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PubMed1986

Isolation of low-copy-number sequences that neighbor satellite DNA in mammals.

To investigate the role of satellite DNA in eukaryotic genomes, we isolated from an African green monkey (Cercopithecus aethiops) genomic library cloned segments containing the previously described deca-satellite linked to low-copy-number genomic sequences. Three such clones were obtained. The low-copy-number sequences in the three clones do not cross-hybridize suggesting that they derive from different genomic loci. The structure of one of the clones, lambda MkA, is described in detail. Subcloned segments containing the low-copy-number sequences from lambda MkA anneal to monkey, human and mouse genomic DNA. The subcloned probes were used to select clones containing homologous sequences from a second, independent monkey library as well as from human and mouse genomic libraries. Several of the newly isolated monkey clones hybridized to probes containing the species-specific deca- and alpha-satellites, confirming the genomic association of the low-copy-number sequence in lambda MkA with satellite DNA. Moreover, several of the human and mouse clones hybridized to species-specific human and mouse satellite DNAs, respectively. These experiments indicate that the low-copy-number sequence in lambda MkA and its association with satellite DNA is conserved in primates and rodents.

Animals↗
PubMed1990

Isolation of Mycoplasma moatsii from the intestine of wild Norway rats (Rattus norvegicus).

The intestinal tracts of twenty inbred SPF rats (LEW, BN, WKY, DA) and six wild Norway rats (Rattus norvegicus Berkenhout 1769) were investigated for mycoplasmas. Cultivation was in three different media. Mycoplasmas were not isolated from the intestine of the inbred SPF rats but were found in the epithelia and contents of caecum, colon and jejunum as well as in fecal samples of all of the wild Norway rats investigated. The mycoplasmas isolated all belonged to the same species, and were identified as Mycoplasma moatsii, originally isolated from grivit monkeys (Cercopithecus aethiops) and thought to be specific for this host.

Animals↗
PubMedDate not supplied

Hepatitis-E-virus-associated antigen: improved detection in stools by protein Fv removal.

ELISA detection of a hepatitis-E-virus-associated antigen (HEV-AAg) in stools was reappraised for its possible interference with a new Fab-binding factor, termed protein Fv, released during infectious hepatitis. Transaminase elevation, HEV-AAg discharge and Fv leakage appeared simultaneously in a Cercopithecus monkey inoculated with infected stools. Labelled normal, or immune human IgG, were compared with pre- and post-inoculation simian IgG, for HEV-AAg and Fv detection. Coated normal and patient human IgM were also compared to pre- and post-inoculation simian IgM in HEV-AAg and Fv capture assays. Simian IgM and beta-galactosidase-labelled simian IgG minimized Fv interference and appeared to be the best adapted system for HEV-AAg detection. Nevertheless, Fv was still the cause of false-positive interpretations in some cases; therefore adsorption with monoclonal IgM was required to ensure HEV specificity. The improved test was performed on stools from 30 Senegalese patients hospitalized for various sporadic attacks of viral hepatitis. HEV-AAg was detected in 6 out of 30 cases and no positivity was observed in patients suffering from hepatitis due to HAV, HBV, cytomegalovirus or Epstein-Barr virus. The specificity of the assay was confirmed by inhibition experiments with the sera from HEV-infected patients. Hence, this inhibition assay can also be used to detect serum antibodies to HEV-AAg.

Animals↗
PubMed2006

Development and biological properties of a new live attenuated mumps vaccine.

To develop a new live attenuated mumps vaccine, a wild mumps Y7 strain isolated from a patient who developed mild parotitis was treated with nitrosoguanidine and ultraviolet, followed by selection of a temperature-sensitive clone. The selected clone, Y125, showed stable temperature-sensitivity in Vero cells. Intraspinal inoculation of marmosets with the Y125 produced only minimal histopathological changes, while intracerebral inoculation of neonatal rats revealed that the Y125 did not cause hydrocephalus. Both these effects of the Y125 were similar to those of the non-neurovirulent Jeryl Lynn strain. Furthermore, subcutaneous inoculation of the Y125 induced high levels of neutralizing antibodies in all Cercopithecus monkeys examined. Although the safety and immunogenicity should be confirmed in further field trials in humans, the present results indicate that the Y125 could be a promising vaccine candidate.

