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The transentorhinal cortex of the African green monkey: a combined light- and electron-microscopic study of calcium-binding protein containing neurons.

The transentorhinal cortex (TEC) is a primate-specific transition zone between the entorhinal allocortex and the temporal isocortex. Neurons in the lamina pre-alpha of TEC are known to be the first to develop intraneuronal changes in the course of Alzheimer's disease. In order to shed light on this important feature, we studied as yet unknown morphological and neurochemical characteristics of the TEC of the African green monkey (Cercopithecus aethiops sabaeus). Using light- and electron-microscopic immunocytochemistry, the distribution and morphology of neurons containing calcium-binding proteins were described and compared with those in the adjacent cortices. Light-microscopic analysis revealed that parvalbumin-containing neurons were distributed in all cortical layers. Calbindin-containing cells were fewer but also present in each layer. Calretinin-containing neurons were largely confined to the upper layers of the TEC. All three types of neuron showed pyramidal-like, multipolar and bipolar shapes; their dendrites were smooth or beaded. Ultrastructural studies revealed immunopositive somata with infolded nuclei and large amounts of cytoplasm. The somata were only sparsely innervated by symmetric synapses. Immunopositive dendrites were almost exclusively covered with immunonegative axon terminals establishing symmetric and asymmetric synapses. Immunopositive terminals established symmetric contacts with immunonegative dendrites and somata. Only occasionally, could synaptic contacts between immunopositive pre- and postsynaptic structures be observed. The comparison of neurons in the TEC and adjacent cortices revealed no striking differences. In summary, the morphological and neurochemical characteristics of TEC neurons as analyzed in our study do not provide an explanation for the early onset of neurodegenerative changes in the TEC.

Animals↗

Intradiscal application of hyaluronic acid in the non-human primate lumbar spine: radiological results.

Prospectively, with randomized segment-treatment assignment, and with blinded evaluators, lumbar motion segments in Cercopithecus monkeys were analyzed for macroscopic and radiological changes 24 weeks after nucleotomy and nucleotomy with additional intradiscal application of different hyaluronic acid formulations versus untreated control segments. The objective was to find out whether hyaluronic acid is able to influence the degenerative cascade in nonhuman primates after nucleotomy. In a similar procedure, hyaluronic acid has proven to decrease degeneration after nucleotomy in a Minipig model. This is the first such study ever undertaken in primates, thus trying to overcome the known limitations of non-primate spine models. Twenty monkeys with four segments each obtained nucleotomy in three segments and solely exposure of another control segment. Nucleotomy was performed from a transpsoatic retroperitoneal approach. Preoperative radiographs and follow-up radiographs, magnetic resonance imaging (MRI), computed tomography (CT), Q-CT with bone mineral density measurements and three-dimensional reconstruction were obtained and analyzed qualitatively and quantitatively. Segments with high-molecular-weight hyaluronic acid (Hylan G-F 20) application proved to be significantly superior over those with a standard nucleotomy in radiographs, MR images, CT scans, and macroscopic appearance at follow-up. Control segments remained unaffected. Interdependence between the different methods validated the utilized methods of quantitative radiological assessment of degeneration. Hylan G-F 20 appears to be a possible adjunct in reducing postoperative degeneration in an animal nucleotomy model. It deserves further evaluation, despite the fact that the mechanisms of its effects are still speculative.

Animals↗

Life-history parameters of a wild group of West African patas monkeys (Erythrocebus patas patas).

