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[Prevalence of Flavivirus antibodies in Alouatta caraya primate autochthonous of Argentina].

Flavivirus constitute a human health problem in our country. Primates are known to participate in the maintenance of Dengue and Yellow Fever viruses. However, these animals play a role which still remains to be determined in the maintenance of other viruses with potential pathogenicity for human beings and/or animals. Detección of antibodies was performed for different flavivirus in 105 sera samples of Alouatta caraya primates by the hemagglutination inhibition (HI) test. The neutralization (NT) test confirmed only infections caused by St. Louis Encephalitis (SLE) virus with a high prevalence in HI (35.23%) and NT (32.38%) antibodies. No antibody titres indicative of infections by Yellow Fever, Dengue and Bussuquara viruses were registered. Infection by the liheus virus could not be confirmed in these primates. There is a need for studies to detect new or reemergent viral infections in Argentina and the role that these primates could play in the maintenance of such infections.

Alouatta↗

Topographic patterns of v2 cortical connections in a prosimian primate (Galago garnetti).

Topographic patterns of cortical connections of the second visual area (V2) were examined in a lorisiform prosimian primate (Galago garnetti). Up to five different tracers were injected into dorsal and ventral V2. Tracers included wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) and up to four fluorochromes. Tracer injections consistently labeled neurons and terminals in primary visual cortex (V1), V2, the middle temporal area (MT), and the dorsolateral visual area (DL). Labeled neurons were also found in other proposed extrastriate areas such as the dorsomedial visual area (DM), dorsointermediate area (DI), middle temporal crescent (MTc), medial superior temporal area (MST), ventral posterior parietal area (VPP), and caudal inferotemporal cortex (ITc), but these connections were more variable and less dependent on the retinotopic position of injection sites in V2. Areal boundaries were identified by differences in cytochrome oxidase (CO) and myelin staining. We conclude that V2 cortical connections in prosimian galagos are similar to those in simian primates, suggesting that prosimians and other lines of primate evolution have retained several visual areas from a common ancestor that relate to V2 in similar ways. Architectural features of striate and extrastriate areas in prosimian galagos are similar to simian primates, with notable exceptions such as stripes in V2, which appear to be less differentiated in galagos.

Animals↗

Applications of microdialysis methodology in nonhuman primates: practice and rationale.

This review provides a comprehensive summary of the use of microdialysis procedures in nonhuman primates. Using these methods in primates is feasible, including both the anesthetized and awake preparations. The latter permit neurochemical sampling during complex information processing and behavioral performance. The close homology in structure and function between human and nonhuman primate brain makes using nonhuman primates particularly appealing, and the literature suggests that their use has provided instances of unique insight into brain structure and function. The continued use of these methods in areas such as the neurobiology of addiction, affective disorders, and psychosis will help in our ever-increasing understanding of the complex pathophysiologies of these disorders.

Animals↗

Standardized electroretinography in primates: a non-invasive preclinical tool for predicting ocular side effects in humans.

This paper reviews the use of a standard protocol for electroretinography in drug safety evaluation studies with non-human primates. The architecture and physiology of the eye of humans and higher primates are very similar, thus making the non-human primate a preferred animal model for evaluating potential ocular side effects of drugs in humans. Using the technical and procedural features of the human protocol, i.e., the standard for clinical electroretinography (SCE), electroretinography can be routinely performed from early- to late-phases of drug development as a toxicodynamic endpoint for retinal toxicity and potential neurotoxicity in non-human primates. Hence, scientists can collect clinically relevant data using a standardized testing procedure found in the SCE. This is important in drug safety evaluations since the SCE is an established protocol that lends itself easily for incorporation into studies requiring adherence to international Good Laboratory Practice regulations. The technique is non-invasive, painless, and confers no adverse effects or damage to the eye.

Animals↗

Summary of latent effects in long term survivors of whole body irradiations in primates.

The USAF School of Aerospace Medicine, Radiobiology Division, Brooks Air Force Base, Texas presently is maintaining a colony of over 450 primates in which the whole body has been exposed to various types of space radiation including protons and electrons. The majority of the primates (Macaca mulatta) were exposed during 1965. Types of radiation involved are 2 MeV X-rays, 5 MeV-2.3 GeV protons and 1.6 MeV electrons. Low energy proton dose range up to 3000 rad (50-100 rad min-1) whereas the penetrating energy doses range up to 700 rad (15-100 rad min-1). Primates from a simulated solar flare exposure are also included. In late 1970, a small group of primates exposed to 108 and 85 MeV alpha particles (eye and partial body only) were added to the colony. Data are available in the following areas: (i) chronic skin changes; (ii) testicular atrophy; (iii) cataractogenesis; (iv) hematological and serum biochemical analysis; (v) incidence of tumors; (vi) causes of death; (vii) body weight variations; and (viii) summary of alpha particle experiences.