Animals↗
PubMed2006

Phenobarbital induces monkey brain CYP2E1 protein but not hepatic CYP2E1, in vitro or in vivo chlorzoxazone metabolism.

Cytochrome P450 2E1 (CYP2E1) is expressed in the brain and liver, and can metabolize clinical drugs and activate toxins. The effect of phenobarbital on hepatic and brain CYP2E1 is unclear. We investigated the effect of chronic phenobarbital treatment on in vivo chlorzoxazone disposition (a CYP2E1 probe drug), in vitro chlorzoxazone metabolism, and hepatic and brain CYP2E1 protein levels in African Green monkeys (Cercopithecus aethiops). Monkeys were given oral saccharine or saccharine supplemented with 20 mg/kg phenobarbital (N = 6/group) for 22 days. Phenobarbital did not induce in vivo chlorzoxazone disposition, in vitro chlorzoxazone metabolism or hepatic CYP2E1 protein levels (all P > 0.05). However, phenobarbital induced brain CYP2E1 protein levels, using immunoblotting, by 1.26-fold in the cerebellum (P = 0.01) and 1.46-fold in the putamen (P = 0.04). Phenobarbital also increased cell-specific CYP2E1 expression, for example in the frontal cortical pyramidal neurons and cerebellar Purkinje cells. This data indicates that phenobarbital does not alter hepatic metabolism, but may alter metabolism of CYP2E1 substrates within the brain.

Administration, Oral↗
PubMed2006

Serum cytokines of the 20 Krad-irradiated S. mansoni cercariae vaccinated, primary and superinfected Cercopethicus aethiops aethiops.

Appropriate animal models are necessary to better understand the immune response in schistosomiasis. Schistosoma mansoni infection was established using irradiated cercariae in Cercopithecus aethiops aethiops (Grivet monkey) to describe immune responses of the serum cytokines, IL-4, IL-10, IL-12, IFN- gamma, and TNF-alpha. Intraperitoneal irradiated cercariae immunization on three occasions resulted in some differences of cytokine production. In primary infection, IL-4 was significantly raised (p=0.03) in the immunized monkeys, and there was an insignificant increase (p>0.05) in IL-10. However, ova excretion did not influence the cytokines, except in the controls where both IL-4 and IL-10 were significantly increased (p<0.05). In the controls, IL-12 and INF-gamma levels were lower after ova excretion, but the inflammatory TNF-alpha increased (p=0.049) and these findings can be associated with more liver pathogenesis in the group. Thus, this work has indicated the potential importance of anti-schistosome vaccine studies on the grivet monkeys.

Animals↗
PubMed2006

Phylogeny of primate T lymphotropic virus type 1 (PTLV-1) including various new Asian and African non-human primate strains.

To further unravel intra- and interspecies PTLV-1 evolution in Asia and Africa, we phylogenetically analysed 15 new STLV-1 LTR and env sequences discovered in eight different Asian and African non-human primate species. We show that orang-utan STLV-1s form a tight, deeply branching monophyletic cluster between Asian STLV-1 macaque species clades, suggesting natural cross-species transmission. Novel viruses of Macaca maura, Macaca nigra and siamang cluster with other Sulawesian STLV-1s, demonstrating close relatedness among the STLV-1s in these insular species and suggesting cross-species transmission to a siamang in captivity. Viruses from Western chimpanzees and a Western lowland gorilla cluster within the HTLV-lb/STLV-1 clade, the latter close to a human strain, indicative of zoonosis. A new STLV-1 from Cercopithecus ascanius differs from the published STLV-Cas57, explainable by the existence of five geographically separated subspecies. Barbary macaques, not yet described to be STLV-infected, carry a relatively recent acquired, typical African STLV-1, giving us no clue on the phylogeographical origin of PTLV-1.

Africa↗
PubMed2005

CYP2B6 is expressed in African Green monkey brain and is induced by chronic nicotine treatment.

