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Identification of a competitive binding component in vitamin D-resistant New World primate cells with a low affinity but high capacity for 1,25-dihydroxyvitamin D3.

Monkeys in a number of different New World primate genera express a form of compensated target organ resistance to steroid hormones, including 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Characterization of these phenotypes has previously relied upon the study of the 1,25-(OH)2D3-receptor (VDR) interaction in cultured dermal fibroblasts from affected primates. In this report, we show that three of these prototypic phenotypes can be faithfully reproduced in previously established cultured cell lines: B95-8, EBV-transformed B lymphoblasts from the marmoset (Callithrix jacchus), a New World primate with recognized vitamin D resistance; OMK, renal tubular epithelial cells from the owl monkey (Aotus trivergatus), a New World primate with an Old World primate-like VDR phenotype; and MLA144, transformed B lymphoblasts from a gibbon (Hylobates), an Old World primate that expresses the wild-type VDR phenotype. The rank order of specific nuclear uptake and binding of [3H]1,25-(OH)2D3 to the VDR was OMK > or = MLA144 >> B95-8. Despite a 7- to 9-fold difference in cellular VDR content according to ligand binding analyses, there was no discernible difference in the internalization constant Kin for specific cellular uptake of [3H]1,25-(OH)2D3 (0.12-0.26 nM) or in the quantity of VDR detected by immunoblot analysis. We now speculate that the discrepancy in VDR quantitation by binding and immunoblot analysis in the B95-8 New World primate cell line results from the presence of an intracellular, vitamin D metabolite binding moiety in this cell line that competes with the VDR for metabolite binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The interrelationship of lens anatomy and optical quality. II. Primate lenses.

We have quantified the influence of lens sutural anatomy on optical quality (focal length variability, i.e. spherical aberration) in adult monkeys (Macaque nemestrina). Adult lenses (n = 6) were initially scanned by a low-power helium-neon laser beam that was passed at a series of acute angles to, and/or directly through, lens sutures. Optical analysis showed that while the 'star' sutures of primate lenses exerted a quantifiable negative effect on focal length variability, this detrimental effect was far less significant than that attributable to 'line' and 'Y' sutures in non-primate lenses. Correlative morphological and 3-D computer-assisted drawing (CAD) analysis of the laser-scanned lenses areas, as well as of variably aged lenses (n = 30), revealed that primates have a more complex lens architecture than non-primates. Non-primate lenses feature suture planes, aligned along the visual axis that are responsible for a significant quantifiable increase in spherical aberration. Primate lenses are characterized by an absence of continuous suture planes aligned along the visual axis. Rather, 3-D-CADs of primate lenses demonstrate that distinct generations of progressively more complex sutures are produced as a function of development, growth, and age. In succession, 'Y' sutures (three branches) are formed throughout embryonic development, 'simple star' sutures (three-six branches) evolve after birth and through infancy, 'star' sutures (six-nine branches) are made in young adult lenses and, finally, 'complex star' sutures (nine-15 branches) are laid down from middle through old age. In view of the fact that slit-lamp evaluation of cataractous lenses often reveals abnormally thin zones of discontinuity, it is significant to note that the temporal development of the zones of discontinuity in normal human lenses is essentially identical to the progressive iteration of offset monkey lens sutures. In conclusion, these studies describe a specific structural aspect of lenses that adversely influences optical quality, and relates it to the most commonly employed clinical technique to identify and monitor the progress of cataracts.

Aging↗

Neurogenesis in the subventricular zone and rostral migratory stream of the neonatal and adult primate forebrain.