Alpha Particles↗

[Molecular mechanisms for the development and aging of the primate central nervous system].

The central nervous system (CNS) of primates, including humans, is more complex than the CNS of other mammals. In particular, the cerebral cortex expands during evolution and this has resulted in the emergence of higher cognitive abilities in primates. Recent neurochemical and neuroanatomical methods have clarified the presence of various neuroactive substances including neuropeptides, neurotrophic factors and growth associated proteins in the developing mammalian cerebral cortex. Among these signal molecules, we have focused on somatostatin (SRIF), neurotrophins (BDNF, NT-4/5 and NT-3) and their receptors (Trk), growth associated proteins such as GAP-43 and SCG-10 during the development and aging of primate CNS. We found that although full-length TrkB, a high affinity receptor for BDNF and NT4/5, was detected from the embryonic stage to adulthood, the level of truncated TrkB which lacks tyrosine kinase domain, only increased after birth. This development of truncated TrkB correlated well with down-regulation in the gene expression of GAP-43 and SCG-10. The reductions of GAP-43 and SCG-10 may result in the elimination of callosal axons in the monkey cerebral cortex after birth. The highest levels of BDNF protein in the various cerebral cortices occurred between postnatal 1 and 6 when the number of synapses is highest. In contrast, there was no transient increase in the levels of NT4/5 or NT3 after birth. These findings suggest that BDNF is one of the candidates for the synaptic development of the primate cerebral cortex. During aging processes, we observed decreases in the levels of SRIF and BDNF mRNAs in the cerebral cortex. Since BDNF is an upstream gene expression molecule of SRIF, the decline of SRIF mRNA during aging may be due to the decrease in the gene expression of BDNF. Similar reductions of gene expressions of SRIF and BDNF in the brains of the patients with Alzheimer's disease, suggest that aged monkeys are good model animals for these neuro-degenerative diseases.

Aging↗

Prevalence of cryptosporidium and other enteric parasites among wild non-human primates in Polonnaruwa, Sri Lanka.

Cryptosporidiosis is a rapidly emerging disease in the tropics. This is the first report of Cryptosporidium and other protozoan infections (Entamoeba spp., Iodamoeba, Chilomastix, and Balantidium spp.) in wild primates that inhabit the natural forest of Sri Lanka. It is unclear if non-human primates serve as a reservoir for these parasites under certain conditions. A cross-sectional coprologic survey among 125 monkeys (89 toque macaques, 21 gray langurs, and 15 purple-faced langurs) indicated that Cryptosporidium was detected in all three primate species and was most common among monkeys using areas and water that had been heavily soiled by human feces and livestock. Most macaques (96%) shedding Cryptosporidium oocysts were co-infected with other protozoans and important anthropozoonotic gastrointestinal parasites (e.g., Enterobius and Strongyloides). The transmission of these parasites among primates in the wild may have important implications for public health as well as wildlife conservation management.

Animals↗

Genetic diversity at class II DRB loci of the primate MHC.

The evolution of polymorphism at loci encoding the beta-chains of the MHC class II DR Ag was studied in primates by DNA amplification (polymerase chain reaction). Phylogenetic analysis of 63 DRB sequences from the polymorphic second exon (first domain) of nonhuman primates and 53 human sequences indicates the presence of five DRB loci in primates, derived from a DRB1-like ancestral locus over 20 million yr ago. Many of the allelic types at the DRB1 locus predate the divergence of hominoids (5 million yr ago) and some (DR4, DR3, 5, 6) predate the divergence of Old world monkeys and hominoids (20 million yr ago). The DRB3 locus appears to have arisen before the divergence of hominoids on an ancestral DRB1 lineage. The DRB2 and DRB5 loci were generated more than 20 million yr ago and the DRB4 locus more than 5 million yr ago. The DRB2 locus, a pseudogene in humans, is polymorphic in the nonhuman primates.

Amino Acid Sequence↗

[Primates in the study of hepatitis viruses].