CYP2B6 is a drug-metabolizing enzyme expressed in human tissues that can activate bupropion (a smoking cessation drug) and tobacco smoke nitrosamines and can inactivate drugs such as nicotine. Smokers have higher brain CYP2B6 protein levels compared to non-smokers but the cause of this elevation is unknown. We investigated the basal expression and the effect of chronic nicotine treatment on CYP2B6 protein in African Green monkey (Cercopithecus aethiops) brain. Basal expression of brain CYP2B6 was strong in specific cells such as the frontal cortical pyramidal cells, the cerebellar Purkinje cells and the neurons in the substantia nigra. Basal CYP2B6 protein levels varied 2.7-fold (non-significant) among 12 brain regions. All monkeys were given a subcutaneous 0.1 mg/kg nicotine test dose prior to treatment and the maximum plasma concentration achieved was 87 +/- 69 ng/ml and the half-life was 2.6 +/- 1.5 h. Monkeys were treated subcutaneously twice daily with nicotine at 0.05 mg/kg for 2 days, 0.15 mg/kg for 2 days followed by 0.3 mg/kg for 18 days (n = 6) or saline (n = 6). Chronic nicotine treatment induced CYP2B6 expression in specific cells such as astrocytes and neurons in the frontal cortex, caudate, thalamus and hippocampus. CYP2B6 protein levels were induced 1.5-fold in the frontal cortex (p < 0.01). Hepatic CYP2B6 expression was not altered by nicotine. In conclusion, CYP2B6 protein is expressed in specific cells in monkey brain and is induced by chronic nicotine treatment which may impact central metabolism of CYP2B6 substrates such as bupropion and nicotine.

Animals↗
PubMed2005

Vpu-mediated CD4 down-regulation and degradation is conserved among highly divergent SIV(cpz) strains.

Human immunodeficiency virus type 1 (HIV-1) along with simian immunodeficiency viruses from chimpanzees (SIV(cpz)) and three species of Old World monkeys from the genus Cercopithecus have been shown to encode a Vpu protein. To date, the functional characterization of Vpu has been limited to a small number of subtype B and more recently subtype C Vpu proteins. Using a recently developed VpuEGFP reporter system, we have shown that the subtype B and C Vpus are capable of preventing CD4 from being expressed on the cell surface. Using the same reporter system, we report here on the expression and functional analysis of Vpu protein from four SIV(cpz) isolates (CAM13, ANT, TAN1, and GAB1). All four SIV Vpu fusion proteins were efficiently expressed and prevented CD4 expression on the cell surface and induced CD4 degradation. This was surprising as three of the SIV(cpz) Vpu fusion proteins had only one canonical casein kinase II (CK-II) site (CAM13, ANT, TAN1) while previous studies with laboratory adapted HXB2 had indicated that both CK-II sites were required for CD4 degradation. Both ANT and TAN1 Vpu sequences encoded five consecutive negatively charged amino acids residues following the only CKII site (SAIEEDEE for ANT; SGVEEDEE for TAN1). We thus explored the possibility that this stretch of negatively charged amino acids might substitute for the lack of second CK-II site. Substitution of the aspartic acid at position 61 and glutamic acid at position 63 in the SIV(cpz) ANT Vpu within with lysine residues abolished the ability of this protein to down-modulate cell surface expression of CD4. Similarly, change of a serine to an alanine residue following the single consensus CK-II site of the CAM13 Vpu (SGNESDGGEEE) abolished CD4-down-regulation, suggesting that this serine was phosphorylated in the absence of a canonical CK-II site. Our results indicate that the serine was required, suggesting that this serine was phosphorylated by CK-II or possibly another cellular kinase. Taken together, these results show for the first time that Vpu proteins from SIV(cpz) isolates, although quite diverse in sequence and predicted secondary structure from the HIV-1 subtype B protein, are capable of down-regulating CD4, which is one of the major functions of the HIV-1 protein.

Amino Acid Sequence↗
PubMed2006

The boundary of macaque rDNA is constituted by low-copy sequences conserved during evolution.

