration of action than d-amphetamine (0.032-0.32mg/kg, i.m.). Consistent with the function of lisdexamfetamine as an inactive prodrug for amphetamine, the time course of lisdexamfetamine effects was related to d-amphetamine plasma levels by a counter-clockwise hysteresis loop. In the choice procedure, cocaine (0-0.1mg/kg/injection, i.v.) and food (1g banana-flavored pellets) were concurrently available, and cocaine maintained a dose-dependent increase in cocaine choice under baseline conditions. Treatment for 7 consecutive days with lisdexamfetamine (0.32-3.2mg/kg/day, i.m.) or d-amphetamine (0.032-0.1mg/kg/h, i.v.) produced similar dose-dependent rightward shifts in cocaine dose-effect curves and decreases in preference for 0.032mg/kg/injection cocaine. Lisdexamfetamine has a slower onset and longer duration of action than amphetamine but retains amphetamine's efficacy to reduce the choice of cocaine in rhesus monkeys. These results support further consideration of lisdexamfetamine as an agonist-based medication candidate for cocaine addiction. © The Author 2015. Published by Oxford University Press on

  16. Determinants of lipoprotein(a) assembly: a study of wild-type and mutant apolipoprotein(a) phenotypes isolated from human and rhesus monkey lipoprotein(a) under mild reductive conditions.

    Science.gov (United States)

    Edelstein, C; Mandala, M; Pfaffinger, D; Scanu, A M

    1995-12-19

    We previously observed that rhesus monkey lipoprotein(a) [Lp(a)], is lysine-binding defective (Lys-) and attributed this deficiency to the presence of Arg72 in the lysine-binding site (LBS) of kringle IV-10 of apolipoprotein(a) [apo(a)] [Scanu, A.M., Miles, L.A., Fless, G.M., Pfaffinger, D., Eisenbart, J., Jackson, E., Hoover-Plow, J.L., Brunck, T., & Plow, E.F. (1993) J. Clin. Invest. 91, 283-291]. We also identified human mutants having Arg72 instead of Trp72 (wild type) in the LBS of kringle IV-10 [Scanu, A M., Pfaffinger, D., lEE, J.C., & Hinman, J. (1994) Biochim. Biophys. Acta 1227, 41-45]. Unique to the human mutant phenotype were the very low levels of plasma Lp(a), suggesting structural differences between human and rhesus apo(a) and a possible divergent mode of Lp(a) assembly. In order to explore the possibility of a relationship between apo(a) LBS and Lp(a) assembly, we developed a novel method for isolating wild-type and mutant apo(a) phenotypes in a free form by subjecting each parent Lp(a) to mild reductive conditions using 2 mM dithioerythritol (DTE) and 100 mM of the lysine analogue, epsilon-aminocaproic acid (EACA). The application of this method to the study of wild-type and mutant apo(a) species showed that regardless of the source of Lp(a), i.e., positive lysine binding (Lys+) or negative lysine binding (Lys-), all of the isolated free apo(a)s were Lys+. Moreover, incubation of free apo(a)s with their autologous human or rhesus low-density lipoproteins (LDL) generated Lp(a) complexes which were structurally and functionally indistinguishable from their parent native Lp(a). In each instance, the reassembly process was inhibited by the presence of either EACA or proline. These two reagents had a minimal effect on either Lp(a) or reassembled Lp(a) [RLp(a)]. Free apo(a) bound to apoB100 of very low density lipoproteins (VLDL) to form a triglyceride-rich Lp(a). These results show that (1) both human and rhesus Lp(a) are amenable to dissassembly and

  17. Application of a beta microprobe for quantification of regional cerebral blood flow with {sup 15}O-water and PET in rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Seki, Chie; Okada, Hiroyuki; Mori, Shinsuke; Kakiuchi, Takeharu; Yoshikawa, Etsuji; Nishiyama, Shingo; Tsukada, Hideo; Yamashita, Takaji [Hamamatsu Photonics K.K., Shizuoka (Japan). Central Research Laboratory

    1998-02-01

    A beta microprobe was successfully applied to monitor arterial input function for quantification of regional cerebral blood flow (rCBF) in the monkey brain with {sup 15}O-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 (PaCO{sub 2}=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)

  18. Induction of multi-antigen multi-stage immune responses against Plasmodium falciparum in rhesus monkeys, in the absence of antigen interference, with heterologous DNA prime/poxvirus boost immunization.