There is no a conventional tissue culture system for the propagation of the hepatitis viruses and only some of them can be maintain in continuous cell culture in particular conditions. A transmissibility of hepatitis is limited to primates. The narrow host specificity may help to establish the classification of the hepatitis viruses and their mode of transmission. Moreover, the primate animal model provided the most accessible source of viruses and for clinical reasons presents the only opportunity for the studies of pathogenic mechanisms involving cellular immunity with allogenic restriction. The marmosets and chimpanzees susceptible to the hepatitis A and B viruses, respectively are the primates of choice for the experimental models. For the studies on parenterally transmitted NANB hepatitis the chimpanzee and some rhesus monkeys may provide an animal system. At last, most of the primates seem to be susceptible to agent responsible for the water-borne non A non B hepatitis.

Animals↗

A social tethering system for nonhuman primates used in laboratory research.

A housing and tether system was designed to permit sampling of body fluids, chronic monitoring of physiologic parameters (e.g. blood pressure, heart rate), performance of species typical behavioral interactions (aggression, affiliation, reproduction, etc), physical exercise (work on a motorized treadmill), assessment of water and diet consumption, as well as feces and urine collection. The system provided primates with the opportunity to engage in species typical social behavior and thereby minimized conditions which have been identified as contributing to the development of abnormal behaviors associated with individual housing. The system consisted of two parts: (a) a specialized cage system for housing small social groups of primates and (b) a tether and indwelling catheter system. Each modular system permitted four adult baboons (Papio cynocephalus anubis) to be tethered and housed in a social group. Each cage was 2.44 x 2.44 x 1.22 m (L x W x H) and could be subdivided by means of woven wire wall partitions. The tether system consisted of a backpack, a cloth jacket, a stainless-steel flexible cable containing electrical cables and catheters, and a saline infusion pump mounted on top of the cage. The system provides laboratory primates with the ability to socially interact with other nonhuman primates. The social cage tether system represents an example of a housing environment which could conform to both the letter and spirit of the new animal welfare legislation and still remain compatible with the objective of obtaining scientific data.

Animal Welfare↗

Calorie-nitrogen interactions in the parenterally fed primate.

To test the hypothesis that nonprotein calorie intake and nitrogen intake are equally important in establishing positive nitrogen balance, weight gain, and serum protein response in the depleted primate treated with total parenteral nutrition (TPN), 10 adult male chair-adapted primates (Macaque fascicularis) were studied. After 10 days of nutritional depletion (nothing by mouth; 5% dextrose with electrolytes administered intravenously) animals were randomized to receive one of four TPN diets for 10 days. The depletion/repletion cycle was repeated, after 1 month of caged free feeding, until all animals had received the four TPN diets. Two levels of nonprotein caloric intake (155% and 100% of primate resting energy expenditure) and two levels of nitrogen intake (200% and 100% of primate nitrogen requirement) were used to make the four different diets. Nitrogen balance (p = 0.01) and serum total iron-binding capacity response (p = 0.02) were significantly influenced by the level of nitrogen intake but not by nonprotein calorie intake, which significantly influenced only weight gain (p = 0.03). Fluid balance was not significantly different for any diet. Fat and protein stores may be selectively repleted in this model by adjusting the nonprotein calorie and nitrogen content of TPN.

Animals↗

Plasma and hepatic apoE isoproteins of nonhuman primates. Differences in apoE among humans, apes, and New and Old World monkeys.

We have used two-dimensional polyacrylamide gel electrophoresis (PAGE) to study the plasma and hepatic apoE isoproteins of nonhuman primates and have compared them with their human counterparts. We have found that apoE obtained from fresh monkey or ape plasma, as well as nascent apoE synthesized by perfused monkey livers, is composed of several isoproteins that resemble the homozygous (beta) apoE phenotype observed in humans. The nonhuman primate plasma apoE pattern of 90 animals from nine different species consisted of a major isoprotein designated apoE3 and a few minor isoproteins. A group of acidic apoE isoproteins is eliminated after treatment with C. perfringens neuraminidase and has been designated sialo apoE (apoEs). Nonhuman primate liver apoE isoproteins comigrate with their plasma apoE isoprotein counterparts on two-dimensional PAGE, but hepatic apoE is enriched in sialo apoE isoproteins when compared to plasma apoE. The apparent molecular weight of asialo and sialo apoE obtained from Old World monkeys and apes is identical to the molecular weight of the corresponding human isoproteins (E3 = 38K, Es = 38.5-39.5K). However, the apparent molecular weight of apoE isoproteins obtained from New World monkeys is increased by approximately 0.5K (E3 = 38.5K, Es = 39.0-40.0K) as compared to the molecular weight of human and Old World monkey and ape isoproteins. The isoelectric points of apoE3 obtained from Old World monkeys, New World monkeys, chimpanzees, and gibbons are 5.74, 5.76, 5.95, and 5.89, respectively. The entire New or Old World monkey, chimpanzee, and gibbon apoE pattern is shifted by approximately -2.0, -0.5, and -1.0 charges, respectively, relative to the pattern of the corresponding human E3/3 phenotype. The molecular weight difference in apoE observed among New and Old World monkeys, as well as the molecular weight and/or charge differences observed among monkey, ape, and human apoE are consistent with structural changes in the apoE gene which have occurred following the divergence of the different species. The observation of only the homozygous apoE phenotypes in all animals studied suggests that the common apoE genetic polymorphism recently described in humans may not be present in nonhuman primates.