In Macaca mulatta, the single rDNA array is flanked by a patchwork of sequences including subregions of human Yp11.2, 4q35.2, and 10p15.3. This composite DNA region is characterized by unique or low-copy sequences, resembling a potentially transcribed region. The analysis of Cercopithecus aethiops, Presbytis cristata, and Hylobates lar suggests that this complex sequence organization could be shared by Old World monkey and lesser ape species. After the lesser apes/great apes divergence, the unique or nonduplicated DNA region underwent amplification and spreading, preferentially marking the p arm of acrocentric chromosomes bearing the rDNA. The molecular analysis of human acrocentric chromosomes revealed some extent of remodeling of the rDNA boundary: near the human NOR, a large 4q35.2 duplication partially resembles that found in MMU; conversely, infrequently represented Yp11.2 sequences totally differed from those of the macaque, and 10p15.3 sequences were lacking. Thus, although evolutionary events modified the sequence organization of the MMU rDNA boundary, its overall sequence feature and the preferential location in vicinity to the NOR have been conserved.

Animals↗
PubMedDate not supplied

The effect of a single gavage dose of fumonisin B(1) on the sphinganine and sphingosine levels in vervet monkeys.

This is the first report of sphinganine (Sa) and sphingosine (So) levels determined in serum and urine of vervet monkeys (Cercopithecus aethiops) dosed with pure fumonisin B(1) (FB(1)). Initially, experimental vervet monkeys were given a single gavage dose of either 1 or 10 mg FB(1) /kg body weight. Blood and urine were sampled daily and on day seven the monkeys were terminated and the kidneys and livers harvested. In a subsequent experiment, other vervet monkeys were similarly dosed and blood and urine samples were collected over a 50-day period. In the high-dose monkeys the serum Sa/So ratio, as well as levels of serum cholesterol and liver function enzymes, increased during the first week after dosing and remained elevated for several weeks thereafter. The urinary Sa/So ratio and the serum renal function indicators showed a more rapid response and a correspondingly more rapid return to pre-dosing levels. In the low-dose monkeys serum Sa and the Sa/So ratio were the only parameters to increase above the control levels. The Sa/So ratio in liver and kidney tissue showed an elevation over controls in a dose-dependent manner. The serum Sa/So ratio was exclusively elevated above the control levels in the low- and high-dose monkeys and seems more relevant as a marker for fumonisin exposure than any of the other indicators.

Administration, Oral↗
PubMed2001

The effect of repeated gavage doses of fumonisin B1 on the sphinganine and sphingosine levels in vervet monkeys.

Fumonisins occur widely around the world in maize products intended for human and animal consumption posing a health hazard. Direct measurement of fumonisins in physiological fluids as a biomarker of exposure is not practicable, however fumonisins disrupt sphingoid metabolism by inhibition of sphinganine N-acyltransferase. In this study the disruption in sphinganine (Sa) and sphingosine (So) levels in plasma and urine was measured in vervet monkeys (Cercopithecus aethiops) dosed with repeated gavages of 1mg fumonisin B1 (FB1)/kg body weight three times/week continuously over a 51-day period. The plasma Sa/So ratio reached a maximum (mean of 4.3) after 30 days in the dosed monkeys with a three-fold increase above the ratio of the control monkeys and then declined slowly to double the value in controls after 51 days. The lack of a clear elevation in urinary Sa/So ratios after 51 days of multiple exposure in the dosed monkeys indicates that the plasma ratio is more sensitive than urinary changes in monkeys. This is confirmed by the plasma levels of liver function enzymes of which aspartate transaminase, glutamyl-transferase and lactate dehydrogenase were increased in the dosed monkeys, while the plasma indicators of renal function were not increased above the levels in the control monkeys. Thus repeated low doses of FB1 can cause sustained disruption of sphingoid metabolism.

Animals↗
PubMed2003

Taphonomic aspects of crowned hawk-eagle predation on monkeys.