    Science.gov (United States)

    Jiang, George; Charoenvit, Yupin; Moreno, Alberto; Baraceros, Maria F; Banania, Glenna; Richie, Nancy; Abot, Steve; Ganeshan, Harini; Fallarme, Victoria; Patterson, Noelle B; Geall, Andrew; Weiss, Walter R; Strobert, Elizabeth; Caro-Aquilar, Ivette; Lanar, David E; Saul, Allan; Martin, Laura B; Gowda, Kalpana; Morrissette, Craig R; Kaslow, David C; Carucci, Daniel J; Galinski, Mary R; Doolan, Denise L

    2007-10-09

    The present study has evaluated the immunogenicity of single or multiple Plasmodium falciparum (Pf) antigens administered in a DNA prime/poxvirus boost regimen with or without the poloxamer CRL1005 in rhesus monkeys. Animals were primed with PfCSP plasmid DNA or a mixture of PfCSP, PfSSP2/TRAP, PfLSA1, PfAMA1 and PfMSP1-42 (CSLAM) DNA vaccines in PBS or formulated with CRL1005, and subsequently boosted with ALVAC-Pf7, a canarypox virus expressing the CSLAM antigens. Cell-mediated immune responses were evaluated by IFN-gamma ELIspot and intracellular cytokine staining, using recombinant proteins and overlapping synthetic peptides. Antigen-specific and parasite-specific antibody responses were evaluated by ELISA and IFAT, respectively. Immune responses to all components of the multi-antigen mixture were demonstrated following immunization with either DNA/PBS or DNA/CRL1005, and no antigen interference was observed in animals receiving CSLAM as compared to PfCSP alone. These data support the down-selection of the CSLAM antigen combination. CRL1005 formulation had no apparent effect on vaccine-induced T cell or antibody responses, either before or after viral boost. In high responder monkeys, CD4+IL-2+ responses were more predominant than CD8+ T cell responses. Furthermore, CD8+ IFN-gamma responses were detected only in the presence of detectable CD4+ T cell responses. Overall, this study demonstrates the potential for multivalent Pf vaccines based on rational antigen selection and combination, and suggests that further formulation development to increase the immunogenicity of DNA encoded antigens is warranted.

  19. 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

  20. Comparison of the oxime-induced reactivation of rhesus monkey, swine and guinea pig erythrocyte acetylcholinesterase following inhibition by sarin or paraoxon, using a perfusion model for the real-time determination of membrane-bound acetylcholinesterase activity.

    Science.gov (United States)

    Herkert, Nadja M; Lallement, Guy; Clarençon, Didier; Thiermann, Horst; Worek, Franz

    2009-04-28

    Recently, a dynamically working in vitro model with real-time determination of membrane-bound human acetylcholinesterase (AChE) activity was shown to be a versatile model to investigate oxime-induced reactivation kinetics of organophosphate- (OP) inhibited enzyme. In this assay, AChE was immobilized on particle filters which were perfused with acetylthiocholine, Ellman's reagent and phosphate buffer. Subsequently, AChE activity was continuously analyzed in a flow-through detector. Now, it was an intriguing question whether this model could be used with erythrocyte AChE from other species in order to investigate kinetic interactions in the absence of annoying side reactions. Rhesus monkey, swine and guinea pig erythrocytes were a stable and highly reproducible enzyme source. Then, the model was applied to the reactivation of sarin- and paraoxon-inhibited AChE by obidoxime or HI 6 and it could be shown that the derived reactivation rate constants were in good agreement to previous results obtained from experiments with a static model. Hence, this dynamic model offers the possibility to investigate highly reproducible interactions between AChE, OP and oximes with human and animal AChE.

  1. Effects of sex and early maternal abuse on adrenocorticotropin hormone and cortisol responses to the corticotropin-releasing hormone challenge during the first 3 years of life in group-living rhesus monkeys.

    Science.gov (United States)

    Sanchez, Mar M; McCormack, Kai; Grand, Alison P; Fulks, Richelle; Graff, Anne; Maestripieri, Dario

    2010-01-01

    In this study we investigated the development of the hypothalamic-pituitary-adrenal (HPA) axis in 21 group-living rhesus monkeys infants that were physically abused by their mothers in the first few months of life and in 21 nonabused controls. Cortisol and adrenocorticotropin hormone (ACTH) responses to a corticotropin-releasing hormone (CRH) challenge were assessed at 6-month intervals during the subjects' first 3 years of life. Abused infants exhibited greater cortisol responses to CRH than controls across the 3 years. Abused infants also exhibited blunted ACTH secretion in response to CRH, especially at 6 months of age. Although there were no significant sex differences in abuse experienced early in life, females showed a greater cortisol response to CRH than males at all ages. There were no significant sex differences in the ACTH response to CRH, or significant interactions between sex and abuse in the ACTH or cortisol response. Our findings suggest that early parental maltreatment results in greater adrenocortical, and possibly also pituitary, responsiveness to challenges later in life. These long-term alterations in neuroendocrine function may be one the mechanisms through which infant abuse results in later psychopathologies. Our study also suggests that there are developmental sex differences in adrenal function that occur irrespective of early stressful experience. The results of this study can enhance our understanding of the long-term effects of child maltreatment as well as our knowledge of the development of the HPA axis in human and nonhuman primates.