Throughout life, the anterior part of the postnatal rodent subventricular zone (SVZa), surrounding the lateral ventricles, contains a prolific source of neuronal progenitor cells that retain their capacity to concurrently generate neurons and migrate along the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into interneurons. This study was designed to determine whether the SVZ and RMS of the postnatal primate also harbor a specialized population of neuronal progenitors with the capacity to divide while they migrate. In order to reveal the spatial-temporal changes in the distribution and composition of the neuronal progenitor cells in the primate SVZ and RMS, seven rhesus monkeys, ranging in age from 2 days to 8 years, were given a single injection of the cell proliferation marker bromodeoxyuridine (BrdU) 3 h before they were perfused. The phenotypic identity of the BrdU(+) cells was revealed by double labeling sagittal sections with cell type-specific markers. From birth onward the distribution of BrdU(+) cells with a neuronal phenotype is extensive and largely overlapping with that of the rodent. Similar to the rodent brain the neuronal progenitors are most numerous in neonates. The BrdU(+) neurons in the primate forebrain extend lateral and ventral to the lateral ventricle and all along the RMS. The cytoarchitectonic arrangement and appearance of the neuronal progenitor cells is quite varied in the primate compared to the rodent; in some locations the cells are aligned in parallel arrays resembling the neuronal chains of the adult rodent RMS, whereas in other positions the cells have a homogeneous "honeycomb" arrangement. The chains are progressively more pervasive in older primates. Akin to the RMS of adult rodents, in the primate SVZ and RMS the astrocytes often form long tubes enveloping the chains of neuronal progenitors. Our study demonstrates that the primate forebrain, similar to the rodent forebrain, harbors a specialized population of mitotically active neuronal progenitor cells that undergo extensive rearrangements while continuing to proliferate throughout life.

Aging↗

Overexpression of the FK506-binding immunophilin FKBP51 is the common cause of glucocorticoid resistance in three New World primates.

Many New World primates have high circulating levels of cortisol to compensate for the expression of glucocorticoid receptors (GRs) with low activity. Recent work in squirrel monkeys has suggested that this may be due to either the expression of GRs that are transcriptionally incompetent or the expression of an FK506-binding immunophilin that inhibits GR binding. The goal of this study was to resolve this controversy by determining the molecular basis of glucocorticoid resistance not only in species of squirrel monkeys but also in other glucocorticoid-resistant New World primates. First, the transcriptional activity of the GR from the Bolivian squirrel monkey was compared to that of the human GR. Incubation of COS-7 cells transfected with the squirrel monkey GR with 10 nM dexamethasone resulted in a robust stimulation of MMTV-luciferase activity (up to 260-fold), which was similar in magnitude to that achieved with the human GR. Second, the effect of FK506 on GR binding was determined in cytosol from cells from two species of squirrel monkeys as well as glucocorticoid-resistant cotton-top tamarins and owl monkeys. Incubation with 10 microM FK506 increased GR binding by at least 4-fold in cytosol from cells of each of the New World primates but had no effect on GR binding in cytosol from human WI-38 VA13 cells. Third, Western blots showed elevated expression of FKBP51 in New World primate cells and liver samples from two squirrel monkey species. On the other hand, the levels of FKBP52 were significantly lower in cells and liver from New World primates. The sequences of FKBP51 from the cotton-top tamarin, owl monkey and squirrel monkey are closely related and share differences from the human, rhesus monkey, mouse, and lemur FKBP51 sequences in the same 18 positions. Fourth, the relative activities of FKBP51 from the cotton-top tamarin, owl monkey and squirrel monkey were determined in cytosol mixing and GR transactivation studies and showed that FKBP51 from each of these primates was a potent inhibitor of GR activity. These results indicate that the elevated expression of FKBP51 contributes to glucocorticoid resistance in three New World primate genera.

Amino Acid Sequence↗

"Rodent-like" and "primate-like" types of astroglial architecture in the adult cerebral cortex of mammals: a comparative study.

