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Cynomolgus Macaques (cynomolgu + macaque)
Selected AbstractsExperimental respiratory anthrax infection in the common marmoset (Callithrix jacchus)INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2008Mark S. Lever Summary Inhalational anthrax is a rare but potentially fatal infection in man. The common marmoset (Callithrix jacchus) was evaluated as a small non-human primate (NHP) model of inhalational anthrax infection, as an alternative to larger NHP species. The marmoset was found to be susceptible to inhalational exposure to Bacillus anthracis Ames strain. The pathophysiology of infection following inhalational exposure was similar to that previously reported in the rhesus and cynomolgus macaque and humans. The calculated LD50 for B. anthracis Ames strain in the marmoset was 1.47 × 103 colony-forming units, compared with a published LD50 of 5.5 × 104 spores in the rhesus macaque and 4.13 × 103 spores in the cynomolgus macaque. This suggests that the common marmoset is an appropriate alternative NHP and will be used for the evaluation of medical countermeasures against respiratory anthrax infection. [source] Prevalence of antibody reaction with cercopithecine herpesvirus 1 antigen in Macaca cyclopis, Macaca fascicularis, and Papio anubis in TaiwanJOURNAL OF MEDICAL PRIMATOLOGY, Issue 6 2007F. Lee Abstract Background and Methods, A total of 284 non-human primate sera were collected between December 2004 and September 2005 and tested by a commercially available dot immunobinding assay for the antibodies to cercopithecine herpesvirus 1, an alphaherpesvirus with high mortality for infected humans. Results, Seropositive rates were 58% among non-human primates from animal shelters and 38% among those from zoos and academic institutes. Positive reactors were found in three species, the Formosan macaque (Macaca cyclopis; 57%), the cynomolgus macaque (Macaca fascicularis; 11%) and the olive baboon (Papio anubis; 68%). Conclusions, Our results showed that natural infection by cercopithecine herpesvirus 1 in Formosan macaques was highly prevalent, and to a certain extent reflected the situation of the wild populations in Taiwan. The findings raised the issues of zoonotic public health and the occupational health of primate workers. High positive rate in olive baboons was also found, although, it cannot be ruled out that the positivity was due to cross-reactivity between cercopithecine herpesvirus 1 and other herpesviruses. [source] MHC haplotype frequencies in a UK breeding colony of Mauritian cynomolgus macaques mirror those found in a distinct population from the same geographic originJOURNAL OF MEDICAL PRIMATOLOGY, Issue 1 2009Edward T. Mee Abstract Background, Mauritian cynomolgus macaques have greatly restricted genetic diversity in the MHC region compared to other non-human primates; however, the frequency of common MHC haplotypes among captive-bred populations has not been reported. Methods, Microsatellite PCR was used to determine MHC haplotype frequencies among captive macaques at a UK breeding facility. Allele-specific PCR and reference strand conformational analysis were used to determine the allele expression profile of a subset of animals. Results, Haplotypes H3 (21%) and H1 (19%) were most common in the captive population of Mauritian cynomolgus macaques. Predicted alleles were detected by allele-specific PCR-SSP in 98% of animals. Allele expression profiles were similar in animals with identical haplotypes. Conclusions, Mauritian cynomolgus macaques in the UK breeding facility have restricted MHC diversity comparable to a previously described population. Microsatellite-derived haplotypes are highly predictive of allele expression. A selective breeding program has been established to produce MHC-identical animals for biomedical research. [source] SHIV89.6P pathogenicity in cynomolgus monkeys and control of viral replication and disease onset by human immunodeficiency virus type 1 Tat vaccineJOURNAL OF MEDICAL PRIMATOLOGY, Issue 3-4 2000Aurelio Cafaro The Tat protein of human immunodeficiency virus (HIV) is produced very early after infection, plays a key role in the virus life cycle and in acquired immunodeficiency syndrome (AIDS) pathogenesis, is immunogenic and well conserved among all virus clades. Notably, a Tat-specific immune response correlates with non-progression to AIDS. Here, we show that a vaccine based on the Tat protein of HIV blocks primary infection with the simian/human immunodeficiency virus (SHIV)89.6P and prevents the