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PubMed1988

Role of non-human primates in malaria vaccine development: memorandum from a WHO meeting.

This Memorandum discusses the coordination and standardization of malaria vaccine research in non-human primates to encourage optimum use of the available animals in experiments that are fully justified both scientifically and ethically. The requirements for experimentation in non-human primates, the availability of suitable animals for malaria vaccine studies, and the criteria for testing candidate vaccines are considered. The policy and legislation relevant to the use of non-human primates in biomedical research are also briefly discussed. The Memorandum concludes with eight recommendations.

Animal Welfare↗
PubMed1988

Prophylactic corticosteroid suppresses endotoxemia in heat-stressed primates.

We previously found that lipopolysaccharides (LPS) leak from the gut lumen into the hepatic portal vein during heat stroke. Furthermore, we found that prophylactic corticosteroid administration could prevent a rise in plasma LPS concentration in superior mesenteric artery occlusion shock. In this study, we found that treatment prior to heat-stress with corticosteroids could prevent any rise in plasma LPS concentration in heat-stressed primates. Two groups of primates, one of which received a prophylactic dose of methylprednisolone sodium succinate (MPSS) (n = 4) were subjected to heat-stress (41 +/- 0.3 degrees C). Their arterial blood pressure, heart rate and rectal temperature (Tr) were continuously recorded. In the untreated control group (n = 8), the plasma LPS concentration tended to increase slowly at a Tr of 41.5 degrees C from an initial 0.06 +/- 0.013 ng.ml-1. Above a Tr of 43 degrees C, the plasma LPS level rose rapidly until at a Tr of 44.4 +/- 0.1 degrees C, the mean LPS level was 0.315 +/- 0.03 ng.ml-1 (p less than 0.001). Prophylactic treatment with MPSS suppressed the increase in plasma LPS levels to 0.066 +/- 0.01 ng.ml-1 before heat-stress and 0.03 +/- 0.01 ng.ml-1 at Tr 44.4 degrees C just before primate demise. The mean arterial pressure of the control group was lower than the treated group for any given Tr; between Tr 42-43 degrees this difference was significant (p less than 0.05). Moreover, the cardiovascular parameters began to deteriorate at a lower Tr in the control group.

Animals↗
PubMedDate not supplied

[Morphological manifestations of primate adaptation to orthograde statics and upright posture].

Using lower primates (rhesus-monkeys) who were experimentally transformed to bipeds, we examined morphological signs of their musculo-skeletal adaptation to the upright walking pattern. It was found that the bipeds developed typical characteristics of the upright posture: complete erectness of the torso and legs and noticeable enhancement of lumbar lordosis. The maximum deviation of the lumbar arch in the bipeds (10.0 +/- 0.8 mm) was significantly greater than in the controls (1.5 +/- 0.5 mm). This was accompanied by distinct hypertrophy of leg muscles, primarily extensors, and increased mineral density of the tibia (by 38%), fibula (by 14%) and metatarsus (by 23%). This was also followed by slight hypotrophy of biceps and triceps muscles and the large muscle of the thorax. Forearm muscles and bone mineral content were unchanged. The data obtained give evidence that the genetic program of orthograde statics and erect posture which is typical of the entire primate order can find phenotypical realization in lower primates.

Adaptation, Physiological↗
PubMed1987

Sequence of reconstitution of seven basement-membrane components following split-thickness wound induction in primate skin.