Previous observations disclosed that astroglia with interlaminar processes were present in the cerebral cortex of adult New and Old World monkeys, but not in the rat, and scarcely in the prosimian Microcebus murinus. The present report is a more systematic and comprehensive comparative analysis of the occurrence of such processes in the cerebral cortex of several mammalian species. Brain samples were obtained from adult individuals from the following orders: Carnivora (canine), Rodentia (rat and mouse), Marsupialia (Macropus eugenii), Artiodactyl (bovine and ovine), Scandentia (Tupaia glis), Chiroptera (Cynopteris horsfieldii and C. brachyotis), and Primate: Prosimian (Eulemur fulvus), non-human primate species (Cebus apella, Saimiri boliviensis, Callithrix, Macaca mulatta, Papio hamadryas, Macaca fascicularis, Cercopithecus campbelli and C. ascanius) and from a human autopsy. Tissues were processed for immunocytochemistry using several antibodies directed against glial fibrillary acidic protein (GFAP), with or without additional procedures aimed at the retrieval of antigens and enhancement of their immunocytochemical expression. The cerebral cortex of non-primate species had an almost exclusive layout of stellate astrocytes, with only the occasional presence of long GFAP-IR processes in the dog that barely crossed the extent of lamina I, which in this species had comparatively increased thickness. Species of Insectivora and Chiroptera showed presence of astrocytes with long processes limited to the ventral basal cortex. Interlaminar GFAP-IR processes were absent in Eulemur fulvus, at variance with their limited presence and large within- and inter-individual variability as reported previously in Microcebus murinus. In New World monkeys such processes were absent in Callithrix samples, at variance with Cebus apella and Saimirí boliviensis. Overall, the expression of GFAP-IR interlaminar processes followed a progressive pattern: bulk of non-primate species (lack of interlaminar processes)--Chiroptera and Insectivora (processes restricted to allocortex) < strepsirhini < haplorhini (platirrhini < catarrhini). This trend is suggestive of the emergence of new evolutionary traits in the organization of the cerebral cortex, namely, the emergence of GFAP-IR long, interlaminar processes in the primate brain. Interlaminar processes may participate in a spatially restricted astroglial role, as compared to the one provided by the astroglial syncytium. It is proposed that the widely accepted concept of an exclusively astroglial syncytium is probably linked with a specific laboratory animal species ("rodent-type" or, rather, "general mammalian-type" model) that misrepresents the astroglial architecture present in the cerebral cortex of most anthropoid adult primates ("primate-type" model), including man.

Aged↗

Definition of the T-lymphocyte inducer of suppression in primates using a monoclonal antibody.

Since some of the conserved antigens between man and phylogenetically lower primate species may be more immunodominant on lymphocytes of the lower primate species, we reasoned that immunization of mice with lymphocytes from lower primates might prove a useful strategy for developing monoclonal antibodies which recognize functionally important structures on both human and nonhuman primate lymphocytes. In employing this approach for the development of monoclonal antibodies, we have developed the antibody anti-2H4 which recognizes a structure on both T on non-T mononuclear cells of a wide array of primate species. 2H4+ rhesus monkey T lymphocytes exhibited a greater proliferative response to lectin and alloantigenic stimulation than 2H4- cells, suggesting that anti-2H4 might separate primate T lymphocytes into functionally distinct cell populations. In fact, helper activity for antibody production by rhesus monkey B lymphocytes in response to pokeweed mitogen (PWM) resided in the 2H4- T-cell population. Furthermore, the 2H4+ T-lymphocyte population activated the suppressor function of T8+ rhesus monkey cells. The fact that the surface antigen which defines this T-cell subset is widely conserved in nonhuman primates suggests that anti-2H4 recognizes a functionally important structure.

Animals↗

MAC-1, a new genetically transmitted type C virus of primates: "low frequency" activation from stumptail monkey cell cultures.

A new class of endogenous primate type C virus has been isolated from a continuous tissue culture line of Macaca arctoides cells by co-cultivation with a human cell line. The virus, designated MAC-1, can be transmitted to human and feline cells in tissue culture, and is unrelated, by immunological and nucleic acid hybridization criteria, to previously characterized retroviral isolates of primates. In particular, MAC-1 shows no detectable homology to the baboon type C viruses, even though viral genes related to the latter group are readily detected in M. arctoides cellular DNA. Viral gene sequences related to the MAC-1 genome are present in multiple copies (50-150 per haploid genome) in Old World primates, and are expressed in the cellular RNAs of uninfected and "virus-free" primate cells and tissues. Thus there are at least two distinct sets of genetically transmitted Old World primate type C viral genes, each of which is found in multiple copies in normal primate cellular DNA. With the description of this new retrovirus, there are now a minimum of five distinct genetically transmitted viruses of primates, three type C and type D, each represented in multiple copies in the normal cellular DNA.

Animals↗

Screening for antiproliferative actions of mifepristone. Differential endometrial responses of primates versus rats.