  2. Behavioral effects in monkeys of racemates of two biologically active marijuana constituents.

    Science.gov (United States)

    Scheckel, C L; Boff, E; Dahlen, P; Smart, T

    1968-06-28

    Both dl-Delta(8)- and dl-Delta(9)-tetrahydrocannabinol produced marked alterations of behavior in rhesus and squirrel monkeys. Squirrel monkeys appeared to have visual hallucinations. Continuous avoidance behavior of squirrel monkeys was stimulated by both drugs, but high doses of dl-Delta(9)-tetrahydrocannabinol also caused depression after the stimulant phase. Complex behavior involving memory and visual discrimination in rhesus monkeys was markedly disrupted by both drugs.

  3. Metacognition in Monkeys during an Oculomotor Task

    Science.gov (United States)

    Middlebrooks, Paul G.; Sommer, Marc A.

    2011-01-01

    This study investigated whether rhesus monkeys show evidence of metacognition in a reduced, visual oculomotor task that is particularly suitable for use in fMRI and electrophysiology. The 2-stage task involved punctate visual stimulation and saccadic eye movement responses. In each trial, monkeys made a decision and then made a bet. To earn…

  4. Metacognition in Monkeys during an Oculomotor Task

    Science.gov (United States)

    Middlebrooks, Paul G.; Sommer, Marc A.

    2011-01-01

    This study investigated whether rhesus monkeys show evidence of metacognition in a reduced, visual oculomotor task that is particularly suitable for use in fMRI and electrophysiology. The 2-stage task involved punctate visual stimulation and saccadic eye movement responses. In each trial, monkeys made a decision and then made a bet. To earn…

  5. Prototype Abstraction by Monkeys ("Macaca Mulatta")

    Science.gov (United States)

    Smith, J. David; Redford, Joshua S.; Haas, Sarah M.

    2008-01-01

    The authors analyze the shape categorization of rhesus monkeys ("Macaca mulatta") and the role of prototype- and exemplar-based comparison processes in monkeys' category learning. Prototype and exemplar theories make contrasting predictions regarding performance on the Posner-Homa dot-distortion categorization task. Prototype theory--which…

  6. Spatial information processing in humans and monkeys

    NARCIS (Netherlands)

    Oleksiak, A.

    2010-01-01

    In this thesis a series of experiments are described on human volunteers and rhesus monkeys (Macaca mulatta) in the context of spatial information processing. In the first single-unit recording experiments in monkeys a spatial summation algorithm was investigated. The responses of single neurons to

  7. Dentofacial three-dimensional changes after maxilla retraction with zygomatic implant anchorage in rhesus monkeys%颧骨种植体支抗后牵引猴上颌骨颅颌面三维形态学研究

    Institute of Scientific and Technical Information of China (English)

    史聪翀; 张晓蓉; 黄家昕; 邓怡

    2011-01-01

    Objective: To observe dentofacial three-dimensional changes after maxillar retraction with zygomatic implant anchorage in rhesus monkeys. Methods: 4 young male rhesus monkeys were employed. Maxillar retraction was performed with zygomatic implant anchorage in 3 monkeys( 1 for 1.5 month and 2 for 3 month observation), 1 without treatment was used as the control. Spiral CT images were used to analysis the dentofacial three dimensional changes after the retraction. Results: There was obvious sagital backward movement in upper dentition, about 2.5 mm in 1.5 month test group and more obvious sagital backward movement in both upper dentition and maxilla in 3 month test group. The vertical and horizontal positions did not change obviously in both upper dentition and maxilla.ANS-PNS plane rotated clockwise slightly. 0.98° in 1. 5 month test group and 1.39° in 3 month test group respectively. Conclusion: Zygomatic miniplate implants can be utilized as the stable and effective anchorage not only to inhibit maxilla from growing forward but also to retract maxilla distally with slight rotation.%目的:运用螺旋CT三维重建评价颧骨种植体支抗向后牵引猴上颌骨对颅颌面三维方向的矫形作用.方法:选用生长发育期恒河猴4只,3只用于研究(1只牵引1.5月、2只牵引3月),1只作为对照;实验前后分别行CT扫描及三维重建,测量各标志点的变化,分析颅颌面三维方向的矫形作用.结果:与对照组相比,1.5月组主要表现为上牙弓矢状向的变化,后移约2.5 mm,垂直向、水平向均无明显变化;3月组上牙弓矢状向变化更为明显,后移约3.8 mm,上颌骨后移约2.5 mm.硬腭平面相对于前颅底平面发生轻度顺时针旋转,1.5月时为0.98°,3月时为1.39°.结论:颧骨微钛板种植体支抗能有效后牵引上颌骨及上牙弓、抑制上颌矢状向发育,垂直向及水平向改变不明显.

  8. 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.