Based on long-term, although intermittent, observations (2 years 4 months of 14 years), we present data on birth seasonality, age at first birth, interbirth intervals, mortality rates, age at first emigration, and population change of a wild population of West African patas monkeys ( Etythrocebus patas patas) in northern Cameroon. Birth season was from the end of December until the middle of February, corresponding to the mid-dry season. In spite of large body size, the patas females had the earliest age at first birth (36.5 monthsold) and the shortest interbirth intervals (12 months) compared to the closely related wild forest guenons. Age at first emigration of the males was considered to occur between 2.5 and 4.5 years. The group size of the focal group drastically decreased between 1984 and 1987, and steadily increased until 1994, then decreased again in 1997. The neighboring group also showed a similar trend in group size. The population decreases were likely to be caused by drought over 3 years. Annual crude adult mortality rate was 4% during population increase periods (PIP) between 1987 and 1994. It rose to 22% during all the periods (AP), including drought over 3 years. Despite their smaller body size, the rate of the wild forest guenons ( Cercopithecus mitis) (4%) was the same and much lower than those of the patas during PIP and AP, respectively. The annual average juvenile mortality rate was 13% during PIP and it also rose to 37% during AP. That of wild forest guenons ( C. ascanius) (10-12%) was a little lower and much lower than those of the patas during PIP and AP, respectively. These findings were consistent with Charnov's theoretical model of mammalian life-history evolution in that patas with high adult and juvenile mortality showed early and frequent reproduction in spite of large body size. Charnov also considered high adult mortality as a selective force and high juvenile mortality as a density-dependent consequence of high fecundity. Our results support the former but not the latter research findings.

Age Factors↗

Leishmania aethiopica: experimental infections in non-human primates.

Six Cercopithecus aethiops monkeys, 4 Theropithecus gelada baboons and 2 Papio anubis baboons were infected using Leishmania aethiopica isolates originating either from localized (LCL) or diffuse (DCL) cutaneous leishmaniasis patients. The history of lesions in 4 C. aethiops monkeys infected by LCL strains mimicked the process in human LCL patients. Infection of 2 C. aethiops monkeys using a DCL strain resulted in localized, non-ulcerative, self-healing nodular lesions. Such lesions were also observed in 2 T. gelada baboons infected by LCL strains. Active lesions and healing in C. aethiops and T. gelada, after infection by LCL stains, were accompanied by positive DTH and immunity to challenge by LCL or DCL strains.

Animals↗

Glycosphingolipids of a green monkey kidney cell line (GMK AH-1). Evidence for a novel pentaglycosylceramide based on globotetraosylceramide.

Total non-acid glycolipid fractions have been isolated from GMK AH-1 cells grown in fetal calf serum and in horse serum. For comparison, glycolipids were also prepared from green monkey (Cercopithecus aetiops) kidney and from fetal calf serum. The major glycolipids from GMK AH-1 cells grown in fetal calf serum were isolated by silicic acid column chromatography and preparative thin-layer chromatography. These fractions were characterized mainly by thin-layer chromatography, mass spectrometry and gas chromatography. The structures of the glycolipids isolated were proposed as: Glc1 leads to 1Cer, Gal1 leads to 1Cer, Gal1 leads to 4Glc1 leads to 1Cer, Gal1 leads to 4Gal1 leads to 4Glc1 leads to 1Cer, GalNAcl leads to 3Gal1 leads to 4Gal1 leads 4Glc1 leads to 1Cer. In addition, a novel pentaglycosylceramide with the probable structure Ga1 beta 1 leads to 3GalNAc beta 1 leads to Gal alpha 1 leads to 4Gal beta 1 leads to 4Glc beta 1 leads to 1Cer was also present. THe ceramides contained mainly dihydroxy 18:1 long-chain base in combination with non-hydroxy 16:0-24:0 fatty acids. Small amounts of trihydroxy 18:0 long-chain base and hydroxy 22:0-24:0 fatty acids were also present in the mono- and diglycosylceramide fractions. The glycolipid patterns of GMK AH-1 cells grown in fetal calf serum or horse serum were identical. The pentaglycosylceramide present in the cultured cells could not be detected with certainty in the kidney tissue. The uptake of this glycolipid from the culture medium is unlikely as it seems to be lacking in calf serum.

Animals↗

Neocortical infarction in subhuman primates leads to restricted morphological damage of the cholinergic neurons in the nucleus basalis of Meynert.