This laboratory has previously shown the capability of the antiprogestin, mifepristone, to noncompetitively inhibit estrogen-induced endometrial proliferation in nonhuman primates. In the following study, use of the rat uterine weight bioassay was compared against a primate (Macaca fascicularis) uterine bioassay to identify the noncompetitive/antiproliferative effects of mifepristone. These uterine bioassays were contrasted for reasons of identifying a comparative laboratory rodent model that could substitute for the need to use primate models in the screening of potential antiprogestins, thereby saving time, cost, and primate resources. Results of the primate experiment showed that mifepristone decreased endometrial proliferation in a dose-dependent manner; importantly, this decrease occurred in the presence of sustained physiologic serum 17 beta-estradiol (E2) levels. However, in the rat model, results showed that mifepristone altered uterine wet weight and blotted weight values only in those animals receiving pharmacological doses of E2 (p < 0.05). Based on the results summarized herein, use of this rat uterine weight bioassay as a substitute for primate models is not recommended for screening and identification of "interesting" antiprogestins. Apparently, the endometrial noncompetitive antiestrogenic/antiproliferative effects of mifepristone, observed repeatedly in these laboratory primates, do not operate in the rat uterine tissue.

Animals↗

Origin and evolution of Asian hominoid primates. Paleontological data versus molecular data.

The origin and evolution of hominoid primates (apes and man) has long been studied exclusively on the basis of available fossil remains. Indeed, a migration of African primates towards Asia at about -16 to -17 Ma might have given the lineage of Miocene Asian hominoids. This hypothesis is supported by the oldest remains of Miocene Asian hominoids dated at about -16.1 Ma. But the recent discovery of anthropoid primates in the Eocene of Asia seems to indicate that Asia was a major evolutionary and differentiation centre for anthropoid primates as early as the Eocene. In addition, Asian primates probably continued to evolve in Asia from the Eocene onward and led at least to the extant Asian hominoids (orangutans and gibbons). African and Asian extant anthropoid primates might therefore have diverged at least 36 Ma ago, and this hypothesis is also supported by the most recent data in molecular biology. Moreover, an Asiatic origin of African Paleogene propliopithecine primates is suggested. In that context, evolutionary rates might not be constant, and molecular clocks should be necessarily characteristic for each studied group of mammals. Several examples that illustrate the conflict between paleontological and molecular data are discussed. The necessity to integrate more systematically paleontological data as chronological reference points in studies in molecular phylogeny is discussed.

Animals↗

Comparative study of target antigens for primate xenoreactive natural antibodies in pig and rat endothelial cells.

BACKGROUND: A rat-to-primate cardiac xenograft model has been proposed as an alternative to the clinically relevant but more cumbersome pig-to-primate model for assessing the efficacy of strategies aimed at preventing xenograft hyperacute rejection. As in pig xenografts, the rejection of rat hearts was mediated by the binding of xenoreactive natural antibodies (XNA) and complement activation. The present study was conducted to identify target antigens recognized by cynomolgus and rhesus monkey IgM XNA on rat tissues and cells in comparison with pig cells. METHODS: The reactivity of rhesus or cynomolgus serum on pig and rat endothelial cells (ECs) was studied by flow cytometry, ELISA, and complement-dependent cytotoxicity, after removal of primate XNA by perfusion of pig livers, immunoadsorption on a Gal alpha(1,3)Gal affinity column, and enzymatic removal of alpha-galactosyl epitopes from the cell surface. Rat and pig EC extracts were also immunoprecipitated with primate serum and resolved in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The expression of the Gal alpha(1,3)Gal epitope was analyzed on rat tissues and ECs by immunohistochemistry, flow cytometry, and Western blot, using the isolectin B4 from Griffonia simplicifolia. RESULTS: Removal of primate XNA or of alphaGal epitopes resulted in a decrease in XNA binding to pig and rat cells, leaving a similar degree of residual reactivity in the two species. At least five proteins of 260, 210, 110, 56, and 50 kDa were immunoprecipitated on rat ECs, with molecular weight similar to several proteins identified on pig ECs. These results suggest that primate XNA recognize similar antigens on rat and pig ECs. Rat cells expressed lower levels of the Gal alpha(1,3)Gal epitope than pig cells. A large proportion, but not all, of primate XNA react with this epitope on pig and rat ECs. CONCLUSION: This study suggests that the rat is a valuable species for the evaluation of genetic engineering strategies on the vascular endothelium aimed at preventing hyperacute xenograft rejection.

Animals↗

Endogenous blockade of 1,25-dihydroxyvitamin D-receptor binding in New World primate cells.