Animals↗

Evolution of glycophorin A in the hominoid primates studied with monoclonal antibodies, and description of a sialoglycoprotein analogous to human glycophorin B in chimpanzee.

Comparison of human and primate erythrocyte membrane sialoglycoproteins showed that common chimpanzee, dwarf chimpanzee, gorilla, orangutan, and gibbon have major periodic acid Schiff-positive proteins resembling human glycophorin A (GPA) monomer and dimer in electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels. Immunoperoxidase staining of Western blots with monoclonal antibodies to human GPA showed that these primate bands express some GPA antigenic determinants. A new sialoglycoprotein analogous to human glycophorin B (GPB) was detected in common chimpanzee. Although human MN blood group phenotype results from an amino acid polymorphism of GPA, Western blots showed that in chimpanzee sialoglycoprotein (GPAch) always expresses the M blood group, whereas chimpanzee sialoglycoprotein (GPBch) expresses either the N blood group or a null phenotype. This result explains the detection of M and MN, but not of N, blood group phenotypes in chimpanzee. GPBch has higher apparent m.w. than human GPB, is present in the erythrocyte membrane in greater quantity than human GPB, and contains trypsin cleavage site(s) and the 10F7 determinant (both found on human GPA but not GPB). Expression of human GPA antigenic determinants was consistent with the phylogeny of the hominoid primates; common and dwarf chimpanzee expressed most of the determinants tested, gorilla and orangutan an intermediate number, and gibbon and siamang the least. Of the GPA antigenic determinants examined, the MN blood group determinants were most consistently expressed during evolution of the hominoid primates. The results suggested that variability in expression of GPA antigenic determinants between species was due to both differences in amino acid sequence and glycosylation.

Adult↗

Nonhuman primates express human leukemia-associated antigens.

Serologic studies using four murine monoclonal antibodies specific for the common acute lymphoblastic leukemia antigen (CALLA) and five monoclonal antibodies specific for the gp24 surface antigen indicate that these leukemia-associated antigens are present on cells of comparable tissues in man and in four nonhuman primates. As in man, adherent cell populations obtained from skin, lung, and bone marrow of Macaca fascicularis, M mulatta, M nemestrina, and Papio cynocephalus react with these antibodies. Similarly, granulocytes from both man and these nonhuman primates bind CALLA- and gp24-specific antibodies. Radioimmune precipitation experiments confirm the identity of these antigens. Our studies suggest that nonhuman primates can be used to screen serologic reagents to leukemia-associated antigens for potential toxic effects on normal tissues prior to their use in man. Similarly, nonhuman primates could be employed to assess the possible role of antigen-positive stromal cells in the reconstitution of bone marrow following transplantation.

Animals↗

Change in short-latency response to limb displacement in primates.

When a muscle is stretched in an awake, behaving primate the earliest electromyographic (EMG) responses of the muscle consists of several reflex components. The earliest, M1, is mediated entirely at the segmental level and is largely monosynaptic. The next M2, is at least in part the result of an oligosynaptic transcortical loop to control the M1 response remains to be established. If primates can learn to control M1 amplitude, the M1 loop, which is the simplest and most accessible stimulus-response pathway in the primate central nervous system, may serve as a model for the study of mechanisms of memory. Preliminary evidence presented here strongly suggests that primates can control M1 gain without change in prestimulus EMG activity. The mechanisms of such change remain to be determined. Possibilities include change in gamma motor neuron tone, in Ia synaptic function, and in alpha motor neuron recruitment. The usefulness of learned M1 change as a model for memory will depend to a large extent on the nature of the responsible mechanism and on demonstration that the change can eventually become resident at the segmental level, without need for continued descending input.

Animals↗

The effects of an immunomodulatory LFA3-IgG1 fusion protein on nonhuman primates.