Recent studies have shown an orderly sequence of expression of structural antigens within the skin basement-membrane zone of the human fetus. Interestingly, these findings differ from those reported following split-thickness would induction in Yorkshire pigs. To readdress this apparent disparity, as well as to further extend such studies to include other basement-membrane antigens more recently identified, we produced split-thickness wounds in a primate species and serially examined the wounds by immunofluorescence technique for the expression of seven antigens normally found in intact primate skin basement membrane. By the fourth day following wounding, laminin, type-IV collagen, and fibronectin were all detectable along the dermoepidermal junction. In contrast, bullous pemphigoid antigen, epidermolysis bullosa acquisita antigen, cicatricial pemphigoid antigen, and KF-1 antigen were undetectable until days 6, 8, 10, and 11, respectively. These latter findings are in complete agreement with those previously reported in the developing human fetus. On the basis of the results of this study, we would suggest that primate rather than pig skin may be a more appropriate animal model for wound-healing studies. These data are consistent with previous reports suggesting that the basement-membrane antigens recognized by bullous pemphigoid and cicatricial pemphigold autoantibodies are indeed distinct. Finally, these data bring into question the functional role of bullous pemphigoid antigen during the early phase of wound healing in humans.

Animals↗
PubMed1986

Host defense deficiency in newborn nonhuman primate lungs.

We have investigated two major aspects of the pulmonary host defense mechanism--alveolar macrophage function as a "first line of bacterial defense" and induced neutrophil migration into the lung as a "back-up defense." Chemotactic and phagocytic/killing assays revealed a functional deficiency in the alveolar macrophages of newborn primates. Serial bronchoalveolar lavage investigations revealed diminished neutrophil migration into the newborn primate lung. The overall pulmonary host defense capability in newborn primates was deficient. The results of this investigation may have direct clinical relevance to the susceptibility of newborns to infections and pneumonia.

Animals↗
PubMed1986

Inhibition of PAF-induced systemic responses in the rat, guinea pig, dog and primate by the receptor antagonist SRI 63-441.

Systemic administration of synthetic PAF produces a number of dose-dependent circulatory effects in a variety of species. We have evaluated a novel PAF antagonist, SRI 63-441, for its ability to inhibit PAF-induced effects in the rat, guinea pig, dog and primate. In the rat, a 100 ng kg-1 i.v. PAF challenge produced a (mean +/- 1 S.D.) 39 +/- 5% decrease in carotid blood pressure. Prior injection of SRI 63-441 inhibited this hypotensive response in a dose-dependent manner, with an ED50 of 0.15 mg kg-1 i.v. In the guinea pig, PAF at 100 ng kg-1 elicited a 50 +/- 8% increase in hematocrit and a 50 +/- 11% elevation in bronchial resistance. The ED50 values for inhibition by SRI 63-441 of these two physiological parameters were 0.012 mg kg-1 and 0.035 mg kg-1 i.a., respectively. Dogs challenged with 1.5 micrograms kg-1 PAF i.v. exhibited 28.7 +/- 6.5% increase in hematocrit 10 min after injection. The ED50 value for SRI 63-441 inhibition of hemoconcentration in the dog was 0.18 mg kg-1 i.v. In the primate model of PAF-induced hemoconcentration, controls responded to 3.5 micrograms kg-1 i.v. PAF with a 30 +/- 6% increase in hematocrit. Using the primates in a cross-over design, the ED50 of SRI 63-441 was 0.11 mg kg-1 i.v. At this ED50 value, the ratio of nmol kg-1 PAF used versus nmol kg-1 antagonist is approximately 1:25. The effectiveness of SRI 63-441 in these models suggest potential clinical applications in disease states involving hyperpermeability and pulmonary dysfunction.

Animals↗
PubMed1987

Comparison of epidural pressure in live anesthetized and post-mortem primates.

The response of the head to impact in the posterior-to-anterior direction was investigated with live anesthetized and post-mortem primates. The study was conducted at the University of Michigan Transportation Research Institute (UMTRI) under the sponsorship of the Motor Vehicle Manufacturers Association. 3-D motion and epidural pressures were experimentally measured. Interpretation of the results by simulating the tests using a 3-D mathematical model of the primate brain was done by Dr. C. Ward. The results of the tests and the simulation are presented to demonstrate the differences found between live and post-mortem primate brains.

Animals↗
PubMed1985

In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates: I. Effects of anti-T11 antibodies on the circulating T cell pool.