The aim of the present study was to investigate the long-term effect of cortical infarction on the subhuman primate (Cercopithecus aethiops) basal forebrain. The lesion, carried out by cauterizing the pial blood vessels supplying the left fronto-parieto-temporal neocortex, induced retrograde degenerative processes within the ipsilateral nucleus basalis of Meynert. The morphometrical analysis revealed that significant shrinkage of cholinergic neurons and loss of neuritic processes were localized within the intermediate regions of the nucleus basalis. The average cross-sectional areas of choline acetyltransferase-immunoreactive neurons in the intermedio-ventral (Ch4iv) and intermedio-dorsal (Ch4id) nucleus basalis were decreased to 62.5 +/- 9.5 and 58.0 +/- 8.6%, respectively, of the sham-operated values. Although an apparent loss of Nissl-stained magnocellular neurons in Ch4iv and Ch4id was found by applying a quantitative analysis based on a perikaryal-size criterion, data obtained by the quantification of immunostained material failed to reveal any significant decrease of cholinergic cell density. Results are discussed in view of future application of this ischemic model to study processes of retrograde degeneration following cortical target removal and to assess potential neurotrophic and neuroprotective properties of pharmacologic agents.

Animals↗

NGF-mediated synaptic sprouting in the cerebral cortex of lesioned primate brain.

In the present study, coronal brain sections of cortically devascularized non-human primates (Cercopithecus aethiops) were used to assess the lesion-associated synaptic loss, and the effect of exogenous nerve growth factor (NGF) in preventing or reversing this neurodegeneration. The sections were immunolabeled with antibodies against the synaptic marker protein synaptophysin (SYN), as well as choline acetyltransferase (ChAT) and parvalbumin (PV) markers that identify cholinergic neurons and interneurons, respectively. We found that, compared to sham-operated animals, in the lesioned vehicle treated animals SYN immunoreactivity near the lesioned site in the frontoparietal cortex was decreased by 31%. Similarly, corrected optical density values of immunostained sections specific for ChAT in the nucleus basalis of Meynert (ipsilateral to the lesion) decreased by 20% and PV-immunoreactive neurons near the lesion decreased by 47%. In contrast, NGF-treated lesioned animals showed levels of SYN, ChAT, and PV immunoreactivity similar to sham controls. These results are consistent with previous studies and support the view that NGF may not only prevent neurodegenerative changes after neocortical infarction by protecting vulnerable neurons, but also is capable of inducing sprouting and synaptogenesis.

Animals↗

The representation of social relations by monkeys.

Monkeys recognize the social relations that exist among others in their group. They know who associates with whom, for example, and other animals' relative dominance ranks. In addition, monkeys appear to compare types of social relations and make same/different judgments about them. In captivity, longtailed macaques (Macaca fascicularis) trained to recognize the relation between one adult female and her offspring can identify the same relation among other mother-offspring pairs, and distinguish this relation from bonds between individuals who are related in a different way. In the wild, if a vervet monkey (Cercopithecus aethiops) has seen a fight between a member of its own family and a member of Family X, this increases the likelihood that it will act aggressively toward another member of Family X. Vervets act as if they recognize some similarity between their own close associates and the close associates of others. To make such comparisons the monkeys must have some way of representing the properties of social relationships. We discuss the adaptive value of such representations, the information they contain, their structure, and their limitations.

Animals↗

3,4-Dihydroxyphenylacetic acid and homovanillic acid in rat plasma: possible indicators of central dopaminergic activity.

The concentrations of dopamine (DA) metabolites (free and conjugated) was measured in plasma and brain regions of rats by the mass spectrometric method of selected ion monitoring. Experimental treatments which altered the function of central dopamine neurons also induced concomitant changes in plasma 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Stimulation of the nigrostriatal pathway increased plasma DOPAC and HVA whereas lesion of the pathway decreased plasma metabolites. Several drug treatments induced parallel changes in brain and plasma concentrations of DA metabolites. It is suggested that changes in the concentration of DOPAC and HVA in rat brain are reflected by parallel changes in plasma. No conjugated forms of DOPAC and HVA were found in plasma and brain tissue of vervet monkeys (Cercopithecus aethiops).