  9. Dynamics of T-cell memory subtypes in SIV infected Chinese rhesus monkeys%中国恒河猴感染SIV后T淋巴细胞初始、记忆亚群的变化

    Institute of Scientific and Technical Information of China (English)

    陈颂; 鲍琳琳; 卢葳; 吴小闲; 卢耀增; 潘菊华; 王阶; 黄世敬; 赖春辉; 郭卫中; 孙丽华

    2012-01-01

    目的:对中国恒河猴感染猴免疫缺陷病毒(SIV)后CD4 T初始、记忆亚群的细胞进行分析,了解各亚群的变化规律以及在AIDS发病过程中的意义.方法:使用SIVmac239毒株感染20只中国恒河猴,观察18个月;在感染前、后各时间点,使用实时荧光定量PCR(TaqMan探针法)进行病毒载量的检测;使用CD3/CD4/CD28/CD95表面标记的组合,进行CD4及其初始/记忆亚群比例的流式分析,并结合血常规检测的结果计算CD4及其各亚群的绝对数.结果:得到了CD4各个亚群在SIV感染后的变化曲线;并发现SIV感染后CD4减少的主体是中央型记忆(CM)CD4+T细胞;而初始型CD4+T在半数动物逐渐缓慢减少,但个体间差异较大.此外,还发现快速进展型RM449猴在死亡前其初始型及CM CD4仍较高,但其初始型CD4细胞在流式图上存在着类似"转化阻滞"的现象.结论:本研究展示了CD4细胞的初始、记忆亚群在感染SIV后的变化规律;对其进行细分研究,有助于更准确地了解体内免疫状态的变化,为临床疗效观察、免疫状态评估等提供参考.%Objective:To explore the dynamics of T-cell naive/memory subsets in SIV infected Chinese rhesus monkeys. Methods: 20 Chinese rhesus monkeys were infected by SIVmac239, and their plasma viral load were determined by quantitative Taqman real-time RT-PCR analysis within a follow-up period of 18 months. Moreover, proportions of their CD4+ T cells and its naive/memory subsets were analyzed by flow cytometry using a combination of surface markers CD3/CD4/CD28/CD95, by which the absolute cell counts of CD4 and its subsets were also computed based on the routine blood tests. Results: Dynamics of the T-cell naive/memory subsets including their percentages and absolute counts were illustrated. Moreover, central memory CD4 showed to be the majority of cell-loss after SIV infection, which decreased more significantly and accordantly than total CD4, and should be further evaluated

  10. Insulin-like growth factor I (IGF-I) replacement during growth hormone receptor antagonism normalizes serum IGF-binding protein-3 and markers of bone formation in ovariectomized rhesus monkeys.

    Science.gov (United States)

    Wilson, M E

    2000-04-01

    Previous work from this laboratory has shown that the constant sc infusion of insulin-like growth factor I (IGF-I) to normal pituitary monkeys results in a sustained elevation in circulating concentrations of IGF-binding protein-3 (IGFBP-3), whereas the acute administration of IGF-I to monkeys pretreated with a GH receptor antagonist produces a brief, but significant, elevation in serum IGFBP-3. The present study tested the hypothesis that the constant infusion of IGF-I would normalize serum concentrations of IGFBP-3 in females treated with the GH receptor antagonist. To assess the biological significance of these effects, serum levels of the acid-labile subunit (ALS) and biomarkers for bone formation, osteocalcin, and collagen type I C-terminal propeptide, were also examined. Five female rhesus monkeys were studied over 21 consecutive days involving 7 days of baseline, 7 days of treatment with the GH receptor antagonist (1.0 mg/kg-week, sc), and 7 days of treatment with the GH receptor antagonist supplemented with IGF-I (120 microg/kg x day, sc infusion with osmotic minipump). Within 48 h of the initiation of treatment with the GH receptor antagonist, serum IGF-I and IGFBP-3 were decreased by 40% and 18% from baseline, respectively, and levels continued to decline through the remainder of treatment. However, within 48 h of the initiation of IGF-I administration during GH receptor antagonist treatment, both serum IGF-I and IGFBP-3 were elevated and normalized to baseline values. Serum concentrations of ALS were also decreased by GH antagonism, but levels increased in some (n = 2), but not all, subjects upon administration of IGF-I. Size exclusion ultrafiltration indicated that the amount of IGF-I found in the high molecular mass complex (>100 kDa) decreased significantly during GH antagonism, but was similar during the baseline and IGF-I infusion phases. Finally, treatment with the GH receptor antagonist also significantly reduced serum levels of osteocalcin and

  11. Effects of direct- and indirect-acting serotonin receptor agonists on the antinociceptive and discriminative stimulus effects of morphine in rhesus monkeys.

