Subhuman Primate Species Research Articles

OUR PROGRESS AGAINST POLIO - ERADICATION STILL REMAINS CHALLENGE

Polioviruses are enteroviruses that are transmitted direct from person to person or following excretion in feces or pharyngeal secretions. Because the poliovirus receptor is only expressed on human cells or on cells of few subhuman primate species, eradication is possible. In 1988 the Global Initiative for Polio Eradication (GIPE) at the 41st WHO summit announced that the main goal for 2000 is complete polio eradication. According the CDC reports the aim has not been reached yet, although the incidence of polio cases were decreased from 350,000 cases of wild polio virus in more than 125 endemic countries in 1988 to only 400 cases of polio reported in only 3 endemic countries (Nigeria, Afghanistan and Pakistan) in 2000. The last case of wild polio virus (wPV) was detected in 1997 in Serbia. In order to eradicate polio virus two vaccines are used- inactivated and live-attenuated polio vaccines. According to the studies oral polio vaccine has better efficacy and immunogenicity profile in comparison to inactivated polio vaccines, but due to safety reasons inactivated polio vaccine is now widely used (there is no risk of vaccine associated paralytic polio - VAPP and vaccine derived polio virus- VDPV). Although there are very effective and immunogenic vaccines available all over the world the polio eradication is not a simple project, in undeveloped and developing countries vaccines are not available, whereas in developed countries parents refused to vaccinate their children.

Protective immune responses to dengue virus infection and vaccines: perspectives from the field to the bench.

Protective immune responses to dengue virus infection and vaccines: perspectives from the field to the bench.

Monoclonal antibodies directed against human Rh antigens in tests with the red cells of nonhuman primates

Monoclonal antibodies against Rh related antigens on human red cells often crossreact with the red cells of the highest subhuman primate species. Depending on specificity of antibody, the species tested, and technique used, these reactions can be either species-specific or type specific. In tests with chimpanzee red cells, some of the latter type reactions have specificities related to the R antigen of the R-C-E-F blood group system of chimpanzee; specificities of some others seem to be unrelated to any known chimpanzee blood groups. Monoclonal anti-D reagents that give uniformly positive reactions with human D-positive (common and rare types) red cells, display wide individual differences in tests with chimpanzee blood. This indicates that there are minute structural variations of antibody molecules from one monoclonal anti-D antibodies apparently have no bearing on recognition of the D combining site on the human red cells, but come into play when in contact with chimpanzee rbcs. Some of the monoclonal antibodies directed against Rh and LW molecules are distinguished by unusually strong reactions with the red cells of the Old World monkeys (macaques and baboons), which is in contrast with negative or weak reactions of the same antibodies with the red cells of anthropoid apes and human bloods. One may recall, that polyclonal anti-Rh sera do not react with the blood of rhesus monkeys, the phenomenon that was the source of controversy surrounding the discovery of the rhesus factor of the human blood.

Induction of Metachromasia in Experimentally Induced Hyperplastic/Hypertrophic Changes in the Prostate of the Cynomolgus Monkey (Macaca Fascicularis)

Metachromasia has been shown to be a stromal marker for human benign prostatic hyperplasia (BPH). So far, it is not known whether comparable changes can be demonstrated in experimentally induced BPH in the dog or in a subhuman primate species. In the present study, the phenomenon of metachromasia could be demonstrated in the prostate of cynomolgus monkeys, too. The reaction was quantitatively intensified by the treatment with androstenedione—an aromatizable androgen which caused hyperplastic and hypertrophic changes—especially a stimulation of the smooth muscle—in the stroma of the prostate. Simultaneous treatment with the aromatase inhibitor 1-methyl-ADD prevented both the phenomenon of metachromasia and the stimulation of the stroma. In conclusion, it is not only possible to induce hyperplastic/hypertrophic changes in the prostate of a subhuman species by means of an aromatizable androgen but, in addition, this effect is accompanied by a phenomenon which is thought to be typical for human BPH suggesting the suitability of this type of experiment for the study of the factors involved in the pathogenesis of BPH.