3,4-Dihydroxyphenylacetic Acid↗

Behavioral aspects of serotonin-dopamine interaction in the monkey.

The effects of serotonin (5-hydroxytryptamine; 5-HT) antagonists and 5-HT uptake inhibitors on the behavioral response to amphetamine and haloperidol in monkeys (cercopithecus aethiops) were investigated. Amphetamine increased locomotor activity and reactivity and induced repetitive movements of head, limbs and trunk, but no oral hyperkinesia. Haloperidol induced dystonia and parkinsonism. Pretreatment with the 5-HT antagonists cyproheptadine and mianserin increased amphetamine-induced locomotor activity, reactivity and repetitive movements and decreased haloperidol-induced dystonia and parkinsonism. Conversely the 5-HT uptake inhibitors paroxetine and CGP 6085 A decreased amphetamine-induced repetitive movements and aggravated haloperidol-induced dystonia and parkinsonism. The 5-HT uptake inhibitors produced oral hyperkinesia resembling human tardive dyskinesia, which was intensified by amphetamine and blocked by haloperidol. These findings support the suggestion that 5-HT inhibits dopamine functions and may imply that 5-HT antagonists could have a beneficial effect against acute extrapyramidal side-effects of neuroleptic treatment. 5-HT uptake inhibitors in the monkey may serve as a model for tardive dyskinesia.

Animals↗

Influence of native and randomized peanut oil on lipid metabolism and aortic sudanophilia in the vervet monkey.

Vervet monkeys (Cercopithecus aethiops pygerethrus) were fed cholesterol-free, semipurified diets containing 40% sucrose, 25% casein, 15% cellulose and 14% peanut oil (PNO), randomized peanut oil (RPNO) or corn oil (CO). After 4 months, serum cholesterol and triglyceride levels, serum lecithin-cholesterol acyl transferase (LCAT) activity and plasma lipoprotein lipase (LPL) activity were similar in all groups. Livers of monkeys fed CO converted 156% more acetate and 24% more mevalonate to cholesterol than those of monkeys fed RPNO. Cholesterogenesis in RPNO-fed monkeys was enhanced compared to PNO (68% from acetate; 62% from mevalonate). Incidence of atherosclerosis was 33% in monkeys fed RPNO, 80% in those fed CO and 90% in those fed PNO. Extent of sudanophilia was lowest in aortas of monkeys fed RPNO. Incidence of arteriosclerosis was 40% in monkeys fed CO, 56% in those fed RPNO and 70% in those fed PNO. Extent of aortic surface showing arteriosclerosis was highest in monkeys fed RPNO.

Animals↗

Effects of varying dietary fatty acid ratios on plasma lipids and platelet function in the African green monkey.

The influence of varying dietary fatty acid ratios on plasma lipids, platelet function and the potential for thrombosis was evaluated in the African green monkey (Cercopithecus aethiops), an animal model widely used in cardiovascular research. Ten adult animals, 5 males and 5 females, at intervals of 2 months, were fed a series of 7 diets with fatty acid ratios (P:S) ranging from 3:1 to 1:4. Platelet aggregation in vitro, plasma levels of beta-thromboglobulin and platelet factor 4, platelet membrane fatty acid composition and plasma lipids including total cholesterol, HDL and LDL were monitored at the end of each dietary period. Platelet hypersensitivity to ADP aggregation (3 and 10 microM) and plasma beta-thromboglobulin were elevated in both males and females when dietary P:S exceeded 1.5:1 (beta-TG = 45 ng/ml) as compared to control diets either reflecting current North American or that recommended as a desirable dietary goal (P:S = 1:1, beta-TG = 10 ng/ml). Diets enriched in saturated fatty acids (P:S = 1:2) also altered platelet function, but the effects were most consistently observed in female animals (beta-TG = 32 ng/ml). Platelet hypersensitivity was lost and beta-TG levels were at baseline when the animals were returned to the control diets. Platelet sensitivity did not correlate with membrane composition which generally reflected dietary composition. Both the saturated and the polyunsaturated fatty acid enriched diets lowered plasma HDL levels, and the saturated fatty acid diets elevated plasma LDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hepatitis in vervet monkeys caused by Fusarium moniliforme.