When assessed by 1,25-dihydroxyvitamin D3 (1,25(OH)2-D3)-receptor (VDR) binding analysis or 1,25(OH)2-D3-VDR-directed bioresponsiveness, cultured cells from some New World primates (platyrrhines) demonstrate a variable decrement in VDR when compared with Old World primate (catarrhine) cells. To study this difference in VDR expression among primates, we performed immunoblot analysis of the VDR in cultured dermal fibroblasts from platyrrhines in the genera Pithecia and Aotus and from catarrhines in the genus Presbytis; although a platyrrhine, the owl monkey (Aotus) expresses a VDR of the catarrhine (wild type) phenotype. Despite a 10-fold difference in the content of VDR by ligand binding analysis among cells from the three prototypic primate genera, there was a less than or equal to 10% difference in the steady-state level of 50-kD VDR detected by immunoblot analysis of cellular extracts. We investigated this apparent discrepancy in the content of VDR in immunoblots and ligand binding analyses by mixing VDR-containing nuclear extracts of equivalent protein concentration from the various primates. Coincubation of Pithecia and Aotus fibroblast extracts with Presbytis extract diminished specific 1,25(OH)2-D3 binding in the mix by 90% and 95% respectively. Similar results were obtained by mixing nuclear extracts of the owl monkey cell line, OMK, and the vitamin D resistant marmoset B-lymphoblast cell line B95-8. A wild type 1,25(OH)2-D3-binding profile was restored in mixtures after trypsin or heat treatment of the B95-8 extract. These data indicate that some New World primate cells contain a soluble protein that prevents intracellular 1,25(OH)2-D3-VDR binding. It is possible that the quantitative differences in the expression of this protein are responsible for 1,25(OH)2-D3 and other steroid hormone resistant states of variable severity in New World primates.

Animals↗

Diminished internalization and action of 1,25-dihydroxyvitamin D3 in dermal fibroblasts cultured from New World primates.

We investigated the occurrence of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-resistant osteomalacia in the New World primate colony of Saguinus imperator at the Los Angeles Zoo. The mean serum concentration of 1,25-(OH)2D3 was elevated 5-fold in the New World primates compared to that in their Old World counterparts. The specific internalization of 0.6 nM [3H]1,25-(OH)2D3 by cultured dermal fibroblasts from New World primates was reduced 75% compared to that by cells from Old World primates or man. The decrease in hormone uptake resulted from a decrease in the number of high affinity intracellular binding sites for 1,25-(OH)2D3 and apparently caused a 90-95% reduction in 1,25-(OH)2D3-induced 25-hydroxyvitamin-D3-24-hydroxylase activity. There was no alteration in the capacity or avidity of New World primate serum for 1,25-(OH)2D3 compared to that of serum from Old World primates. These data suggest that the occurrence of vitamin D-resistant osteomalacia in New World primates is the result of decreased high affinity, receptor-mediated uptake of 1,25-(OH)2D3 by the target cell.

Animals↗

Molecular evolution of GH in primates: characterisation of the GH genes from slow loris and marmoset defines an episode of rapid evolutionary change.

Pituitary growth hormone (GH), like several other protein hormones, shows an unusual episodic pattern of molecular evolution in which sustained bursts of rapid change are imposed on long periods of very slow evolution (near-stasis). A marked period of rapid change occurred in the evolution of GH in primates or a primate ancestor, and gave rise to the species specificity that is characteristic of human GH. We have defined more precisely the position of this burst by cloning and sequencing the GH genes for a prosimian, the slow loris (Nycticebus pygmaeus) and a New World monkey, marmoset (Callithrix jacchus). Slow loris GH is very similar in sequence to pig GH, demonstrating that the period of rapid change occurred during primate evolution, after the separation of lines leading to prosimians and higher primates. The putative marmoset GH is similar in sequence to human GH, demonstrating that the accelerated evolution occurred before divergence of New World monkeys and Old World monkeys/apes. The burst of change was confined largely to coding sequence for mature GH, and is not marked in other components of the gene sequence including signal peptide, 5' upstream region and introns. A number of factors support the idea that this episode of rapid change was due to positive adaptive selection. Thus (1) there is no apparent loss of function of GH in man compared with non-primates, (2) after the episode of rapid change the rate of evolution fell towards the slow basal level that is seen for most mammalian GHs, (3) the accelerated rate of substitution for the exons of the GH gene significantly exceeds that for introns, and (4) the amino acids contributing to the hydrophobic core of GH are strongly conserved when higher primate and other GH sequences are compared, and for coding sequences other than that coding for hydrophobic core residues the rate of substitution for non-synonymous sites (K(A)) is significantly greater than that for synonymous sites (K(S)). In slow loris, as in most non-primate mammals, there is no evidence for duplication of the GH gene, but in marmoset, as in rhesus monkey and man, the putative GH gene is one of a cluster of closely related genes.

