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PubMed2001

Assessing chronic exposure to fumonisin mycotoxins: the use of hair as a suitable noninvasive matrix.

This study describes for the first time the accumulation of measurable levels of fumonisin mycotoxins in the hair of nonhuman primates (vervet monkeys, Cercopithecus aethiops) and rats exposed to contaminated feed. Hair was subjected to reflux with methanol, and the resulting extract was cleaned up on strong anion exchange (SAX) and C18 solid-phase sorbents. Fumonisins FB1, FB2, and FB3 as well as their hydrolysis products commonly known as aminopolyols, AP1 and AP2, were detected in monkey hair using high-performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC-ESI-MS). Despite matrix interferences, the two-stage mass spectrometric process (MS-MS) yielded product ion mass spectra, which served as diagnostic indicators thus providing unequivocal identification of FB1, FB2, and FB3 as well as AP1 and AP2. In vervet monkeys, the levels of exposure related well to the levels of toxin detected in hair, and levels as high as 5.98 mg FB1, 33.77 mg FB1, and 65.93 mg FB1/kg of hair were found in monkeys receiving control, low-dose, and high-dose contaminated diets, respectively. Hair was also analyzed from rats given either single gavage doses of 1 and 10 mg FB1/kg body weight or contaminated feed (50 mg FB1/kg), resulting in an exposure of approximately 4.25 mg FB1/kg body weight/day based on the measured daily feed intake. Analysis of rat hair over a four-week period indicated that mean levels up to 34.50 mg/kg and 42.20 mg/kg were detectable by the fourth week in the rats treated by gavage (10 mg FB1/kg body weight) and those receiving contaminated feed, respectively. This relationship indicates that hair can provide an easily applicable non-invasive matrix for assessing chronic exposure to fumonisin mycotoxins.

Administration, Oral↗
PubMed1987

Intestinal structural changes in African green monkeys after long term psyllium or cellulose feeding.

Intestinal structure of male adult African Green monkeys (Cercopithecus aethiops ssp vervets) was studied after 3 1/2 yr of consuming diets containing 10% psyllium husk or cellulose. Scanning electron microscopy (SEM) identified mild damage (cellular swelling and disarray, and microvillar denudation and disarray) at villous tips throughout the small intestine in the psyllium-fed monkeys. The cellulose group had similar duodenal damage. Differences were not found in colons by SEM. By light microscopy, jejunum had shorter villi with psyllium feeding, based upon villous height (P less than 0.05), and length around a sectioned villus (P less than 0.1), but not based upon the number of enterocytes per villus. Jejunal and ileal circular and longitudinal muscle layer thicknesses were increased in psyllium-fed monkeys. Colonic mucosal height was significantly (P less than 0.05) reduced and muscle layer thickness was mildly reduced in the psyllium-fed monkeys. Group differences were not found in intestinal weight or length or in the weight of small intestinal mucosal scrapings. Psyllium husk may cause epithelial cell loss and muscle layer hypertrophy in the jejunum and ileum and thinning of the colonic wall after prolonged feeding.

Animals↗
PubMed1978

Cae I: an endonuclease isolated from the African green monkey with properties indicating site-specific cleavage of homologous and heterologous mammalian DNA.

Component alpha DNA is a highly repetitive sequence that comprises nearly a quarter of the African green monkey (Cercopithecus aethiops) genome. A previous microbial restriction enzyme analysis showed that the repeat structure of component alpha DNA is based upon a monomeric unit of 176 +/- 4 base-pairs. An endonuclease, provisionally termed Case I, has been isolated from African green monkey testes that cleaves component alpha DNA into multimeric segments based upon the same repeat periodicity as that revealed by microbial restriction enzymes. The primary sites of Cae I cleavage in the component alpha sequence appear to be 120 +/- 6 base-pairs distant from the Hind III sites and 73 +/- 6 base-pairs distant from the Eco RI* sites. Cae I has been partially characterized with special reference to the effects of ATP and S-adenosylmethionine on the cleavage of component alpha DNA. Cae I may be a member of a class of similar site-specific nucleases present in mammalian cells. Cae I also cleaves mouse satellite DNA into a multimeric series of discrete segments: the periodicity of this series is shorter than that revealed by Eco RII retriction analysis of mouse satellite DNA.