CD4 T cell decline and disease onset in cynomolgus monkeys. No signs of virus replication were found in five out of seven vaccinated macaques for almost 1 year of follow-up. Since the inoculated virus (derived from rhesus or from cynomolgus macaques) is shown to be highly pathogenic in cynomolgus macaques, the results indicate efficacy of Tat vaccination in protection against highly pathogenic virus challenge. Finally, the studies of the Tat-specific immunological responses indicate a correlation of protection with a cytotoxic T cell response. Thus, a Tat-based vaccine is a promising candidate for preventive and therapeutic vaccination in humans. [source] Validation of multi-detector computed tomography as a non-invasive method for measuring ovarian volume in macaques (Macaca fascicularis)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 6 2010Jeryl C. Jones Abstract The purpose of this study was to validate low radiation dose, contrast-enhanced, multi-detector computed tomography (MDCT) as a non-invasive method for measuring ovarian volume in macaques. Computed tomography scans of four known-volume phantoms and nine mature female cynomolgus macaques were acquired using a previously described, low radiation dose scanning protocol, intravenous contrast enhancement, and a 32-slice MDCT scanner. Immediately following MDCT, ovaries were surgically removed and the ovarian weights were measured. The ovarian volumes were determined using water displacement. A veterinary radiologist who was unaware of actual volumes measured ovarian CT volumes three times, using a laptop computer, pen display tablet, hand-traced regions of interest, and free image analysis software. A statistician selected and performed all tests comparing the actual and CT data. Ovaries were successfully located in all MDCT scans. The iliac arteries and veins, uterus, fallopian tubes, cervix, ureters, urinary bladder, rectum, and colon were also consistently visualized. Large antral follicles were detected in six ovaries. Phantom mean CT volume was 0.702±SD 0.504,cc and the mean actual volume was 0.743±SD 0.526,cc. Ovary mean CT volume was 0.258±SD 0.159,cc and mean water displacement volume was 0.257±SD 0.145,cc. For phantoms, the mean coefficient of variation for CT volumes was 2.5%. For ovaries, the least squares mean coefficient of variation for CT volumes was 5.4%. The ovarian CT volume was significantly associated with actual ovarian volume (ICC coefficient 0.79, regression coefficient 0.5, P=0.0006) and the actual ovarian weight (ICC coefficient 0.62, regression coefficient 0.6, P=0.015). There was no association between the CT volume accuracy and mean ovarian CT density (degree of intravenous contrast enhancement), and there was no proportional or fixed bias in the CT volume measurements. Findings from this study indicate that MDCT is a valid non-invasive technique for measuring the ovarian volume in macaques. Am. J. Primatol. 72:530,538, 2010. © 2010 Wiley-Liss, Inc. [source] Estrogen/isoflavone interactions in cynomolgus macaques (Macaca fascicularis)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009J. Mark Cline Abstract Soy isoflavones are phytoestrogenic components of dietary soy, which are widely consumed for their potential health benefits. Soy isoflavones appear to decrease breast and endometrial cancer risk in human observational studies, but paradoxically stimulate growth of breast cancer cells in culture and uterine enlargement in rodents. We have shown that these compounds are not estrogenic in cynomolgus monkeys even at relatively high doses, but that they reduce estrogen-induced proliferative responses of the breast and endometrium. This effect may be mediated through estrogen receptor interactions and/or modulation of endogenous estrogen metabolism. Interindividual variation in isoflavone absorption and metabolism contributes to the degree of estrogen antagonistic effect. Our recent studies have also shown that individual isoflavone metabolites such as glyceollins may have unique selective estrogen receptor modulator-like activity, acting as tissue-specific antagonists without agonist activity. Rodent studies and human epidemiologic data suggest that timing of exposure and dose relative to endogenous estrogen concentrations are important determinants of effect, and studies of dietary soy on breast development and pubertal maturation are under way. Because soy isoflavones are both abundant in standard monkey chow diets and widely available as dietary supplements for human beings, these findings have broad relevance to the health of human and nonhuman primates. Am. J. Primatol. 