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Data on social changes in patas monkey (Erythrocebus patas) groups were collected to clarify the general characteristics of male supplantation and to evaluate the overall role of supplanting in patas society. Seven patas groups were observed in Kala Maloue National Park, Northern Cameroon for 11 years. Analysis of this data revealed that social change, such as male supplanting, was restricted to the mating season. Male supplanting occurred in the course of outsider males seeking to gain access to estrous females within the heterosexual group and supplanting was inevitably followed by a multi-male situation arising in the group. Many cases of multi-male invasion were preceded by the supplanting of resident males and the multi-male situation arose due to a temporary absence of serious aggression towards invader males by the new resident males. Notably, an all-male group was found only once and it did not contribute to the supplanting of resident males in the one-male group.

We studied responses to alarm calls of sympatric patas (Erythrocebus patas) and vervet (Cercopithecus aethiops) monkeys in relation to habitat structure, with the intention of understanding the relationship between the environment and predator avoidance. Patas and vervet monkeys are phylogenetically closely related and overlap in body size. However, while patas monkeys are restricted to nonriverine habitats at our study site, vervets use both nonriverine and riverine habitats, allowing us to "vary" habitat structure while controlling for effects of group size, composition, and phylogeny. Patas monkeys in the nonriverine habitat responded to mammalian predator alarm calls with a greater variety of responses than did vervets in the riverine habitat, but not when compared with vervets in the nonriverine habitat. Ecological measurements confirm subjective assessments that trees in the riverine habitat are significantly taller and occur at lower densities than trees in the nonriverine habitat. Despite the lower density of trees in the riverine habitat, locomotor behavior of focal animals indicates that canopy cover is significantly greater in the riverine than the nonriverine habitat. Differences in responses to alarm calls by the same groups of vervets in different habitat types, and convergence of vervets with patas in the same habitat type, suggest that habitat type can be a significant source of variation in antipredator behavior of primates.

To understand the mitochondrial mechanisms underlying the lactic acidosis and hepatic steatosis seen in some HIV-1-infected individuals after long-term stavudine (d4T) exposure, we have explored mitochondrial integrity in adult monkeys (Erythrocebus patas) given a daily human equivalent dose of d4T for 78 days.Three Erythrocebus patas (patas) monkeys were given 3 mg d4T orally twice daily (total 6 mg d4T), or approximately 1.2 mg d4T/kg body weight per day, for 78 days and compared with 3 unexposed animals. Blood taken from controls and from treated monkeys before and after drug exposure was subjected to a complete clinical chemistry profile. Liver and skeletal muscles were examined for oxidative phosphorylation enzyme specific activities, mitochondrial deoxyribonucleic acid (mtDNA) quantity by slot blot, and mtDNA integrity by Southern blot.Clinical chemistry assays demonstrated few significant differences; however, one d4T-exposed monkey had a serum lactate of 8.1 mmol/L after 78 days of oral d4T ingestion. Specific activities of oxidative phosphorylation Complexes I, II, and IV were significantly altered in both livers and skeletal muscles from the d4T-exposed animals, compared with the controls (por = 0.05). Significant depletion of mitochondrial DNA was observed in livers of drug-exposed monkeys, but not in skeletal muscle (por = 0.05). Further examination of liver DNA by Southern blot confirmed hepatic mtDNA depletion in drug exposed animals.The data suggest that direct examination of the liver may be required to elucidate clinical d4T-induced hepatotoxicity related to mitochondrial damage.

A distinct subpopulation of neurons forming long corticocortical projections in the association neocortex is highly vulnerable to the degenerative process in Alzheimer’s disease. However, the degree to which age-related molecular and morphologic alterations of identifiable neuronal populations reflects early cellular degeneration leading to functional deficits has not yet been fully investigated in the aging brain. We performed an immunohistochemical analysis of neurons forming short and long corticocortical projections in young and old monkeys using antibodies to the GluR2 and NMDAR1 glutamate receptor subunit proteins. Projection neurons differed in their expression of these receptor subunits, as GluR2 was less prevalent than NMDAR1 among retrogradely labeled neurons. Long and short corticocortical pathways in old animals demonstrated a considerable decrease in the proportions of projection neurons containing GluR2 and NMDAR1, an observation that was particularly consistent in the case of GluR2. No age-related differences were observed in distribution of neurofilament protein in either type of projection neurons. These data suggest that cortical neurons furnishing long and short corticocortical projections display consistent neurochemical changes during aging and that a differential decrease in cellular expression of glutamate receptor subunit proteins occurs. The fact that in aging these neurons have lower levels of GluR2 than in young individuals, but comparatively higher levels of NMDAR1 than GluR2, may render them prone to calcium-mediated excitotoxicity, which in humans may be related to the selective vulnerability of such neurons during the course of Alzheimer’s disease. Also, it is apparent that age-related neuronal changes are quite subtle and involve subcellular components of the cortical circuits rather than major morphologic alterations.