    Science.gov (United States)

    Li, Jun-Xu; Koek, Wouter; Rice, Kenner C; France, Charles P

    2011-04-01

    Serotonergic (5-HT) systems modulate pain, and drugs acting on 5-HT systems are used with opioids to treat pain. This study examined the effects of 5-HT receptor agonists on the antinociceptive and discriminative stimulus effects of morphine in monkeys. Morphine increased tail-withdrawal latency in a dose-related manner; 5-HT receptor agonists alone increased tail-withdrawal latency at 50 °C but not 55 °C water. The antinociceptive effects of morphine occurred with smaller doses when monkeys received an indirect-acting (fenfluramine) or direct acting (8-OH-DPAT, F13714, buspirone, quipazine, DOM, and 2C-T-7) agonist. The role of 5-HT receptor subtypes in these interactions was confirmed with selective 5-HT(1A) (WAY100635) and 5-HT(2A) (MDL100907) receptor antagonists. None of the 5-HT drugs had morphine-like discriminative stimulus effects; however, fenfluramine and 5-HT(2A) receptor agonists attenuated the discriminative stimulus effects of morphine and this attenuation was prevented by MDL100907. The 5-HT(1A) receptor agonists did not alter the discriminative stimulus effects of morphine. Thus, 5-HT receptor agonists increase the potency of morphine in an assay of antinociception, even under conditions where 5-HT agonists are themselves without effect (ie, 55 °C water), without increasing (and in some cases decreasing) the potency of morphine in a drug discrimination assay. Whereas 5-HT(2A) receptor agonists increase the potency of morphine for antinociception at doses that have no effect on the rate of operant responding, 5-HT(1A) receptor agonists increase the potency of morphine only at doses that eliminate operant responding. These data suggest that drugs acting selectively on 5-HT receptor subtypes could help to improve the use of opioids for treating pain.

  12. Growth and developmental parameters and behavioral characteristics of infant rhesus monkeys%恒河猴幼猴出生后生长发育参数背景数据及其行为学特征

    Institute of Scientific and Technical Information of China (English)

    梁志刚; 曾文; 吴明玲; 曾利才; 姚尊伟; 易思瑞; 李蓉; 曹东; 毕凤均; 龚立

    2016-01-01

    记忆优于雄性幼猴。本研究建立了恒河猴幼猴出生后12个月生长发育参数的背景数据及神经行为学特征,为恒河猴生殖发育毒性评价提供了参考依据及数据支持。%Objective To explore the growth and developmental parameters and behavioral characteristics of rhesus monkeys during the first year of birth and to establish the background data.Methods A total of 18 (♂=11,♀=7 ) infant rhesus monkeys born from individually caged mothers and with known genetic background and postnatal days were monitored monthly for body weight, body height, head circumference, chest circumference, forelimb length, hind limb length, crown-rump length, tail length and anal-genital distance from postnatal day ( PND) 1 to 360, while hematology, blood chemistry and lymphocyte subsets were examined on PND 28, 175 and 360, and finger maze test was carried out on PND 208.Results The body weight showed linear growth with no significant difference between genders (P>0.05). Except for the anal-genital distance of male infants was significantly greater than that of female infants ( P0.05).Compared with that at PND28, TP and BUN were significantly increased (P0.05) at PND 175 and 360.Compared with that at PND28, CD4 +and CD4 +/CD8 +were significantly decreased ( P<0.01) while CD8+significantly increased ( P<0.01) at PND175 and 360.The number of sessions to solve task 2 in learning test was significantly greater than other tasks with females significantly less than males ( P<0.05) .The females had higher correct rate than males in the 2-day random memory test (P<0.05).Conclusions Body weight and morphological parameters show a linear growth.The PND.The RBC, HGB, LYMPH, TP, BUN, ALP, CD4 +, CD8 +and CD4 +/CD8+in hematology, blood chemistry and lymphocyte subsets show relevant changes to the growth and development of organs and systems in infants, which should be highly concerned in drug evaluation.The finger maze test indicates that female infants

  13. 恒河猴五日热巴尔通体的分离和柠檬酸合成酶基因的序列分析%Isolation of Bartonella quintana from rhesus monkeys and analysis of the gltA gene sequence

    Institute of Scientific and Technical Information of China (English)

    隋丽华; 曾林; 张广州; 白杰英; 赵彦斌; 张小飞; 陈旖; 赵爽; 孙兆增

    2012-01-01

    目的 初步研究巴尔通体在恒河猴体内的存在情况,并分析其柠檬酸合成酶(gltA)的基因序列,判断巴尔通体的种属.方法 16只来自福建的恒河猴,用血琼脂培养基分离可能存在的巴尔通体.根据NCBI数据库上的巴尔通体gltA的基因序列,设计一对引物,以巴尔通体菌落为模板进行扩增,将获得的序列进行克隆测序.结果 从3只恒河猴体内成功分离到了巴尔通体病原,并获得了巴尔通体gltA全长基因序列,测序结果表明该序列与五日热巴尔通体同源性99%.结论 福建来源的恒河猴种群携带巴尔通体病原,巴尔通体流行地区可能存在鼠与灵长类动物之间病原体的流行和传播.%Objective To investigate the presence of Bartonella in rhesus monkeys and to analyze the gltA gene sequence. Methods Bartonella were isolated from 16 rhesus monkeys coming from Fujian province, isolated with Guy's culture-medium. According to the reported complete nucleotide sequence of gltA gene in NCBI, one pairs of primers were designed and synthesized. The gltA gene was amplified from the lysate of Bartonella colony by PCR. Then the bands were cloned and sequenced. Results Bartonella pathogen was successfully isolated from 3 rhesus monkeys. The sequencing of gltA showed that the isolated Bartonella belonged to Bartonella quintana, with a homology of 98% . Conclusion Bartonella pathogen is existed in rhesus mokey coming from Fujian province. The prevalence and spreading of Bartonella infection may happen between mouse and primate in the epidemic area.