The effects of in vivo administration of three monoclonal antibodies specific for T11, the E rosette receptor on T lymphocytes, were examined in the rhesus monkey (Macaca mulatta). These three monoclonal antibodies were of different isotypes and were shown in in vitro studies to have differing affinities for the monkey T11 structure. Furthermore, each antibody induced antigenic modulation of T11 from the cell membrane of the lymphocytes to varying degrees in vitro. In vivo infusion of each of these antibodies into normal rhesus monkeys caused remarkably different effects on the circulating T lymphocyte pool. Infusion of these antibodies at doses of 2 mg/kg caused the coating of circulating T lymphocytes with antibody, the modulation of T11 off the T cell surface and the transient clearance of T cells from the circulation. Yet, the variation in the extent to which these effects were seen with these different antibodies indicates that extrapolating from studies of the in vivo use of one antibody to the use of another may be quite difficult. These studies clearly indicate the strengths of this nonhuman primate system for exploring the uses of monoclonal antilymphocyte antibodies as therapeutic agents. They, however, also demonstrate that differences may exist in the affinity of a particular antibody for homologous lymphocyte surface structures in humans and in a nonhuman primate species. These differences may make it difficult to predict the precise effects that the infusion of an antibody will cause in humans on the basis of alterations it induces in nonhuman primates.

Animals↗
PubMed1977

Host range characteristics of the primate coccidian, Isospora arctopitheci Rodhain 1933 (Protozoa: Eimeriidae).

Studies were conducted on 35 primates, 12 carnivores, and 2 marsupials to determine their susceptibility to the primate coccidian, Isospora arctopitheci. Patent oocyst infections resulted in 12 of the 14 species of animals investigated. These included 6 genera of New World primates native to Panama: Saguinus geoffroyi, Aotus trivirgatus, Ateles fusciceps, Cebus capucinus, Alouatta villosa, and Saimiri sciureus. In addition 4 families of carnivores (2 domestic and 2 sylvatic) and 1 species of marsupial became infected following experimental exposure. These animals are represented respectively by the following 6 genera and species: Canis familiaris; Felis catus; Nasua nasua, and Potos flavus; Eiria barbara; and Didelphis marsupialis. Four Old World rhesus monkeys, Macaca mulatta, and 1 carnivore, Bassaricyon gabbii, did not become oocyst positive. This unusually large host range makes this isosporan unique among the coccidia that have been investigated to date.

Alouatta↗
PubMed1975

Testis antigens of man and some other primates.

Rabbit antisera raised aginst testis preparations of human, chimpanzee, rhesus monkey, and baboon origin were used to study testis-specific antigens within and among the four primate species. Antisera were absorbed with serum, liver, kidney, and spleen preparations of the respective species against which they had been produced. Immunoelectrophoretic analysis of testis extracts, using the absorbed antisera, indicated the following minimum numbers of testis-specific antigens for each species: man, 10; chimpanzee, 8; rhesus monkey, 10; and baboon, 8. Most of the testis antigens were cross-reactive among species. The results suggest that human spermatozoa possess at least four to five specific antigens which originate in the testis. The antigen that induces sperm-immobilizing antibody cross-reacted among the four species of primates. Human and rhesus monkey sperm reacted equally in the immobilization system. Testis extracts from each primate species were capable of removing the sperm-immobilizing activity of human immune sera by absorption. Testis proteinase activity, as determined by using a gelatin membrane substrate, was inhibited by the gamma-glogulin fractions of rabbit and rhesus monkey antisera and also appeared to be cross-reactive among the species.

Animals↗
PubMed1982

The pathoparasitology of the alimentary tract and pancreas of nonhuman primates: a review.

A review of the literature concerning the gross and histologic lesions associated with protozoal and metazoal parasitism in the alimentary tract and pancreas of nonhuman primates is presented. In addition, the natural history, morphology, life cycle, methods for diagnosis, and potential for zoonotic disease are reviewed briefly for each parasite discussed. The parasite species reviewed in detail are those most common or most likely to produce lesions in the alimentary tract and pancreas of the nonhuman primate host. All parasites, both pathogenic and nonpathogenic, in each major group (protozoa: flagellates, sarcodines, sporozoans, neosporans, and ciliates; and metazoa: trematodes, cestodes, nematodes, acanthocephalans, and pentastomids) that have been reported in the nonhuman primate alimentary tract and pancreas are presented in tables.