The decay accelerating factor (DAF, CD55) protects self cells from activation of autologous complement on their surfaces. It functions to disable the C3 convertases, the central amplification enzymes of the cascade. Its active site(s) are contained within four approximately 60 amino acid long units, termed complement control protein repeats (CCPs), which are suspended above the cell surface on a 68 amino acid long serine/threonine (S/T)-rich cushion that derives from three exons. We previously proposed a molecular model of human DAF's four CCPs in which certain amino acids were postulated to be recognition sites for the interaction between DAF and the C3 convertases. In the current study, we characterized DAF in five non-human primates: the great apes, gorilla and common chimpanzee, and the Old World monkeys: hamadryas baboon, Rhesus macaque, and patas monkey. Amino acid homology to human DAF was approximately 98% for the two great apes and 83% for the three Old World monkeys. The above cited putative ligand interactive residues were found to be fully conserved in all of the non-human primates, although there were amino acid changes outside of these areas. In the chimpanzee, alternative splicing of the S/T region was found potentially to be the source of multiple protein isoforms in erythrocytes, whereas in the patas monkey, similar alternative splicing was observed but only one protein band was seen. Interestingly, a Rhesus macaque was found to exhibit a phenomenon paralleling the human Cromer Dr(a-) blood group, in which a 44-base pair deletion in CCP3 leads to a frameshift and early STOP codon.

3'-azido-3'-deoxythymidine (AZT) is given to pregnant women positive for the human immunodeficiency virus type 1 (HIV-1) to reduce maternal-fetal viral transmission. To explore fetal mitochondrial consequences of this exposure, pregnant Erythrocebus patas monkeys were given daily doses of 1.5 mg (21% of the human daily dose) and 6.0 mg (86% of the human daily dose) of AZT/kg body weight (bw), for the second half of gestation. At term, electron microscopy of fetal cardiac and skeletal muscle showed abnormal and disrupted sarcomeres with myofibrillar loss. Some abnormally shaped mitochondria with disrupted cristae were observed in skeletal muscle myocytes. Oxidative phosphorylation (OXPHOS) enzyme assays showed dose-dependent alterations. At the human-equivalent dose of AZT (6 mg of AZT/kg bw), there was an approximately 85% decrease in the specific activity of NADH dehydrogenase (complex I) and three- to sixfold increases in specific activities of succinate dehydrogenase (complex II) and cytochrome-c oxidase (complex IV). Furthermore, a dose-dependent depletion of mitochondrial DNA levels was observed in both tissues. The data demonstrate that transplacental AZT exposure causes cardiac and skeletal muscle mitochondrial myopathy in the patas monkey fetus.

I examined seasonal, sex, and interspecific differences in activity time budgest and diets of patas (Erythrocebus patas) and sympatric tantalus monkeys (Cercopithecus aethiops tantalus) on the basis of 5-day data sets collected in three and two different seasons, respectively, by the method of focal animal sampling. The seasons included species-specific mating and birth seasons. As compared with not only the birth season but also conspecific females, both patas resident male and tantalus male spent less time feeding and more time resting, day and night, in their respective mating seasons. Given that day-resting time includes time for vigilance for non-resident males and receptive females, this may reflect that males should minimize time spent feeding to allow maximum participation in other fitness-increasing activities such as mating-relating activities asSchoener (1971) predicted. In both species, the males consumed fruits containing less protein but more calories and showed a high feeding rate to compensate for the shorter time spent feeding in the mating season. In contrast, females consumed protein-rich food types (i.e. animals, protein-rich seeds, leaves, and flowers) in the birth season to meet the high demand for protein due to pregnancy and lactation. Given that the season for males was considered to be not a calendar but a reproductive “season” (i.e. mating or birth season), both sexes of patas spent more time moving and less time day- and night-resting than did the tantalus counterparts irrespective of the “season”. Patas subsisted on fruits, gums, and supplementarily lipid-rich seeds as an energy source and animal matters and protein-rich seeds as a protein source. In contrast, tantalus subsisted on fruits and lipid-rich seeds as energy and flowers and leaves as protein.