This study provides a taphonomic analysis of prey accumulations of crowned hawk-eagles (Stephanoaetus coronatus) from Ngogo, Kibale National Park, Uganda, collected over 37 months from below nests of two eagle pairs. Crowned hawk-eagles are powerful predators capable of killing animals much larger than themselves, and are significant predators of cercopithecoid monkeys in forest habitats throughout sub-Saharan Africa. At Ngogo, 81% of the individuals in the kill sample are monkeys. Redtail monkeys (Cercopithecus ascanius) are particularly well represented in the sample, making up 66% of monkeys identified to species. Despite an impressive killing apparatus, crowned hawk-eagles are fastidious eaters that inflict far less damage to bone than mammalian predators. Examination of skeletal material from the Ngogo kill sample reveals that crania, hindlimb elements, and scapulae survive predation better than do other bones. Crania of adults are typically complete and accompanied by mandibles, while crania of young individuals are usually dissociated from mandibles and lack basicrania and faces. Long bones are often whole or show minimal damage. Thin bones, such as crania and innominates, are marked by numerous nicks, punctures, and "can-opener" perforations. Scapular blades are heavily raked and shattered. Along with the strong preference for cercopithecoids, these distinct patterns of bone survival and damage indicate the feasibility of recognizing specific taphonomic signatures of large raptors in fossil assemblages. Berger and Clarke (1995) hypothesized that crowned hawk-eagles or similar large raptors were principally responsible for the accumulation of the late Pliocene fossil fauna from Taung, South Africa, including the type infant skull of Australopithecus africanus. The results of our study suggest that the faunal composition and type of damage to the hominid skull and other bone from Taung are consistent with the predatory activities of large raptors. More rigorous assessment of their hypothesis will require sorting the Taung fauna by locality and further detailed analysis of species composition and bone damage and survivability patterns.

Animals↗
PubMed2000

Dynamic changes in cerebral glucose metabolism in conscious infant monkeys during the first year of life as measured by positron emission tomography.

Recently, advances in spatial resolution have provided the opportunity to utilize positron emission tomography (PET) to examine local cerebral metabolic rates for glucose (lCMR(glc)) in large animals noninvasively, thereby allowing repeated lCMR(glc) measurements in the same animal. Previous studies have attempted to describe the ontogeny of cerebral glucose metabolism in anesthetized nonhuman primates using [18F]fluorodeoxyglucose (FDG) and PET. However, the use of sedation during the tracer uptake period may influence lCMR(glc). This study was conducted to describe lCMR(glc) in conscious infant vervet monkeys (Cercopithecus aethiops sabaeus) during the first year of life utilizing FDG-PET. Cross-sectional studies (n=23) displayed lowest and highest lCMR(glc) in all structures at the 2-3 and 8-9 month age groups, respectively. The metabolic pattern suggested an increase in lCMR(glc) values between 2 and 8 months of age with decreased metabolism observed at 10-12 months of age in all regions. Peak lCMR(glc) values at 8 months were an average of 84+/-24% higher than values seen at the youngest age examined quantitatively (2-3 months). The regions of greatest and smallest increases in lCMR(glc) at 8 months were the cerebellar hemispheres (90%) and the thalamus (39%), respectively. Longitudinal analysis in 4 animals supported this developmental pattern, demonstrating the ability to detect changes in cerebral glucose metabolism within animals and the potential for FDG-PET in nonhuman primate models of brain maturation. By determining the normative profile of lCMR(glc) during development in monkeys, future application of FDG-PET will provide the opportunity to longitudinally assess the effects of environmental or pharmacological intervention on the immature brain.

Aging↗
PubMed2003

Visuomotor deficits and fast recovery after area V6A lesion in monkeys.

In order to study the involvement of area V6A in visually guided behavior, restricted lesions to the anterior bank of the parieto-occipital sulcus (POs) were made in two adult Cercopithecus aethiops monkeys, trained in visuomotor tests. Beside the known clinical signs of parietal deficit (abnormal posture of the arm contralateral to the most recent lesion and reluctance to use it), misreaching was evident soon after surgery and disappeared quickly. Uncertainties in a landmark test and prolonged response times to the pressing of light-buttons lasted for a few weeks and 1 month, respectively. As suggested by previous anatomical and physiological data, these findings confirm the role of the POs region in the execution of reaching movements. Moreover, they also demonstrate that following lesion, locally networked areas can rapidly adjust in order to re-establish pre-lesional behavior. These adjustments take place well before that any anatomical changes may occur.