Animals↗

[Is brain surgery on primates in basic research morally acceptable?]

In the contemporary controversy about the legitimacy of vivisection a few basic assumptions are shared by nearly all participants of the discussion. (I) Pure Research in the service of medicine is of great value for humankind. It contributes to prolonging human life and the alleviation and prevention of human suffering. (II) Brain surgery for the sole purpose of pure research is morally unacceptable in the case of any human being. (III) Primates are sensitive beings which lead a rich social life and are endowed with remarkable intellectual capacities. (IV) Primates have a moral standing, possibly to a lesser degree compared with human beings, certain acts are therefore an injustice toward them. The controversy then is about the question whether premise (I) outweighs (IV), i.e. whether the benefit of the pure research is from a moral point of view more important than the suffering of innocent primates. I shall present four arguments against such a conclusion. 1) According to premise (I) brain surgery on human beings for the sole purpose of pure research is morally unacceptable. Since this prohibition is meant to include all human beings it cannot rest on the exclusive human possession of reason because e.g. some mentally handicapped human beings lack this faculty. All other properties which may be named as basis for the ascription of a moral status which forbids brain surgery for pure research, are possessed also by some animals, especially primates; therefore it is impossible to deny them the same moral status. 2) Brain surgery on primates is confronted with an insoluble dilemma: If the characteristics of the primate brain are very similar to that of human beings, the scientific benefit is obvious, but the procedure appears to be morally unacceptable exactly because of this similarity. If, on the other hand, the characteristics differ significantly, brain surgery may seem legitimate but the scientific benefit becomes doubtful at best. 3) We could quite easily save hundreds of human lives if e.g. speed limits would be reduced (say) by half. Most of us, however, are unwilling to accept such a loss of quality of life in order to save a certain number of human lives. Since we are no prepared to pay this comparatively modest price, we have, in my eyes, no moral right to impose considerable pain and suffering on a primate to save human lives. 4) Pure research in the service of human medicine is from a moral point of view of great importance. Since most of the work in this area is done or financed by private corporations and not by state institutions, from a economical point of view the aim consists in making profit. Since the latter aspect has gained more and more weight in the last years the moral worth of pure research cannot rule out any other moral concern.

Journal Article↗

[Changes in nerve growth factor levels related to age and neurotrophic treatment in non-human primate].

INTRODUCTION: To examine the amounts and role of growth factors in different tissues and corporal fluid, new sensitive techniques have to be developed. A major problem is that the normal concentration of trophic substances, such as nerve growth factor (NGF), in central and peripheral nervous system and in fluids is very low (ng pg/ml). A valuable method of research is the sensitive two site enzyme immunoassay using the monoclonal antibody 27/21 to mouse NGF. Materials and methods. The present work applied this enzyme immunoassay to examine the NGF levels in normal non human primate sera (n= 94) and applied this assay to study of NGF levels in two non human primate receiving NGF infusion: one young and one aged. Two groups of non human primate sera were studied one young adult (n= 69) and one aged (n= 25). The serum samples NGF treated non human primate were taken before the infusion and at the 1st week and 1st, 3rd, 6th and 12th month after infusion. RESULTS: To further test the specificity of conjugate binding, dilutions of the non human primate sera were preincubated with an excess of monoclonal NGF antibody 27/21 in solution. With this strategy it was possible to completely block the signal obtained using the enzyme immunoassay. We found very low levels of NGF in aged monkeys (0.054 ng/ml) when compared with young adult group (0.152 ng/ml) (p> 0.01). The NGF levels in aged non human primate treatment with NGF was very low before (0.50 ng/ml) and during NGF treatment evolution time, whereas at the the 12th month showed an increase in NGF levels (0.180 ng/ml). We found normal values of NGF in the young monkey before and during the first year after NGF infusion. CONCLUSIONS: Using the enzyme immunoassay described it is possible to know the serum concentration of NGF immunoreactive in non human primate and this assay is able to detect peripheral changes in NGF levels after intracerebral infusion of NGF.