Amebiasis↗
PubMed1984

Biological correlates of attachment bond disruption in humans and nonhuman primates.

Separations or disruptions in attachment bonds occur frequently in the social lives of humans and have been linked to the development of psychopathology. Separation of social nonhuman primates has been proposed as a model to study the psychological and biological effects of separation in humans. This paper reviews the biological alterations that occur in nonhuman primates undergoing separation and compares these with changes associated with separation in humans. The data reviewed demonstrate that separation in humans and nonhuman primates can be an event with profound behavioral and physiological sequelae.

Animals↗
PubMed1983

Primates--requirements by the pharmaceutical industry.

The use of primate animals by the pharmaceutical industry, emphasizing the species and number employed in the production and testing of biologics, is reviewed. The impact of the embargoes imposed by the resource countries is discussed, as well as the alternatives to the use of primates that are available to the pharmaceutical manufacturer. The paper concludes by considering the likely long-term effect of the curtailment of the supply of nonhuman primates from feral sources.

Animal Testing Alternatives↗
PubMed1984

Myopic correction using alloplastic implants in non-human primates--a preliminary report.

Hydrogel keratophakia has been studied in a non-primate model in an attempt to develop a more predictable form of myopic refractive surgery. Although the largest potential clinical use for this form of surgery is for the correction of myopia, currently available surgical techniques are not nearly as predictable as non-surgical devices such as spectacles and contact lenses. In this paper, hydrogel lenses, implanted in non-human primate corneas, were used for the first time to flatten the anterior corneal surface as would be required for the correction of myopia. Up to 9 diopters of correction was obtained. Little change in corneal astigmatism was found. The technical aspects of the surgery are quite simple, and the corneas healed rapidly and have excellent clarity. Extensive primate testing will be necessary to determine the accuracy of this procedure before clinical trials should be undertaken.

Animals↗
PubMed1981

Immunohistochemistry of vasopressin, oxytocin and neurophysin in the hypothalamus and extrahypothalamic regions of the human and primate brain.

Vasopressin, oxytocin and neurophysin were localized in the brains and spinal cords of four primates (tree shrew, squirrel monkey, rhesus monkey and human) using antisera to these peptides and the unlabelled antibody-enzyme peroxidase antiperoxidase method. Magnocellular neurons in the hypothalamus stained positively for vasopressin, oxytocin or neurophysin. Parvocellular neurons of the suprachiasmatic nucleus (SCN) stained positively for vasopressin and neurophysin but not for oxytocin, in all four species. Magnocellular oxytocin, vasopressin and neurophysin neurons project to permeable capillaries in the neurohypophysis, as well as to various extrahypothalamic neural target areas including the central amygdala, nucleus of the solitary tract, dorsal motor nucleus of the vagus, lateral reticular nucleus, dorsal horn, central grey and intermediolateral nucleus of the spinal cord. In target areas, terminals contact somata and dendrites. Parvocellular vasopressin and neurophysin neurons of the SCN do not project to the neurohypophysis, and project only to neural target areas, including the lateral septum, mediodorsal thalamus, lateral habenula, mesencephalic central grey, medial amygdala and ventral hippocampus. (Due to the relatively poor tissue preservation in human autopsy specimens not all projections found in the other primates could be confirmed in humans.) These findings confirm and correlate well with previous descriptions made in rodents, and indicate that vasopressin, oxytocin and neurophysin projections to neural targets are present in primates. Peptides released from these projections probably do not enter the bloodstream, but are rather involved in neural mechanisms.

Animals↗
PubMed1995

Pathology and immunohistochemistry of callitrichid hepatitis, an emerging disease of captive New World primates caused by lymphocytic choriomeningitis virus.