Adenosine Triphosphate↗
PubMed1993

Genetic variation of the SIVagm transmembrane glycoprotein in naturally and experimentally infected primates.

OBJECTIVE: An in-frame stop codon prematurely truncating the transmembrane glycoprotein (TMP) is a common feature of many simian immunodeficiency virus, African green monkey strain (SIVagm) molecular clones. The purpose of this study was to investigate the native form of the SIVagm TMP in a naturally infected African green monkey (AGM) and to study the fate of the stop codon following the passage of SIVagm in primates. DESIGN: Polymerase chain reaction was used to clone the entire intracellular portion of the TMP from: (1) peripheral blood mononuclear cells (PBMC) of the naturally infected AGM 155; (2) an isolate of SIVagm155 in rhesus PBMC and (3) PBMC from pig-tailed macaques and AGM experimentally infected with an SIVagm molecular clone encoding a truncated TMP. RESULTS: PBMC of the naturally infected AGM contained a 'swarm' of related virus genotypes that encoded a full-length TMP, whereas tissue-culture passage in rhesus PBMC resulted in a prematurely truncated form of the TMP. This premature stop codon persisted in PBMC of monkeys experimentally infected with an SIVagm molecular clone. Both macaques and AGM of same subspecies as AGM 155 (Cercopithecus pygerythrus) and other subspecies (C. aethiops and C. sabaeus) became infected with SIVagm155. Genetic drift of this region of env, as assessed by calculation of the nucleotide substitution/site/year rate, was similar to that of other retroviruses. CONCLUSIONS: The native form of the SIVagm TMP is a full-length gp40, similar to the SIV macaque (SIVmac) strain and HIV-1. However, passage of SIVagm in tissue culture can result in point mutations that introduce a premature stop codon. This stop codon persists during subsequent in vivo passage of SIVagm in primates. This contrasts with similar studies in macaques infected with SIVmac, in which reversion of the TMP stop codon was observed.

Amino Acid Sequence↗
PubMed1998

Effects of large neutral amino acid concentrations on 6-[F-18]Fluoro-L-DOPA kinetics.

6-[F-18]Fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) has been used to measure the central dopaminergic function in many species, including humans and monkeys. For transport across the blood brain barrier (BBB), FDOPA competes with plasma large neutral amino acids (LNAA). In this article we evaluate the effects of normal physiological LNAA concentration variation on BBB transport (K1) and the FDOPA uptake measurement, Ki. We also investigate a method for reducing the dependency of FDOPA quantitation on LNAA. Adult vervet monkeys (Cercopithecus aethiops sabaeus, n = 19) were fasted overnight before FDOPA positron emission tomography scans. Blood samples were drawn for LNAA determination, metabolite analysis, and compartmental modeling. The estimated K1 and Ki were both negatively correlated with LNAA concentrations (r2 = 0.51 and 0.62, respectively). Using an adjustment to K1 and Ki based on these correlations, the LNAA dependency was reduced (SD of the data for K1 was reduced by 33%, for Ki by 40%). Experiments with amino acid loading on an additional six animals indicate that BBB transport can be described using Michaelis-Menten kinetics. Results show a clear dependence of FDOPA uptake on plasma LNAA concentrations, which can be removed to increase the precision of FDOPA quantitation.

Amino Acids↗
PubMed1979

Implications for adult roles from differential styles of mother-infant bonding: an ethological study.

Ethological observations of maternal and infant behaviors of nine vervet monkey pairs (Cercopithecus aethiops sabaeus) showed the effects of differential styles of early maternal responsiveness on later infant competence. Those infants receiving the least amount of maternal responsiveness and the most time-off the mother in the first 3 months of development were more socially competent at 6 months of age. The results are discussed within current ethological "attachment" theories. The detachment or separation process of mother-infant interaction is considered as important a factor during infant development as the primary maternal bond.