  14. 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.

  15. Influence of Leydig Cells on Estradiol Secretion of Sertoli Cells in Rhesus Monkey%恒河猴睾丸间质细胞对支持细胞分泌雌二醇的影响

    Institute of Scientific and Technical Information of China (English)

    王训立; 谢金东; 周建华

    2012-01-01

    采用无血清培养的方法,分析了促肾上腺激素皮质激素(adrenocorticotropic hormone,ACTH)、黄体生成素( luteinizing hormone,LH)、cAMP、内啡肽(endorphin)和纳络酮(naloxone)对原代共培养的恒河猴(Macaca mulatta)睾丸间质细胞与支持细胞雌二醇分泌水平的影响.结果显示:ACTH、LH、cAMP和纳络酮对原代共培养恒河猴睾丸间质细胞与支持细胞的雌二醇分泌水平具有促进作用,并且这种影响与共培养的间质细胞数量呈线性关系,即共培养的间质细胞数量增加,雌二醇分泌水平亦明显上升;而内啡肽对原代共培养恒河猴睾丸间质细胞与支持细胞的雌二醇分泌水平有明显的抑制作用.研究表明,恒河猴睾丸的间质细胞对支持细胞分泌雌二醇具有调节作用.%By using serum-free co-culture of Leydig cells and Sertoli cells isolated from Rhesus Monkey(Macaca mulatta) , we analyzed the effect of adrenocorticotropic hormone ( ACTH) , luteinizing hormone ( LH) , cAMP, endorphin, and naloxone on the secretion of estradiol. We showed that ACTH, LH, cAMP, and naloxone stimulated estradiol production in co-cultured system and this stimulation was enhanced by increased Leydig cells. We also showed that endorphin inhibited estradiol secretion by Leydig cells and Sertoli cells when a certain amount of Leydig cells were present. Thus, these results suggest the amount of Leydig cells may play an important role in estradiol production in Leydig-Sertoli cells co-culture.

  16. PCR test of Helicobacter pylori and“Helicobacter macacae”infections in rhesus and cynomolgus monkey breading colonies%PCR 检测实验恒河猴和食蟹猴群体中幽门螺杆菌和“猕猴螺杆菌”的感染

    Institute of Scientific and Technical Information of China (English)

    王立鹏; 李永旺; 郭连香; 时长军

    2016-01-01

    Objective To investigate the status of Helicobacter pylori and “Helicobacter macacae” infection in rhesus and cynomolgus monkeys in China.Methods With the use of 16S rRNA specific primers for Helicobacter spp and Helicobacter pylori ( HP ) from published literatures, and new 16S rRNA specific primers designed for “Helicobacter macacae” ( HM ) , we investigated the infection status of these two Helicobacter spps in both of 45 rhesus and 90 cynomolgus monkeys by qPCR or conventional PCR on stool samples.Results All three primer sets for 16S rRNA exhibited excellently sensitivity and specificity.Both the infection rates of HP and HM were 100% among 45 young adult rhesus monkeys.The infection rate of HP and HM in 90 young adult cynomolgus monkeys were 100% and 97.8%, respectively.Conclusions Helicobacter pylori and “Helicobacter macacae” are present in almost every artificially bred adult rhesus and cynomolgus individuals which may adversely affect the health of laboratory monkeys and the accuracy of related animal experiments.%目的:调查国内实验恒河猴和食蟹猴中幽门螺杆菌和“猕猴螺杆菌”的感染情况。方法参考文献中的螺杆菌属16S rRNA和幽门螺杆菌16S rRNA的引物序列,和新设计的“猕猴螺杆菌”16S rRNA特异性引物,在人工养殖的45只成年恒河猴和90只成年食蟹猴粪便样本中,通过qPCR或常规PCR检测来初步调查这两种猕猴中两种螺杆菌的感染情况。结果在恒河猴中幽门螺杆菌和“猕猴螺杆菌”的感染率均为100%,在食蟹猴中幽门螺杆菌和“猕猴螺杆菌”的感染率分别为100%和97.8%。结论证实我国人工繁育饲养的恒河猴和食蟹猴普遍存在“猕猴螺杆菌”感染。幽门螺杆菌和“猕猴螺杆菌”几乎同时存在于所有人工繁育的实验猴个体中,可能会对这两种猕猴的健康以及相关动物实验结果的准确性存在不利影响。