On the feasibility of inducing tolerance in man: a study in the cynomolgus monkey.

Our previous work on the in vitro generation of cytotoxic T lymphocytes from the blood of 15-22-week-old fetuses, and on the induction of immunological tolerane in both radiation chimeras and neonatal mice, using T lymphocyte-depleted allogeneic bone marrow cells, has led us to believe that it should be possible to establish red cell chimerism in human fetuses by the infusion of allogeneic adult bone marrow cells. The essential prerequisite appears to be the removal of immunocompetent T lymphocytes from the bone marrow transplant, for new T cells generated from donor stem cells become tolerant to the histocompatibility antigens of the host's thymus and cannot, therefore, cause graft-versus-host disease (GVHD). Such an approach could be used in the treatment of fetuses diagnosed at an early stage as suffering from life-threatening inherited blood disorders. The experiments described here were designed to test this hypothesis in a sub-human primate species, Macaca fascicularis. Twenty-two cynomolgus monkeys received infusions of haploidentical (paternal) bone marrow between days 51 and 95 of gestation. There was no evidence of chimerism in animals inoculated after day 75 from mating. Eight out of 14 fetuses inoculated before day 70 were late intra-uterine deaths, four were hydropic and in one, histological confirmation of GVHD was obtained, indicating that tolerance can be induced at this time, as GVHD can occur only if donor cells survive. The T cell-depletion technique used here did not appear to prevent GVHD.

An improved immunogen for anti-human chorionic gonadotropin vaccine eliciting antibodies reactive with a conformation native to the hormone without cross-reaction with human follicle stimulating hormone and human thyroid stimulating hormone

Beta-subunit of human chorionic gonadotropin (hCG) was associated with α-subunit of ovine luteinizing hormone (OLH) to create a heterospecies dimer (HSD) which has a higher steroidogenic potency than the homologous dimer of αhCG and βhCG in the mouse Leydig cell bioassay. The properties and merits of the antibodies induced by this HSD and βhCG linked to carrier(s) were investigated in rodents and in a subhuman primate species. The antisera had, in both cases, high affinity for binding with hCG ( K a = 10 9–10 10 M −1). The mean (± S.E.M.) bioneutralization capacity as a percentage of immunoreactivity (determined by radioimmunoassay (RIA)) of the antibodies generated by the HSD-carrier in rats and bonnet monkeys was higher in comparison with those induced by βhCG linked to carrier (80 ± 2.3% vs. 63 ± 1.5% in rats, and 65 ± 1.9% for HSD vs. 44 ± 3.7% in monkeys). None of the sera gave any evidence of cross-reactivity with human follicle stimulating hormone (hFSH) and human thyroid stimulating hormone (hTSH).

Effect of aromatase inhibitors on the functional morphology of the pituitary gland of dogs and monkeys

It was the goal of our studies to investigate the role of androgens and/or estrogens for the regulation of the negative feedback mechanism as well as the regulation of secretion of prolactin in male dogs and a male subhuman primate species by means of the aromatase inhibitor 1-Methyl-ADD and/or the antiandrogen cyproterone acetate. Based on our results an important but not exclusive role of estrogens in the feedback control of gonadotropic secretion in the dog and the cynomolgus monkey has been suggested. Androgens appear to be involved too. As far as prolactin is concerned it was concluded that estrogens do not always and under all conditions stimulate prolactin in primates and in dogs and that androgens also appear to stimulate prolactin in male individuals.

A Biochemical Property Relating to Power Seeking in Humans

The disposition to seek power in a social arena is tied in this research to a biochemical marker, whole blood serotonin. This finding constitutes the first systematic evidence of any biochemical property in humans which differentiates power seekers from others. The disposition itself is given empirical content with the use of measures of three components of the Type A behavior pattern—aggressiveness, competitiveness, and drive—and of distrust and self-confidence. The statistical fit with serotonin is very good. This discovery echoes similar findings in a species of subhuman primates.