Animals↗
PubMed1983

Apparent hallucinations in monkeys during around-the-clock amphetamine for seven to fourteen days. Possible relevance to amphetamine psychosis.

Schizophrenia-like symptoms have been experimentally produced in humans by a single, large dose of amphetamine or by relatively low level, but continuous administration of the drug. In animal studies of the psychotomimetic properties of amphetamine, high doses and, in particular, repeated daily-injection drug schedules have often been used. However, amphetamine psychosis is not always a prominent effect of repeated intake drug schedules in humans and available clinical evidence suggests that psychosis develops more readily when the drug is taken in a continuous fashion over longer periods. The state produced by single large doses of amphetamine, although clearly abnormal, has been said to bear less resemblance to schizophrenia than the delayed paranoid symptoms developing after longer periods of continuous intake. In the present experiments we have studied the behavioral effects of 7 to 14 days of continuous administration of amphetamine to monkeys (Cercopithecus aethiops) using subcutaneously implanted silicone capsules releasing approximately .7 to 1.5 mg/kg/day of d-amphetamine base. Around-the-clock TV monitoring of the animals revealed a general biphasic sequence of drug effects, although considerable individual variation occurred: a) an "acute" phase dominated by stereotyped movements and/or prolonged staring, lasting for 2 to 5 days; b) a "late" phase peaking during days 5 to 10 after capsule implantation and characterized by highly individual, but striking sequences of: (1) Attack or sudden threat reactions directed at invisible objects; (2) rapid orienting and flight behavior without apparent cause; (3) sudden startle reactions; (4) prolonged vocalization; (5) visual tracking of invisible objects, sometimes involving coordinated patterns of "eating behavior" and (6) prolonged and rapid grooming directed at various parts of the body. These behaviors might be termed "hallucinatory" since no eliciting stimuli could be determined for their occurrence. Motor disturbances, including whole-body shakes, were often present at the same time. The animals were generally sleepless throughout the drug treatment period. Reimplantation of amphetamine capsules 2 to 8 months after the first capsule treatment produced the same effects in an individual-specific manner, but the "late phase" behaviors generally appeared sooner. The delayed occurrence of apparent hallucinatory behaviors and other abnormal "late" phase behaviors in the present experiment may be a close parallel to the delayed development of psychosis in humans induced by a similar drug regimen. Furthermore, the hallucinogenic nature of the late amphetamine state is consonant with other reports in the literature that hallucinogen-characteristic behaviors are present at this time.

Animals↗
PubMed1996

Sequence variation and subtyping of human and simian T-cell lymphotropic virus type I strains from South Africa.

We report on the subtyping of South African primate T-cell lymphotropic virus type I (PTLV-I) strains by investigating the LTR region using sequence analysis and restriction fragment length polymorphism (RFLP) techniques. DNA from either uncultured peripheral blood mononuclear cells (PBMCs); cultured PBMC or cell lines of eight human T-cell lymphotropic virus type I (HTLV-I); and two simian T-cell lymphotropic virus type I (STLV-I) strains (Cercopithecus aethiops pygerythrus) were amplified by polymerase chain reaction (PCR), cloned, and sequenced. The samples originated from different geographical regions in South Africa. Phylogenetic relationships were estimated using the neighbor-joining method. The South African HTLV-I strains were of Cosmopolitan origin and similar to each other. RFLP analysis confirmed this subtyping. A divergence of 0.3 to 1.6% between the Cosmopolitan strains was observed, while the divergence between the HTLV-I and STLV-I strains ranged from 6.3 to 7%. The STLV-I strains were closely related to that of a chimpanzee, providing evidence of interspecies transmission.

Animals↗
PubMed2007

The association of DRD4 and novelty seeking is found in a nonhuman primate model.