71:722,731, 2009. © 2009 Wiley-Liss, Inc. [source] Social stress, visceral obesity, and coronary artery atherosclerosis: product of a primate adaptationAMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009Carol A. Shively Abstract Abdominal obesity is prevalent and often accompanied by an array of metabolic perturbations including elevated blood pressure, dyslipidemia, impaired glucose tolerance or insulin resistance, a prothrombotic state, and a proinflammatory state, together referred to as the metabolic syndrome. The metabolic syndrome greatly increases coronary heart disease (CHD) risk. Social stress also increases CHD although the mechanisms through which this occurs are not completely understood. Chronic stress may result in sustained glucocorticoid production, which is thought to promote visceral obesity. Thus, one hypothesis is that social stress may cause visceral fat deposition and the metabolic syndrome, which, in turn increases CHD. CHD is caused by coronary artery atherosclerosis (CAA) and its sequelae. Cynomolgus monkeys (Macaca fascicularis) are a well-established models of CAA. Social subordination may be stressful to cynomolgus monkeys and result in hypercortisolemia and exacerbated CAA in females. Herein is reviewed a body of literature which suggests that social stress increases visceral fat deposition in cynomolgus monkeys, that subordinate females are more likely than dominants to have visceral obesity, that females with visceral obesity have behavioral and physiological characteristics consistent with a stressed state, and that females with high ratios of visceral to subcutaneous abdominal fat develop more CAA. While these relationships have been most extensively studied in cynomolgus macaques, obesity-related metabolic disturbances are also observed in other primate species. Taken together, these observations support the view that the current obesity epidemic is the result of a primate adaptation involving the coevolution with encephalization of elaborate physiological systems to protect against starvation and defend stored body fat in order to feed a large and metabolically demanding brain. Social stress may be engaging these same physiological systems, increasing the visceral deposition of fat and its sequelae, which increase CHD risk. Am. J. Primatol. 71:742,751, 2009. © 2009 Wiley-Liss, Inc. [source] Primate models in women's health: inflammation and atherogenesis in female cynomolgus macaques (Macaca fascicularis)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009Thomas C. Register Abstract Female cynomolgus monkeys are excellent models for understanding cardiovascular disease and the relationships between inflammatory processes and conditions such as atherogenesis. This review summarizes published research findings obtained through comprehensive, multidisciplinary, multi-investigator studies in nonhuman primates over the past two decades. These studies examined the effects of exogenous estrogens and dietary soy protein/isoflavones (IFs) on atherosclerosis, circulating biomarkers, and tissue inflammation in pre- and postmenopausal female cynomolgus monkeys. Inflammation may play a role in the initiation and progression of disease, be a consequence of the disease, or both. Circulating and tissue biomarkers with inflammatory and anti-inflammatory characteristics (including adhesion molecules such as e-selectin, VCAM-1, and ICAM-1, chemokines such as MCP-1, cytokines such as interleukins, and acute phase reactants such as CRP, and others) may be useful indicators of disease status. Treatment of postmenopausal subjects with estrogen resulted in significant reductions in several key inflammatory mediators as well as atherosclerosis, while dietary IF had a more limited effect on inflammation and atherogenesis. Circulating concentrations of key inflammatory proteins, including monocyte-chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6), were associated with atherosclerosis and lesion characteristics in these animals. In premenopausal female monkeys, a diet enriched in soy protein reduced arterial inflammation as well as atherogenesis in comparison to a diet enriched in casein-lactalbumin. Expression levels of arterial inflammation associated genes (MCP-1, ICAM-1) and markers for inflammatory cell types (macrophages and T cells) correlated with plaque size, were differentially influenced by treatments, and represent potential targets for interventions. Arterial expression of estrogen receptor ,, the key mediator of estrogenic effects, was inversely correlated with plaque size and indices of inflammation, suggestive of an atheroprotective role. The findings provide additional evidence that circulating inflammatory markers (particularly MCP-1) may be useful indicators of atherosclerotic disease progression and responses to treatment in female primates, and that estrogens and dietary soy may inhibit atherogenesis in part through anti-inflammatory mechanisms. Am. J. Primatol. 