LFA3TIP, a fusion protein comprised of the first extracellular domain of LFA-3 fused to the hinge, CH2 and CH3 domains of human IgG1, inhibits proliferation of human T cells in vitro. LFA3TIP also inhibits responses of human CD2 transgenic mice by rapidly and totally depleting peripheral T cells. These effects require binding of the LFA-3 and CH2 domains of LFA3TIP to CD2+ T cells and Fc gamma R+ accessory cells, respectively. As CD2 is well conserved in primate species, we evaluated the effects of LFA3TIP in nonhuman primates. We report in vitro results leading to the selection of the baboon as a model for analysis of LFA3TIP, and in vivo effects of single and multidose regimens of LFA3TIP administration. This is the first report of the in vivo administration of an immunomodulatory fusion protein to primates. LFA3TIP is shown to mediate effects on primate T lymphocytes without apparent related toxicities or immunogenicity. Results are discussed in context of potential mechanisms of LFA3TIP immunotherapy.

Adjuvants, Immunologic↗

Type D primate retroviruses: a review.

The prototype virus of the type D retroviruses is the Mason-Pfizer monkey virus (MPMV). MPMV was originally isolated from a breast carcinoma of a female rhesus monkey (an Old World monkey). MPMV is of obvious importance in that it is the only retrovirus thus far isolated from a mammary tumor of a primate and has been shown to have transforming potential for primate cells in vitro. Subsequent to the isolation of MPMV viruses morphologically and immunologically indistinguishable from MPMV have been isolated from normal placenta and lactating mammary glands of other rhesus monkeys in captivity. Recently, viruses morphologically resembling MPMV have been isolated from a langur monkey (another Old World monkey) and from squirrel monkeys (a New World monkey). Based on nucleic acid hybridization studies, the latter 2 viruses represent endogenous viruses in their species of origin, whereas MPMV appears to be a horizontally related to the langur monkey isolate. Studies on the immunological relatedness of the type D retroviruses have demonstrated interspecies cross-reactivities between the major internal and external proteins of the viruses. Furthermore, these viruses also share cross-reactivity of their major external glycoproteins with those of the type C baboon endogenous virus. These interspecies reactivities can also be demonstrated in natural sera from both imported and laboratory-bred monkeys. The demonstration of these interspecies cross-reactivities shared by distantly related primate retroviruses provides a means for detecting determinants that are representative of all primate retroviruses presently known and yet to be isolated and may provide new assays for detection of a human retrovirus.

Animals↗

Tactile discrimination capacity in relation to size and organization of somatic sensory cortex in primates: I. Old-World prosimian, Galago; II. New-World anthropoids, Saimiri and Cebus.

Living primates vary considerably in brain organization, in sensorimotor and cognitive abilities, and in natural behavioral repertoires. Comparative studies of primary (SI) and secondary (SII) somatic sensory cortex of primates reveal major differences in the size and in the complexity of topographic projection patterns. The separate projections of the glabrous hand to SI cytoarchitectonic areas 3b and 1 described in the Old World (OW) anthropoid Macaca and in New World (NW) anthropoids Cebus, Saimiri, and Aotus are lacking in NW Saguinus and in the prosimian Galago. The relationship between the size and complexity of SI organization and tactile abilities is explored in this study of four species of primates--Galago, Macaca, Cebus, and Saimiri. These species were trained to discriminate between pairs of objects differing either in cross-sectional diameter (size) or surface roughness (texture). The course of acquisition of such tactile discrimination in normal Macaca and the nature of deficits following SI or SII removals are known. Selective lesions of either cytoarchitectonic area 1 or 2 in Macaca affect only texture or size discriminations, respectively. Removal of area 3b in SI, or of SII, in Macaca affects both size and texture capacities. The single projection of the glabrous hand to area 3b-1 of Galago led to our expectation that the capacity of Galago to discriminate textures would be more similar to an area 1-lesioned than to a normal Macaca. The substantial and persistent differences between Macaca and Galago on texture, but not size, tasks lend support to the view that the evolution of a second projection of the glabrous hand to area 1 in Macaca contributes to increased texture discrimination capacity. The similarity in multiple projection patterns of the glabrous hand to areas 3b and 1 in Macaca, Saimiri, and Cebus led us to expect greater correspondence in texture discrimination capacity between these three anthropoids than to Galago. Contrary to expectations, Saimiri and Cebus showed a tactile capacity more similar to Galago than to Macaca. Furthermore, the texture discrimination capacity of Cebus actually improved substantially after removal of area 1. This provides further evidence, together with the single SI hand area in NW Saguinus and Galago, that the separate cutaneous projections to area 1 in OW and NW primates are not homologous but evolved independently and possibly serve different tactile functions.

Animals↗