Further evidence from tryptic peptide analysis for heterogeneity among type D retroviruses.

Tryptic peptide analyses were performed on the major internal structural proteins of type D retroviruses isolated originally from subhuman primate species (MPMV, SMRV, LV) and from permanent human cell lines (HeLaV, HEp-2V, PMFV). The p25 peptide maps of MPMV, LV, PMFV and HEp-2V were very similar but showed a striking dissimilarity to the p25 map of HeLaV and the p35 map of SMRV. All type D viruses included in this study could be distinguished by peptide maps of at least two of their three low-molecular-weight proteins p10, p12 and p15. These studies further demonstrate the heterogeneity among type D retroviruses.

Effect of immunization of a subhuman primate species against zona pellucida on hormonal profiles and fertility

One hundred and fifteen infertile men were examined for circulating spermagglutinating antibodies by the Kibrick spermagglutination test; thirty-three (28%) were found to have positive agglutination titers—1:32 or more in thirteen samples. This high figure may be explained by the high incidence of genital tract infection and of urinary schistosomiasis in our study group. Of the 33 men who demonstrated autoantibodies in their sera, 21 had microscopic agglutination of more than 10%. There was a positive correlation between the serum autoantibody titer and spermagglutination. Eight cases (6.9%) of sperm-immobilizing antibodies were found.

Observation d'un syndrome photomyoclonique chez Macaca nemestrina

Out of a group of 12 M. nemestrina (originating from Malaysia), 9 adults had shown clinical signs induced by ILS at 25 c/sec. Six of them (3 males, 3 females) were very photosensitive; however, only 2 presented eyelid and/or head jerks after the end of ILS (level 4), but never a generalized seizure. Tactile periorbital stimuli favoured myoclonus. In all but the two of level 4, the intensity of clinical signs varied from one day to the next. In all implanted adult macaques, spontaneous paroxysmal EEG activities were seen during slow sleep in mostly anterior areas, but also during waking and REM sleep in some of them; however, their occurrence depended upon the individual and were not in all cases related to their level of photosensitivity. During ILS, paroxysmal discharges (spikes and waves and/or polyspikes and waves), isolated or in bursts at 3-4/sec were bilateral and symmetrical. They started in fronto-rolandic regions, then became generalized. This observation constitutes a new fact since the discovery, in 1966, of the photomyoclonic syndrome of Papio papio, Macaca nemestrina being another species of subhuman primates with a marked predisposition to photosensitive epilepsy.

Colonic electrolyte flux and gut composition as seen in four species of sub-human primates

1. 1. Studies compare the composition of gastrointestinal contents and transmucosal electrolyte flux in four species of subhuman primates. 2. 2. The bushbaby, an insectivore, had significantly drier stomach contents, potassium and chloride concentration than the baboon, vervet or sykes monkey. 3. 3. While the caecum of all primates appeared to be the major site of microbial fermentation, the sykes monkey, a herbivore, indicated the highest level of stomach fermentative activity. 4. 4. Transmucosal electrolyte flux occurred primarily within the proximal colon of the baboon, vervet and sykes monkey. 5. 5. Volatile fatty acids were absorbed from the proximal colon of these animals.

Plasma carnitine and cholesterol levels in monkeys and pigeons: Species/breed differences and the influence of gender and diet

1. 1. Total plasma carnitine and cholesterol were studied in two breeds of pigeon and four species of sub-human primates. 2. 2. The levels of plasma carnitine and cholesterol differed within species and between species and were influenced by diet and gender. 3. 3. In the animals studied, pigeons had the highest levels of plasma carnitine ( > 120 nM/ml ) and Squirrel monkeys ( Saimiri sciureus) had the lowest levels ( ca. 10 nM/ml). 4. 4. Linear regression analysis of plasma carnitine and cholesterol in the monkeys and pigeons indicated no strong correlation between these parameters.