The fungus Fusarium moniliforme Sheldon is a common contaminant of maize (Zea mays L.) intended for human and animal consumption throughout the world. Culture material of F. moniliforme MRC 826, isolated from home-grown maize in an area in Transkei, southern Africa, with a high rate of human oesophageal cancer, was highly toxic to vervet monkeys (Cercopithecus pygerythrus). Ten monkeys were fed a standard primate diet which contained various amounts of culture material for 180 days. Two control monkeys received the standard diet without culture material. Pathological changes observed in liver biopsies taken by laparotomy were characterized by focal disturbance of the trabecular structure, degeneration and necrosis of hepatocytes, mononuclear infiltration, and in severe cases by cirrhosis. Biochemical changes, particularly increases in liver enzyme activities in serum, paralleled the liver damage seen by light microscopy. The acute, subacute and chronic toxic hepatitis induced in various degrees in all the monkeys fed fungal culture material showed close similarity with human viral hepatitis. The lesions also have some similarities to those induced in primates by aflatoxin, but differ in several respects. Ultrastructural nuclear and nucleolar changes caused by F. moniliforme, i.e. marginal clumping of chromatin and large nucleoli with segregation of fibrillar and granular components, suggested some similarity with the changes reported to be caused by aflatoxin and some other hepatocarcinogens. A long-term feeding experiment in vervet monkeys with F. moniliforme MRC 826 and attempts to isolate and chemically characterise the hepatotoxic metabolite(s) produced by this fungus are being continued.

Alanine Transaminase↗

Molybdate and the molecular properties of the vervet monkey estrogen receptor.

The Vervet monkey (Cercopithecus aethiops pygerythrus) uterine estrogen receptor was partially characterised. The effect of the molybdate oxyanion on various molecular properties of the receptor was investigated. Molybdate appeared to affect the subunit structure and apparent heterogeneity of the receptor. Anion exchange chromatography of uterine cytosols yielded two ligand binding subunits in a 1:1 ratio in the absence of sodium molybdate, while only a single labelled complex could be demonstrated in cytosols prepared in molybdate containing buffers. Chromatofocussing of the nonstabilized cytosols revealed substantial receptor heterogeneity (7 peaks) while a much simpler pattern (2 peaks) could be observed in the presence of the molybdate. Likewise, iso-electric focussing of labelled cytosols on agarose gels yielded at least 3 high affinity binding components (pI:6.8, 6.2, 5.9) in the absence and only one major band in the presence of sodium molybdate (pI 5.9).

Animals↗

Comparison of ketamine, physical restraint, halothane and pentobarbital: lack of influence on serotonergic measures in monkeys and rats.

The consequences of the use of ketamine for immobilization have been examined on the concentration of whole blood serotonin, concentrations of neurotransmitters and metabolites in CSF and brain, and specific binding of ligands related to neurotransmitters in brain. Vervet monkeys (Cercopithecus aethiops sabaeus) were examined under conditions which compared ketamine with physical restraint and with halothane. It was found that ketamine, used acutely in monkeys for restraint, had no influence on the concentration of serotonin in whole blood or the concentration of 5-hydroxyindoleacetic acid or homovanillic acid in the CSF. In rats, untreated animals were compared with those treated with ketamine alone, or in conjunction with pentobarbital. Treatment with ketamine had no influence on the specific binding of ketanserin, imipramine, prazosin or dihydroalprenolol in brain of rat, nor any influence on the concentrations of serotonin, 5-hydroxyindoleacetic acid, norepinephrine, epinephrine, dopamine, or dihydroxyphenylacetic acid in brain. A moderately increased concentration of homovanillic acid was observed in several areas of the brain of the rat after ketamine alone or paired with pentobarbital.

Animals↗

Laboratory vector studies on six mosquito and one tick species with chikungunya virus.