OBJECTIVE: The association of novelty seeking with a repeat polymorphism in the coding region of the dopamine D4 receptor gene (DRD4) has been demonstrated in several human populations, but not in others. The objective of this study was to test the generality of the association in a captive nonhuman primate population of known history, using objective methods for assessing novelty seeking and a pedigree-based association design. METHODS: Four hundred and fifty two socially-living vervet monkeys (Cercopithecus aethiops) from a large multigenerational pedigree at the UCLA-VA Vervet Research Colony were studied. Two variants in the 48 base pair repeat in exon III of the DRD4 gene have been found in this population, a six-repeat (92%) and a less common five-repeat (8%). Novelty seeking was measured by the latency to approach a large and potentially threatening novel object placed in the home enclosure. Heritability of novelty seeking and the association of novelty seeking with the DRD4 polymorphism were assessed using variance component modeling as implemented in Sequential Oligogenic Linkage Analysis Routines. RESULTS: The variance component analysis indicated that the DRD4 variant explained a significant portion of the total variance in novelty seeking. The final model included a significant effect of the DRD4 polymorphism (P=0.03), which explained 13% of the phenotypic variance, and a significant remaining genetic effect (h=0. 467+/-0.095, P<0.0001). CONCLUSIONS: The association of DRD4 with novelty seeking has now been replicated in a nonhuman primate species, the vervet monkey.

Analysis of Variance↗
PubMed1997

The formation of red colobus-diana monkey associations under predation pressure from chimpanzees.

It is generally assumed that most primates live in monospecific or polyspecific groups because group living provides protection against predation, but hard evidence is scarce. We tested the antipredation hypothesis with observational and experimental data on mixed-species groups of red colobus (Procolobus badius) and diana monkeys (Cercopithecus diana) in the Taï National Park, Ivory Coast. Red colobus, but not diana monkeys, are frequently killed by cooperatively hunting chimpanzees. Association rates peaked during the chimpanzees' hunting season, as a result of changes in the behaviour of the red colobus. In addition, playbacks of recordings of chimpanzee sounds induced the formation of new associations and extended the duration of existing associations. No such effects were observed in reaction to control experiments and playbacks of leopard recordings.

Animals↗
PubMed2006

Vervet monkeys and humans show brain asymmetries for processing conspecific vocalizations, but with opposite patterns of laterality.

A robust finding in the human neurosciences is the observation of a left hemisphere specialization for processing spoken language. Previous studies suggest that this auditory specialization and brain asymmetry derive from a primate ancestor. Most of these studies focus on the genus Macaca and all demonstrate a left hemisphere bias. Due to the narrow taxonomic scope, however, we lack a sense of the distribution of this asymmetry among primates. Further, although the left hemisphere bias appears mediated by conspecific calls, other possibilities exist including familiarity, emotional relevance and more general acoustic properties of the signal. To broaden the taxonomic scope and test the specificity of the apparent hemisphere bias, we conducted an experiment on vervets (Cercopithecus aethiops)-a different genus of old world monkeys and implemented the relevant acoustic controls. Using the same head orienting procedure tested with macaques, results show a strong left ear/right hemisphere bias for conspecific vocalizations (both familiar and unfamiliar), but no asymmetry for other primate vocalizations or non-biological sounds. These results suggest that although auditory asymmetries for processing species-specific vocalizations are a common feature of the primate brain, the direction of this asymmetry may be relatively plastic. This finding raises significant questions for how ontogenetic and evolutionary forces have impacted on primate brain evolution.

Animals↗
PubMed1998

Simian immunodeficiency viruses (SIVs) from eastern and southern Africa: detection of a SIVagm variant from a chacma baboon.

Simian immunodeficiency viruses (SIVs) have been shown to infect many Old World African primate species. Thus far, no work has been published on southern African primates. In this study we investigated the genetic diversity between SIV strains from Kenyan and South African vervets (Cercopithecus aethiops pygerythrus). We amplified and sequenced a 1113 bp region of the env gene. Phylogenetic analysis of these sequences showed that all strains clustered with members of the vervet subgroup of SIVagm. The SIVs from South African vervets differed by 7% from each other and by 8-14% from the Kenyan SIV strains, while the Kenyan SIV strains differed by 10-21% from SIVagm of other east African vervets. We also isolated and sequenced, for the first time, a SIV strain from a healthy chacma baboon (Papio ursinus), caught in South Africa. Phylogenetic analysis of the env region showed the virus to be closely related to the South African vervet SIV strains, while analysis of its pol region confirmed the virus to be a SIVagm variant.