Animals↗
PubMed2002

The recombinant chimeric human parainfluenza virus type 1 vaccine candidate, rHPIV3-1cp45, is attenuated, immunogenic, and protective in African green monkeys.

A recombinant live-attenuated chimeric human parainfluenza virus type 1 (HPIV1) candidate vaccine was previously generated by replacing the fusion (F) and hemagglutinin-neuraminidase (HN) glycoprotein open reading frames (ORFs) of the HPIV3 candidate vaccine, rHPIV3cp45, with those of wild-type HPIV1. Previously, this recombinant chimeric virus, designated rHPIV3-1cp45, exhibited a greater level of the temperature sensitivity of replication in vitro and a greater level of attenuation of replication in the respiratory tract of immunized hamsters when compared to its HPIV3cp45 parent virus. In the present study, rHPIV3-1cp45 was evaluated for its level of attenuation and efficacy in African green monkeys (Cercopithecus aethiops), a primate in which both HPIV1 and HPIV3 wild-type viruses replicate efficiently. The rHPIV3-1cp45 candidate vaccine was as restricted in replication in the upper and lower respiratory tract as its thoroughly characterized rHPIV3cp45 parent indicating that the attenuating mutations present in the rHPIV3cp45 backbone specified an appropriate level of attenuation of rHPIV3-1cp45 for primates. The level to which rHPIV3-1cp45 replicated in the respiratory tract of African green monkeys was also sufficient to induce a strong immune response to HPIV1 and provided protection against challenge with wild-type HPIV1. These results provide a basis for further evaluation of this HPIV1 candidate vaccine in humans.

Animals↗
PubMed1997

Intranasal Sendai virus vaccine protects African green monkeys from infection with human parainfluenza virus-type one.

Human parainfluenza virus-type I (hPIV-1) infections are a common cause of "group" and hospitalizations among young children. Here we address the possibility of using the xenotropic Sendai virus [a mouse parainfluenza virus (PIV)] as a vaccine for hPIV-1. Sendai virus was administered to six African green monkeys (Cercopithecus aethiops) by the intranasal (i.n.) route. A long lasting virus-specific antibody response was elicited, both in the serum and nasal cavity. Sendai virus caused no apparent clinical symptoms in the primates, but live virus was detected in the nasal cavity for several days after inoculation. No virus was detected after a second dose of Sendai virus was administered on day 126 after the initial priming. Animals were challenged with hPIV-1 i.n. on day 154. All six vaccinated animals were fully protected from infection while six of six control animals were infected with hPIV-1. The antibody responses induced by Sendai virus immunizations proved to be greater than those induced by hPIV-1. These results demonstrate that unmanipulated Sendai virus is an effective vaccine against hPIV-1 in a primate model and may constitute a practical vaccine for human use.

Administration, Intranasal↗
PubMed1996

Strain gauge analysis of the frontozygomatic region of the zygomatic complex.

PURPOSE: This study evaluates the biomechanical consequences of physiologic forces acting on the frontozygomatic suture region, with the ultimate goal of defining appropriate fixation techniques and improving the surgical management of this complex anatomic region. MATERIALS AND METHODS: Single foil strain gauges were bonded to the cortical surface of the frontal process of the zygoma in 13 subadult Cercopithecus africanus. Subdermal electrodes were used to induce tetanic contractions of the jaw elevator muscles, and bite force was measured using a twin-beam bite force transducer placed between the teeth. Microstrain was simultaneously measured and recorded. RESULTS: Tensile strains predominated in the region of the frontal process of the zygoma, with balancing side strains twice as large as working side strains; incisal strains were intermediate. CONCLUSIONS: The tensile strains observed in the frontozygomatic region contradict the concept of this area as a "stress riser" for compressive occlusal forces, and supports the use of compression plate osteosynthesis for improved stabilization of fractures in this region.

Animals↗