  17. 模拟失重对恒河猴腰椎运动单元生物力学的影响%Effects of simulated weightlessness on biomechanics of motion unit of rhesus monkey lumbar vertebra

    Institute of Scientific and Technical Information of China (English)

    王晓平; 吴志宏; 陆明; 马培; 陈志明; 袁伟; 赵福江; 赵浩; 任冬云; 马华松

    2016-01-01

    BACKGROUND:It is generaly believed that the spine wil be extended, and vertebral muscle atrophy, bone loss of vertebral body, increased height and area of intervertebral disc, changes of composition of intervertebral disc wil occur in the condition of weightlessness. These are likely to be the cause of high incidence of low back pain. OBJECTIVE:To observe changes in lumbar spine bone microstructure analysis of simulated weightlessness on rhesus lumbar spine biomechanics. METHODS:Fourteen young rhesus monkeys were randomly divided into two groups: control group (n=7;free activities in the cage during the experiment), and experimental group (n=7; the use of head-down-10° on a special bed by bundle lying to simulate weightlessness). RESULTS AND CONCLUSION:(1) The results of Micro-CT examination: in the experimental group, structure model index in trabecular bone of increased. Trabecular bone changed from plate-like to the rod-like change. The intersection number of bone tissue in unit length to non-bone tissue declined. The average width of the canal between the trabecular bone increased, suggesting that there have been signs of osteoporosis in the experimental group. (2) Under an optical microscope, in the experimental group, bone hyperplasia line was disordered and irregular. Thick endplate trabecularbone became smal, shalow, and arranged substantialy perpendicular to the direction of trabecular bone and cartilage endplate. The closer the endplate surface, the smaler trabecular bone was. Compared with the control group, these smal trabecular bones were thin and curved. Bone marrow cavity was oval. The degree of the connection between the trabecular bones is poor, reflecting the structural characteristics of significant osteoporosis. (3) It is indicated that weightlessness affected the biomechanical properties of rhesus lumbar motion unit.%背景:一般认为在失重状态下,脊柱会出现异常延长、椎旁肌萎缩、椎体骨量丢失、椎间盘的高

  18. 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...

  19. 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...

  20. Induction of Protective Immune Response in Mice and Rhesus Monkeys by Immunization with Fusion Protein of Cholera Toxin B Subunit and Multiples of Plasmodium falciparum%重组霍乱毒素B亚基与疟原虫多表位融合蛋白 的免疫保护作用研究

    Institute of Scientific and Technical Information of China (English)

    曹诚; 李平; 石成华; 钟辉; 时运林; 李杰之; 马清钧

    2000-01-01

    Recombinant fusion protein of cholera toxin B subunit (CTB) and poly-valent protective epitopes of plasmodium falciparum was given to i. m to C57BL/6j mice and rhesus monkeys three times. In rhesus monkeys, high level of antibodies for CTB (1:6400) and malaria epitopes (1:3200) amtobpdoes were elicited as well as the specific CTL activity for P. plasmodium. After the mice were challenged with sporozoites of P. yeolli, about 50 % of them were protected from the patent infection. A blood-stage challenge with 108 of P. cynomolgi parasite were given to rhesus monkeys, which showed that two animals in control group were patent infection for at least 30 days, in contrast, the two animals immunized were recovered respectively at the day of 11 and 15 after challenges. The results suggested that cholera toxin acts as an effective adjuvent in the development of malaria vaccine.%对以霍乱毒素B亚基为载体蛋白的重组疟疾多价抗原在小鼠及恒河猴中的免疫原性及对相应疟原虫感染的免疫保护作用进行了研究。结果表明:该抗原免疫小鼠后,对约氏疟子孢子攻击的保护率在50%左右;恒河猴免疫后用1×108食蟹疟裂殖子攻击,对照组2只动物在攻击后4d感染,感染持续30d以上;免疫组2只动物中,两只动物在感染6~7d后完全恢复,且1只推迟3d感染,说明该抗原具有免疫保护作用。

  1. 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.

  2. 弹簧圈置入法建立恒河猴可逆性大脑中动脉阻塞模型的初步研究%Establishment of a reversible middle cerebral artery occlusion model with endovascular coil placement in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    赵博; 李胜利; 卢静; 凌锋; 吉训明; 尚国伟; 陈健; 耿晓坤; 叶新; 徐国勋; 王钜; 郑加生; 李宏军