Age Factors↗

Enteric viruses of nonhuman primates.

The phylogenetic relationship of nonhuman primates to man implies that many of these animals could serve as surrogates for studies of diseases of man. Many nonhuman primate species are susceptible not only to viruses of human origin but also to nonhuman primate viruses that are counterparts of viruses of man. All monkeys and great apes do not respond similarly to an antigenic stimulus. Some agents are highly pathogenic for one species and completely innocuous for another. For example, poliovirus causes disease and fatalities in great apes, but picornaviruses given orally cause few lesions in most nonhuman primates. Other enteroviruses (coxsackie-, echoviruses) have caused disease in nonhuman primates. It is difficult to separate viruses into distinct categories according to their anatomic affinities. Many viruses not considered to be enteric may be recovered from the intestinal tract. Adenoviruses, both human and nonhuman strains, which are not considered enteric viruses, nonetheless are recovered frequently from the intestinal tract. Adult animals show little evidence of disease, with the possible exception of diarrhea, after adenovirus infection. Newborns, however, may respond with a fatal pneumoenteritis. Adenovirus may be associated with diseases in organs other than the intestines. The reoviruses, which may be recovered from the intestinal tract, also are generally innocuous. Rotaviruses as pathogens in nonhuman primates are presently under study, and it is suspected that rotaviruses of man may produce experimental disease in nonhuman primates. Production of diabetes by several of the enteric viruses has been suggested but not demonstrated conclusively.

Adenoviridae↗

Marburg and Ebola virus infections in laboratory non-human primates: a literature review.

BACKGROUND AND PURPOSE: Several non-human primate species are used as laboratory animals for various types of studies. Although importation of monkeys may introduce different diseases, special attention has recently been drawn to Marburg and Ebola viruses. This review presented here discusses the potential risk of these viruses for persons working with non-human primates as laboratory animals by focusing on epidemiology, virology, symptoms, pathogenesis, natural reservoir, transmission, quarantine of non-human primates, therapy, and prevention. CONCLUSION: A total of 23 Marburg and Ebola virus outbreaks causing viral hemorrhagic fever has been reported among humans and monkeys since the first outbreak in Marburg, Germany in 1967. Most of the 1,100 human cases, with nearly 800 deaths, developed in Africa due mainly to direct and intimate contact with infected patients. Few human cases have developed after contact with non-human primates used for various scientific purposes. However, adequate quarantine should be applied to prevent human infections not only due to Marburg and Ebola viruses, but also to other infective agents. By following proper guidelines, the filovirus infection risk for people working with non-human primates during quarantine exists, but is minimal. There seems to be little risk for filovirus infections after an adequate quarantine period. Therefore, non-human primates can be used as laboratory animals, with little risk of filovirus infections, provided adequate precautions are taken.

Animals↗

The relation between hand morphology and quadrupedalism in primates.

Primate hands can be classified into two broad categories on the basis of ray proportions and other features. Ectaxonic hands are characterized by a longer fourth ray and are found in most strepsirhines. Most haplorhines possess mesaxonic hands which are characterized by a longer third ray. Preuschoft et al. ([1993] in H. Preuschoft and D.J. Chivers (eds.): Hands of Primates. Berlin: Springer-Verlag, pp. 21-30) proposed a biomechanical model which predicts that, during quadrupedalism, a mesaxonic hand should be held in a more neutral position with respect to the forearm, whereas an ectaxonic hand should be more ulnarly deviated. The relation between hand positioning and the mesaxony/ectaxony categorization is investigated for 27 primate taxa. Videotapes were recorded for each species walking quadrupedally on arboreal supports. Several species were also videotaped during ground quadrupedalism. The degree of deviation of the hand relative to the substrate and the grips utilized were quantified for 18 species from the videotapes. Primates with mesaxonic hands use deviated hand positions and grips, especially when walking quadrupedally on small poles. Several species with ectaxonic hands use neutral hand positions and grips when walking quadrupedally on similar supports. Also, several primates, with either ectaxonic or mesaxonic hands, display a combination of deviated hand positions and grips when on arboreal substrates and neutral hand positioning when on the ground. The statistical results indicate that hand positioning during quadrupedal walking is more variable than expected based on the mesaxony/ectaxony classification. Furthermore, radiographic data suggest that primates evolved at least two different mechanisms of hand ulnar deviation.

Animals↗