71:766,775, 2009. © 2009 Wiley-Liss, Inc. [source] Influence of estradiol on cortisol secretion in ovariectomized cynomolgus macaques (Macaca fascicularis)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 1 2003R.C. Stavisky Abstract In an investigation of cortisol secretion in fully mature, ovariectomized cynomolgus monkeys (Macaca fascicularis), we compared monkeys that were given either placebo (OVX, n = 26) or 17, estradiol (E2 ) (EST, n = 26) in a daily oral dose. Serum cortisol concentrations were measured prior to the experimental manipulation and 3, 6, 9, and 12 months following initiation of treatment. Pretreatment cortisol values did not differ between groups. Assessment of the treatment period values revealed that cortisol concentrations were significantly higher (,10%) in the EST than in the OVX monkeys. Cortisol also varied significantly across periods of sampling. This time-dependent variation was attributable to elevations in months 6 and 9 (when daylight was generally long), relative to months 3 and 12 (when daylight was relatively short). The modest stimulatory effect of estrogen on corticosteroid production observed in this study is consistent with what has been seen in women, and contrasts with the more robust effects observed in New World monkeys. The possible relationship between season and cortisol secretion observed here has not been previously described in monkeys. Am. J. Primatol. 60:17,22, 2003. © 2003 Wiley-Liss, Inc. [source] Tumor necrosis factor neutralization results in disseminated disease in acute and latent Mycobacterium tuberculosis infection with normal granuloma structure in a cynomolgus macaque modelARTHRITIS & RHEUMATISM, Issue 2 2010Philana Ling Lin Objective An increased risk of tuberculosis has been documented in humans treated with tumor necrosis factor , (TNF,),neutralizing agents. In murine models, impaired signaling by TNF causes exacerbation of both acute and chronic infection associated with aberrant granuloma formation and maintenance. This study was undertaken to investigate immune modulation in the setting of TNF neutralization in primary and latent tuberculosis in a non-human primate model. Methods Cynomolgus macaques 4 years of age or older were infected with Mycobacterium tuberculosis and subjected to clinical, microbiologic, immunologic, and radiographic examinations. Monkeys were classified as having active or latent disease 6,8 months after infection, based on clinical criteria. Monkeys used in acute infection studies were randomized to receive either adalimumab (prior to and during infection) or no treatment. Monkeys with latent infection that were randomized to receive TNF-neutralizing agent were given either an inhibitor of soluble TNF, recombinant methionyl human soluble TNF receptor I (p55-TNFRI), or adalimumab. Control monkeys with latent infection were given no treatment or saline. Data from previously studied monkeys with active or latent disease were also used for comparison. Results Administration of TNF-neutralizing agents prior to M tuberculosis infection resulted in fulminant and disseminated disease by 8 weeks after infection. Neutralization of TNF in latently infected cynomolgus macaques caused reactivation in a majority of animals as determined by gross pathologic examination and bacterial burden. A spectrum of dissemination was noted, including extrapulmonary disease. Surprisingly, monkeys that developed primary and reactivation tuberculosis after TNF neutralization had similar granuloma structure and composition to that of control monkeys with active disease. TNF neutralization was associated with increased levels of interleukin-12, decreased levels of CCL4, increased chemokine receptor expression, and reduced mycobacteria-induced interferon-, production in blood but not in the affected mediastinal lymph nodes. Finally, the first signs of reactivation often occurred in thoracic lymph nodes. Conclusion These findings have important clinical implications for determining the mechanism of TNF neutralization,related tuberculosis. [source] | ||||||||||