Callitrichid hepatitis is an arenavirus infection that recently emerged as a highly fatal disease of New World primates in the Callitrichidae family. As we previously reported, these primates develop hepatitis after contact with mice that are infected with variants of LCMV (LVMCCH), recently determined to have 86% identity with GC-P gene of the Armstrong and Western strains of LCMV. Here, we describe the histopathological lesions and tissue localization of viral antigens in confirmed cases of callitrichid hepatitis from recent outbreaks in two U.S. zoos. The liver in marmosets and tamarins with fatal infections consistently showed degeneration, necrosis, and inflammation, with variable involvement of the spleen, lymph nodes, adrenal glands, intestine, pancreas, and central nervous system. Lymphocytic choriomeningitis virus antigens were identified immunohistochemically in necrotic foci in these organs as well as in nondegenerating areas in lungs, kidney, urinary bladder, brain, and testes. The multi-organ tropism and histological pattern of LCMV infection in marmosets and tamarins are similar to those reported for the highly virulent arenavirus that causes Lassa fever in humans. Comparative studies of callitrichid hepatitis and Lassa fever would therefore be mutually beneficial for human and nonhuman primate medicine.

Animals↗
PubMed1995

Antigen-based heteropolymers facilitate, via primate erythrocyte complement receptor type 1, rapid erythrocyte binding of an autoantibody and its clearance from the circulation in rhesus monkeys.

We investigated the feasibility of using the primate E complement receptor (CR1), in concert with Ag-based heteropolymers (AHP), as a potential therapy to remove autoantibodies from the circulation. AHP are prepared by cross-linking an anti-CR1 mAb with the acetylcholine receptor (AChR), the principal target Ag in myasthenia gravis. In vitro studies demonstrate that this methodology facilitates specific, rapid, and quantitative binding of an anti-AChR mAb to primate Es. In vivo experiments in rhesus monkeys indicate that AHP-mediated binding of an anti-AChR mAb to Es leads to the clearance of the mAb from the circulation. Once bound to the E via the AHP, the autoantibody is transported to the liver and spleen, where it is degraded without destruction of the E. It is therefore likely that the complexes of AHP and target mAb, when bound to Es, are recognized in vivo and processed by a mechanism quite similar to that which occurs when complement-opsonized immune complexes, bound to primate Es, are cleared from the circulation. It may be possible to extend and generalize this work to allow for the development of a simple, noninvasive therapy that can be made specific for the treatment of several different autoimmune diseases.

Animals↗
PubMed1993

Anterior chamber-associated immune deviation elicited via primate eyes.

PURPOSE: To determine whether injection of a soluble antigen, ovalbumin (OVA), into the anterior chamber of cynomolgus monkey eyes would impair the ability of these animals to subsequently develop delayed hypersensitivity when confronted by this antigen in immunogenic form. METHODS: OVA or phosphate-buffered saline was injected into the anterior chamber of adult cynomolgus monkeys that were subsequently immunized with OVA in adjuvant and then skin challenged for delayed hypersensitivity with OVA. RESULTS: Recipients of intracameral OVA proved unable to acquire antigen-specific delayed hypersensitivity when they received an immunogenic regimen of OVA in adjuvant. Since the flow of aqueous humor through the uveoscleral pathway of primate eyes can be promoted by topical treatment with PGF2 alpha isopropylester, a preliminary experiment is described in which induction of anterior chamber-associated immune deviation by OVA was prevented when the antigen was first introduced into monkey eyes treated with PGF2 alpha isopropylester. CONCLUSIONS: Monkeys resemble rodents in displaying anterior chamber associated immune deviation (impaired ability to acquire antigen-specific delayed hypersensitivity) when they first encounter an antigen via the anterior chamber. The findings suggest that the cellular and molecular mechanisms of immune privilege, recently described in rodents, may apply to immune responses to intraocular antigens and pathogens in primates, including humans. Primate eyes offer an opportunity to explore the mechanisms of anterior chamber-associated immune deviation using pharmacologic agents that modify the aqueous outflow tracts.

Animals↗