The tick Ornithodoros savignyi and the mosquitoes Culex horridus, Culex quinquefasciatus, Aedes fulgens, Ae. furcifer and Mansonia africana were tested for infection rates and ability to transmit chikungunya virus. O. savignyi and Cx quinquefasciatus did not become infected and Cx quinquefasciatus failed to transmit the virus between vervet monkeys, Cercopithecus aethiops. Only one of 17 Cx horridus feeding on a blood-virus mixture became infected which included infection of the salivary glands. Ae. fulgens had a high infection rate and transmitted the virus between Mystromys albicaudatus rodents. Ae. furcifer and Ma. africana both transmitted virus between vervet monkeys: the 50% infection threshold and the transmission rate were less than 4.5 logs and 25% respectively for Ae. furcifer and c. 5.5 logs and 29% for Ma. africana. In a further test, Ae. furcifer transmitted virus from a monkey to hamsters at a transmission rate of 32%. Attempts to demonstrate transovarial transmission of the virus in Ae. aegypti and Ae. furcifer were unsuccessful. It is concluded that Ae. furcifer is fitted for its suspected role as epidemic vector and that Ma. africana could also act as an important epidemic vector in southern Africa.

Animals↗

Distribution and excretion of a single dose of the mycotoxin fumonisin B1 in a non-human primate.

Fumonisin B1 (FB1), a toxic and carcinogenic secondary metabolite of the fungus Fusarium moniliforme Sheldon, was administered either by i.v. injection or by gavage to vervet monkeys (Cercopithecus aethiops). FB1 dosed by i.v. injection to two female vervet monkeys was rapidly eliminated from plasma with a mean half-life during the elimination phase of 40 min. Analysis of urine and faeces over a 5 day period after dosing gave an average 47% recovery of the dose as FB1 and its hydrolysed analogues. Two female vervet monkeys were given a single gavage dose of 14C-labelled FB1. During the subsequent 3 day period, faecal excretion of radioactivity accounted for an average of 61% of the administered dose and urinary excretion 1.2%. Residual radioactivity was recovered in low levels from skeletal muscle (1%), liver (0.4%), brain (0.2%), kidney, heart, plasma, red blood cells and bile (each 0.1%), while the contents of the intestines accounted for a further 12% of the radioactive dose. In total, 76% of the administered radioactivity was recovered. Analysis of the faeces, intestinal contents and urine indicated that over 90% of the radioactivity in these samples was due to FB1 and its hydrolysis products.

Administration, Oral↗

Disruption of sphingolipid metabolism in non-human primates consuming diets of fumonisin-containing Fusarium moniliforme culture material.

The fumonisin mycotoxins are produced by Fusarium moniliforme Sheldon, a contaminant of corn worldwide. The two most abundant analogues (fumonisins B1 and B2) are known to be potent inhibitors of sphingosine N-acyltransferase (ceramide synthase) and hence to disrupt de novo sphingolipid biosynthesis. The sphingoid bases, sphingosine and sphinganine (and hence their ratio), were measured at varying intervals over a period of 60 weeks in the serum of non-human primates (vervet monkeys; Cercopithecus aethiops) which were consuming diets containing 'low' and 'high' amounts of F. moniliforme culture material, such that their total daily fumonisin intake was approximately 0.3 and 0.8 mg/kg body weight/day, respectively. Although no significant differences were found in the serum levels of sphingosine compared to controls, serum sphinganine levels in the experimental groups (mean of 219 nM and 325 nM, respectively) were significantly (P = 0.02) elevated above the levels in controls (mean 46 nM). As a consequence, the ratio sphinganine:sphingosine was significantly (P = 0.003) elevated from a mean of 0.43 in the control group to 1.72 and 2.57 in the experimental groups, respectively. Similar changes in sphingolipid profiles were also measured in urine with an increase of the ratio from 0.87 in controls to 1.58 and 2.17 in the experimental groups, although the differences were not statistically significant. Hence, the disruption of sphingolipid biosynthesis in vervet monkeys by fumonisins in culture material added to their diet can effectively be monitored in the serum as an elevation of the sphinganine:sphingosine ratio.

Animals↗