Metabolism of pregnenolone and progesterone by testicular microsomes of the baboon Papio anubis and the marmoset Saguinus oedipus

We recently reported that pregnenolone is converted to testosterone through a predominant 4-ene pathway by marmoset and baboon testicular fragments. The present studies were conducted to investigate the metabolism of pregnenolone and progesterone to testosterone by testicular rnicrosomes from these subhuman primate species. Marmoset and baboon testes were homogenized in Tris-sucrose buffer. The homogenates were centrifuged for 20 min at 10,000 g, and the supernatants re-centrifuged at 105,000 g for l h. The microsomal pellets were re-suspended in Tris-sucrose buffer and incubated for l h with radiolabelled pregnenolone or progesterone. Marmoset and baboon testicular microsomes converted pregnenolone to testosterone primarily through the 5-ene pathway, with an accumulation of 17-hydroxypregnenolone and dehydroepiandrosterone in the incubates. Progesterone was metabolized to 17-hydroxy progesterone, androstenedione and testosterone, but a substantial portion of the progesterone substrate was not metabolized. Estradiol and estrone were tentatively identified as metabolites of both substrates in marmoset and baboon testicular microsomes. These results suggest that homogenization of testicular tissue for preparation of testicular microsomes may activate a pregnenolone 17-hydroxylase, with pregnenolone being converted to testosterone through a predominant 5-ene pathway.

Substrate specificity for androgen biosynthesis in the primate testis

The metabolism of selected substrates of the 4-ene and 5-ene pathways was investigated in the testis of the marmoset Sanguinus oedipus. Testicular fragments (50 mg) were incubated in duplicate with 10μCi of the following radiolabeled substrates: pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, and testosterone. Incubations were for 3 h in Krebs-Ringer bicarbonate buffer, pH 7.4, at 37°C. Pregnenolone was converted to 17-hydroxy-progesterone (44.6)%, with lower conversion to testosterone (21.3%), androstenedione (10.8%), and progesterone (9.5%). Progesterone was metabolized to 17α-hydroxyprogesterone (47.3%) with testosterone (22.8%) and androstenedione (11.1%) identified in the incubates. 17-Hydroxypregnenolone was converted to testosterone (57.0%), dehydroepiandrosterone (22.1%) and androstenedione (13.6%). However, 17-hydroxyprogesterone was not well metabolized as 59.8% of the substrate remained, while testosterone and androstenedione were 21.2% and 10.7% of the respective radioactivities. Dehydroepiandrosterone was converted to testosterone (61.0%), and androstenedione (16.2%). Androstenedione was metabolized to testosterone (83.0%), while testosterone substrate was primarily nonmetabolized (85.4%), with some conversion to androstenedione (6.6%). These results suggest a predominant 4-ene pathway in marmosets due primarily to a lack of pregnenolone 17α-hydroxylase activity, while C 17-C 20 lyase may be the rate-limiting step for testosterone synthesis in the testis of this subhuman primate species.

Immunological Relationships of Human and Subhuman Primate Pregnancy-Associated Plasma Proteins

(1) Four pregnancy-associated plasma proteins cross-reactive with antibodies to the human pregnancy proteins were detected in several species of pregnant subhuman primates. In the case of the two apes studied (chimpanzee and orangutan), these appeared to be immunologically identical to the human PAPPs (PAPP-A, -B, -C, and HCS). In the old world monkeys analyzed, equivalent partially cross-reactive PAPPs were found; while in the new world squirrel monkey, only faint traces of cross-reactive PAPP-C and HCS were observed with the most sensitive methods used. (2) As in the human, these proteins appeared to be specific for pregnancy, not being detectable in nonpregnant animals, female or male. (3) The pregnant chimpanzee possessed significantly higher concentrations of PAPP-A and PAPP-C than did women at an equivalent stage of pregnancy, while the HCS and PAPP-B levels appeared to be approximately the same. (4) The primate PAPP-C analogues were more complex than human PAPP-C, often revealing multiple gel diffusion patterns with subfractions of differing electrophoretic mobilities. (5) Based on the changes of electrophoretic mobility upon exposure to neuraminidase, the subhuman primate as well as human PAPP-A and PAPP-C appeared to be glycoproteins containing sialic acid. (6) In the chimpanzee and rhesus monkey, as in the human, the levels of PAPP-A, PAPP-C, and HCS were appreciably higher during the third trimester of pregnancy than they were during the second trimester.