Amino Acid Sequence↗
PubMed2004

Disruption of self-organized actions in monkeys with progressive MPTP-induced parkinsonism. I. Effects of task complexity.

Parkinson's disease (PD) is characterized by motor symptoms, usually accompanied by cognitive deficits. The question addressed in this study is whether complexity of routine actions can exacerbate parkinsonian disorders that are often considered to be motor symptoms. To examine this question, we trained four vervet monkeys (Cercopithecus aethiops) to perform three multiple-choice retrieval tasks. In order of ascending complexity, rewards were freely available (task 1), covered with transparent sliding plaques (task 2), and covered with opaque sliding plaques cued by symbols (task 3). Thus, from task 1 to task 2 we added a motor difficulty--the recall of context-adapted movement; and from task 2 to task 3 we added a cognitive difficulty: the recall of symbol-reward associations. The more complex the task, the longer it took to learn, but after extensive training the performance was stable in all tasks, with similar retrieval durations. The monkeys then received systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injections (0.3-0.4 mg/kg) every 4-7 days, until the first motor symptoms appeared. In the course of MPTP intoxication, the behavioural performance declined while the motor symptoms were absent or mild--the retrieval duration increased, and non-initiated choices and hesitations between choices became frequent. Interestingly, this decline was in proportion to task complexity, and was particularly pronounced with the cognitive difficulty. Furthermore, freezing appeared only with the cognitive difficulty. We therefore suggest that everyday cognitive difficulties may exacerbate hypokinesia (lack of initiation, abnormal slowness) and executive disorders (hesitations, freezing) in the early stages of human PD.

Animals↗
PubMed2004

Disruption of self-organized actions in monkeys with progressive MPTP-induced parkinsonism: II. Effects of reward preference.

The motor and cognitive symptoms of Parkinson's disease (PD) are well documented, but little is known about the functionality of motivational processes mediated by the limbic circuits of basal ganglia. The aim of this study was to test the ability of motivational processes to direct and to urge behaviour, in four vervet monkeys (Cercopithecus aethiops) progressively intoxicated with systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injections (0.3-0.4 mg/kg every 4-7 days). In the food preference task, the monkeys had to retrieve two types of directly visible food, simultaneously available in the wells of a reward board. At all stages of MPTP-induced parkinsonism, the monkeys continued to take their favourite food first. In the symbol discrimination task, the wells were covered with sliding plaques cued by symbols indicating the absence or presence of a reward, and the different types of food were blocked in separate sessions. Monkeys with mild or moderate parkinsonism made fewer attempts and took longer to retrieve non-preferred compared with preferred rewards. These results indicate that motivational processes are still able to direct (food preference task) and to urge (symbol discrimination task) behaviour in MPTP-lesioned monkeys. Such a functional preservation may be related to the relatively spared dopaminergic innervation of the limbic circuits that we found in our monkeys, in agreement with the literature on humans. Furthermore, the frequency of executive disorders (such as hesitations and freezing) appeared to be much lower with the preferred rewards. Thus, the preserved motivational processes may help to overcome executive dysfunction in the early stages of human PD.

Animals↗
PubMed1986

A field study of infection with human T-cell leukemia virus among African primates.

African non-human primates were surveyed seroepidemiologically for natural infection of human T-cell leukemia virus type I (ATLV/HTLV-I) or its closely related virus(es). Materials from three genera (Cercopithecus, Papio, and Theropithecus), four species (grivet monkey, Anubis baboon, Hamadryas baboon, and gelada), totalling 983 animals under natural conditions, were obtained in a field study in Ethiopia. Virus infection was determined by the indirect immunofluorescence test using HTLV-I specific antigens. Animals seropositive for HTLV-I were found among grivet monkeys and Anubis baboons including the hybrid offspring between Anubis and Hamadryas baboons but not pure-Hamadryas baboons and geladas. From these results, the HTLV-I family was proved to be widespread on the African continent and was regarded as a common retrovirus among catarrhines.