    2013-01-01

    Objective To establish a reversible middle cerebral artery (MCA) occlusion model with endovascular coil placement in rhesus monkeys. Methods Four adult male healthy rhesus monkeys were selected as experimental animals. A coil (2 mm × 10 cm) was implanted into the origin of MCA (undetach-able) using the endovascular interventional techniques. The MCA blood flow was blocked completely for 2 hours,and then the coil was withdrawn and the MCA blood flow was restored. A reversible MCA occlusion model was induced initially. Whether the animal model successful or not was evaluated by digital subtraction angiography (DSA) , magnetic resonance angiography (MRA) , magnetic resonance imaging (MRI) , and neurological deficits. Results The coils were implanted into the origins of MCA successfully in 4 rhesus monkeys. After coil release,the MCA blood flow was blocked completely. The distal blood vessels did not develop. Being blocked for 2 hours,the MCA blood flow was restored after withdrawing the coils. Being blocked for 2 hours,MRI examination showed that T1- and T2-weighted images of the 4 animals did not reveal any infarction lesions. The cortex and basal ganglia on the diffusion-weighted images (DWI) appeared abnormal high signals,and the brain hemisphere of MCA blocked side was swollen. MRA examina- tion showed that the MCA was blocked completely. The animals had the symptoms of neurological deficit, such as hemiplegia and mouth askew. Conclusion Inducing a reversible MCA occlusion model with en-dovascular coil technique in rhesus monkeys has a high successful rate and mild injury.%目的 采用血管内弹簧圈置入法初步建立恒河猴可逆性大脑中动脉阻塞模型.方法 选择4只成年健康恒河猴为实验动物,采用血管内介入技术,将1枚弹簧圈(2 mm×10 cm)置入大脑中动脉(MCA) 起始部(不解脱弹簧圈),完全阻断MCA血流2 h,回收弹簧圈,恢复MCA血流灌注,初步建立恒河猴可逆性大脑中动脉阻塞模型.通过DSA

  3. E型沙眼衣原体重组主外膜蛋白疫苗对恒河猴的免疫效应%Immune responses induced by the recombinant major outer membrane protein vaccine against Chlamydia trachomatis E serotype in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    李宜儒; 齐蔓莉; 刘全忠; 姚卫锋; 盛彩虹; 冯斌; 展小飞; 李玲杰; 尤聪; 李艳飞; 刘原君

    2012-01-01

    [目的]探讨E型重组主外膜蛋白(rMOMP)对恒河猴诱导产生的特异性免疫应答效应.[方法]恒河猴分3组,每组2只,分别为佐剂蛋白组、佐剂组、对照组.各组均于第0(免疫起始周)、2、4周双侧肱三头肌注射蛋白疫苗、佐剂和磷酸盐缓冲液(PBS).末次免疫后2周,酶联免疫吸附试验(ELISA)检测恒河猴血清中沙眼衣原体特异性IgG抗体和干扰素γ(IFN-γ),以及阴道冲洗液中沙眼衣原体特异性sIgA抗体,MTT法检测恒河猴淋巴细胞特异性增殖反应,观察恒河猴的迟发型超敏反应,以及恒河猴血清抗体中和试验,同源攻击后免疫荧光检测衣原体.用SPSS 14.0软件进行单向方差分析和LSD法进行组间多重比较.[结果]佐剂蛋白组恒河猴血清衣原体特异性IgG抗体A405值为1.718±0.213,淋巴细胞增殖指数为7.012±1.026,IFN-γ水平为(1086.000±121.730) ng/L,迟发型超敏反应皮丘直径为(11.000±2.134) mm;佐剂组分别为0.841±0.315、4.473±1.850、(409.000±53.440)ng/L、(3.000±0.914) mm;对照组分别为0.791±0.437、1.426±1.104、(162.000±48.046) ng/L、0.佐剂蛋白组各项指标与佐剂组和对照组比较,差异均有统计学意义.提示蛋白疫苗能诱导对沙眼衣原体血清E型株的特异性免疫应答.同源攻击后佐剂蛋白组衣原体持续阳性5周后转阴性,佐剂组及对照组持续阳性.[结论]沙眼衣原体rMOMP能刺激恒河猴产生特异性的体液和细胞免疫应答,能诱导恒河猴产生抗沙眼衣原体保护效应.%[Objective] To observe the specific immune responses induced by the recombinant major outer membrane protein (rMOMP) vaccine against Chlamydia trachomatis E serotype in rhesus monkeys.[Methods] Six rhesus monkeys were equally divided into three groups:adjuvant and protein group vaccinated with purified rMOMP and Freund's adjuvants,adjuvant group immunized with Freund's adjuvants only,and control group immunized with phosphate buffer.All the

  4. SPECT Imaging Study of the Biodistribution of Beta - CIT in the Whole- Body of Healthy Rhesus Monkeys%β-CIT在/正常恒河猴体内分布的SPECT显像研究

    Institute of Scientific and Technical Information of China (English)

    翁中芳; 孙文善; 刘振国; 李培勇; 沈鸣华; 匡琴芳; 朱承谟; 陈生弟

    2000-01-01

    目的 研究多巴胺转运蛋白(DAT)放射性配体123I-、131I-β-CIT在正常恒河猴体内的分布,探讨其临床应用前景。方法 于正常恒河猴肘静脉处弹丸注射123Iβ-CIT(9mCi)或131I-β-CIT(