Primates and Political Authority: A Biobehavioral Perspective

This paper presents an evolutionary-biological perspective on the stratification of political authority, power, and influence. The rudiments and relevance of a biobehavioral approach are indicated, particularly in regard to study of the behavior of subhuman primate species. Dominance-deference behavior patterns in four species—rhesus macaques, savanna baboons, gorillas, and chimpanzees—are described and compared, followed by discussion of some stratification concepts that have been derived from primate studies and applied to human societies. The possible continuing influence on man's behavior of his evolutionary history is considered through discussion of a zoologist's attempt to reconstruct it, and through tentative reinterpretations of social psychological conceptions of leader-follower relationships and dispositions to obey authority figures. Finally, it is suggested that the modern conception of political authority per se as contingent and contrived may be empirically untenable, and, if so, that certain implications may follow concerning theories of political obligation and constitutionalism.

Phylogeny of Complement Components in Non-Human Primates

The antigenic properties and functional activities of complement components were analyzed in primates to determine their relative evolutionary development. The sera of eight different sub-human primate species were examined by double diffusion in agar and compared to a pool of human serum with rabbit and goat antisera to human complement components Clq, Cls, C4, C2 C3, C5, C6, C8, C9, properdin, factor B (B), and C1 inhibitor. There are no apparent antigenic differences in complement proteins between man and the apes except for C1q. Old world monkeys are antigenically deficient in Clq,C1s, C9, and variably deficient in C4, C3, and C8. New World monkeys are antigenically deficient in all components (measured) except C5, C6, and properdin factor B. Prosimians are antigenically deficient in all components. Functional analyses of complement components showed similar levels in man and primates, except in prosimians. There is a dissociation between hemolytic assays and antigenic analyses, suggesting that functional sites may be separate from antigenic sites.

On Diploid Cell Lines 1 2

Several types of tissues (lung, kidney, bone marrow, and skin) from 2 subhuman primate species, the rhesus macaque and the African green monkey, were used to initiate primary cultures and propagated in vitro to determine the feasibility of the establishment of "longterm" diploid cell lines.. Most skin lines can be propagated for over 40 subculture generations (passages) and maintain a chromosome constitution like that of the primary cultures. Instead of reliance on a single cell source such as the WI-38 line, more diploid cell lines from human and subhuman primate sources should be made available for biomedical research and for pUblic health work.

Comparison of phospholipid indicators of fetal lung maturity in the amniotic fluid of the monkey (Macaca mulatta) and baboon (Papio papio)

The pregnancies of two subhuman primate species, the monkey (Macaca mulatta) and the baboon (Papio papio), were examined to determine if either is a model for human fetal lung development as reflected in amniotic fluid studies. From the data, we suggest that the pregnant rhesus monkey is a model for the study of human lung development. The biochemical pathways for surfactant are the same; the concentrations of lecithin in amniotic fluid correspond closely; there is a parallel rise in L/S ratios which correspond, and the lecithin acyl ester structures and their changes during gestation are very similar. The presence of chronic stress is associated with acceleration of maturation of the surfactant systems of the lung. Although there are some analogies in baboon pregnancy, important differences in lecithin pathway timing and lecithin acyl ester structures make extrapolation to the human subject less tenable. Ligation of the monkey fetal trachea in the second trimester results in oligohydramnios without apparent lung distention. At delivery, the normal changes with age in surfactant biochemistry are not found in the amniotic fluid but are present in lung-bronchial tree washes.