Animals↗
PubMed1985

The pulpal response to dilute citric acid smear removers.

The aim of this study was to determine the pulpal response to three dilute citric acid smear removers. Forty-eight vervet monkeys (Cercopithecus aethiops pygerythrus), in three groups of sixteen animals provided 384 tooth specimens for the histological evaluation of the pulpal response at 3, 31, and 59 days post-operatively. Labial Class V cavities were prepared in the maxillary and mandibular incisor teeth. The pulpal responses elicited by 1% aqueous citric acid, 1% citric acid in 30% ethanol and 0.1% citric acid in 30% ethanol solutions, in unlined cavities and in cavities lined with Dycal after acid application, were compared with those elicited by a negative control material--(Nobetec), and a positive control material--(Syntrex). Using Stanley's criteria the most severe pulpal responses were seen in teeth treated with 1% aqueous citric acid and 1% citric acid in 30% ethanol without a subsequent liner, and by Syntrex at all three time intervals. The use of Dycal as a liner after smear removal markedly reduced the pulpal responses.

Acid Etching, Dental↗
PubMed2005

Subarachnoid injection of Microfil reveals connections between cerebrospinal fluid and nasal lymphatics in the non-human primate.

Based on quantitative and qualitative studies in a variety of mammalian species, it would appear that a significant portion of cerebrospinal fluid (CSF) drainage is associated with transport along cranial and spinal nerves with absorption taking place into lymphatic vessels external to the central nervous system. CSF appears to convect primarily through the cribriform plate into lymphatics associated with the submucosa of the olfactory and respiratory epithelium. However, the significance of this pathway for CSF absorption in primates has never been established unequivocally. In past studies, we infused Microfil into the subarachnoid compartment of numerous species to visualize CSF transport pathways. The success of this method encouraged us to use a similar approach in the non-human primate. Yellow Microfil was injected post mortem into the cisterna magna of 6 years old Barbados green monkeys (Cercopithecus aethiops sabeus, n = 6). Macroscopic and microscopic examination revealed that Microfil was (1) distributed throughout the subarachnoid compartment, (2) located in the perineurial spaces associated with the fila olfactoria, (3) present within the olfactory submucosa, and (4) situated within an extensive network of lymphatic vessels in the nasal submucosa, nasal septum and turbinate tissues. We conclude that the Microfil distribution patterns in the monkey were very similar to those observed in many other species suggesting that significant nasal lymphatic uptake of CSF occurs in the non-human primate.

Animals↗
PubMed1995

Visceral leishmaniasis in vervet monkeys: immunological responses during asymptomatic infections.

Nine vervet monkeys (Cercopithecus aethiops) were infected intradermally with 8 x 10(7) virulent L. donovani promastigotes. Four animals developed clinical visceral leishmaniasis and died over a period of 18 months. The remaining five animals have remained asymptomatic for a period of 3 years now. Attempts to isolate parasites from spleen and liver through biopsies were fruitless. Immunological responses of these subclinically infected animals were examined. Enzyme-linked immunosorbent assay (ELISA) and western blot analyses demonstrated Leishmania specific antibodies in these animals, but the antibody titres were low. When proliferation of peripheral blood monocytes (PBMC) to Concanavalin A (Con A) of these animals was compared with control 'disease free animals' there were no significant differences in response. However, L. donovani antigen (fixed promastigotes) specific proliferation was demonstrated in the five subclinically infected animals. High and varying levels of interferon gamma (IFN-gamma) were secreted in PBMC cultures from the five vervet monkeys when stimulated with either Con A or L. donovani antigens. In control animals, IFN-gamma was only detected when PBMC were stimulated with Con A. Marked delayed-type hypersensitivity (DTH) responses were demonstrated in the five subclinically infected animals 48 h after injection with formalin fixed promastgotes. It was concluded that the visceral Leishmania disease spectrum due to L. donovani observed in humans could be induced in vervet monkeys and that L. donovani asymptomatic/cryptic infected animals have competent humoral and cellular responses to homologous parasites.

Animals↗