The expression of telencephalic reelin (Reln) and glutamic acid decarboxylase mRNAs and their respective cognate proteins is down-regulated in postmortem brains of schizophrenia and bipolar disorder patients. To interpret the pathophysiological significance of this finding, immunoelectron microscopic experiments are required, but these cannot be carried out in postmortem human brains. As an alternative, we carried out such experiments in the cortex of rats and nonhuman primates. We found that Reln is expressed predominantly in layer I of both cortices and is localized to bitufted (double-bouquet), horizontal, and multipolar γ-aminobutyric acid-ergic interneurons, which secrete Reln into extracellular matrix. Reln secretion is mediated by a constitutive mechanism that depends on the expression of a specific signal peptide present in the Reln carboxy-terminal domain. Extracellular matrix Reln is found to aggregate in proximity of postsynaptic densities expressed in apical dendrite spines, which include also the α 3 subunit of integrin receptors. Most pyramidal neurons of various cortical layers express the mouse-disabled 1 (Dab1) protein, which, after phosphorylation by a soluble tyrosine kinase, functions as an adapter protein, probably mediating a modulation of cytoskeleton protein expression. We hypothesize that the decrease of neuropil and dendritic spine density reported to exist in the neocortex of psychiatric patients may be related to a down-regulation of Reln–integrin interactions and the consequent decrease of cytoskeleton protein turnover.

Clinical, pathological, immunological, and virological evidence suggests that simian varicella virus (SVV) infection of primates is the counterpart of varicella-zoster virus infection of humans. To determine whether these two viruses share similarities in their properties during latency, we analyzed ganglia and brain of an African green monkey experimentally infected with SVV for the presence of viral nucleic acid using the polymerase chain reaction technique. We detected SVV DNA in dorsal root ganglia but not in brain of this monkey, which demonstrated no apparent clinical signs of SVV infection. Our results suggest that SVV becomes latent in monkey ganglia and that latency can develop in the absence of clinical varicella (chickenpox). These studies provide an animal model system to study varicella virus latency.

The metabolism of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was investigated in short-term cultures of monkey lung. Explants from the lungs of two patas monkeys (Erythrocebus patas) and one cynomolgus monkey (Macaca fascicularis) were incubated with 10 microM [5-(3)H]NNK and aliquots were analyzed for NNK metabolites by HPLC at various time points from 1 to 24 h. F344 rat lung tissue metabolism of NNK was assayed under the same conditions. Substantial amounts of metabolites from the alpha-hydroxylation metabolic activation pathway were detected in all cultures. In two of the monkey lung cultures, these metabolite levels were significantly higher than those formed by other pathways. All cultures also metabolized NNK by pyridine-N-oxidation and carbonyl reduction. The metabolism of NNK by cultured monkey lung was generally similar to that observed in rat lung, indicating that there are not major species differences between rodents and nonhuman primates in pulmonary metabolism of NNK.

In order to obtain reliable evidence for differences in habitat preferences between two closely related savanna-dwelling primate species, namely, patas monkeys (Erythrocebus patas) and tantalus monkeys (Cercopithecus aethiops tantalus), I collected data on vegetation and patterns of range use concurrently at a single study site, Kala Maloue, Cameroon, in a similar manner for a group of each species. Kala Maloue consisted of 64% grassland mostly dominated by Gramineae spp. and the rest was woodland. Tantalus monkeys showed preference for woodland, especially gallery forest, much more than did the patas irrespective of the season. Moreover, patas preferentially established their home range in grassland in the wet season. Interspecific and seasonal differences in habitat preferences could be interpreted on the basis of interspecific and seasonal differences in preferences for main food. In dry season, tantalus utilized water-containing areas at a frequency closely in proportion to the availability of such areas while the patas utilized water-containing areas more frequently than expected. This is because tantalus established a smaller home range along the river where water was never completely depleted throughout the dry season. Both the patas and the tantalus preferred woodland to grassland as sleeping sites possibly owing to predation avoidance. Both the daily travel distance per group weight and the home range size per group weight were greater for patas than for tantalus partly because of higher preference for grassland with low habitat quality in the case of patas. It is suggested, however, that high locomotive ability enabled patas to effectively utilize small and widely dispersed items of food such as grasshoppers and to explore areas with high availability of food and water and with preferable sleeping sites.

Herpesvirus simiae (B virus) occurs naturally in Asian macaques, particularly rhesus, bonnet, and cynomolgus monkeys 7,8 The term B virus was coined after a physician (W.B.) died from encephalitis 3 days after being bitten by a clinically normal rhesus monkey. Herpesvirus simiae was isolated from the patient’s brain, medulla, spinal cord, and spleen. The B virus is well adapted to its natural simian host, frequently causing only transient, mild oral lesions. Like many herpesviruses, a latent form occurs in recovered animals, and the virus can be recovered from kidney, oral secretions, and the trigeminal ganglia in clinically normal monkeys. Infected animals may not show clinical signs or have detectable antibody to the B virus. Surveys of wild and captive monkeys reveal a high variability in B virus infection rates. Approximately 10% of young recently captured animals were seropositive for B virus, whereas 70-80% of adults had positive titers. In addition to age, population density also influenced the number of positive animals. In Indonesia, 77% of those monkeys tested had positive titers, in Malaysia, 64%, and in the Philippines, 28%. Sera obtained from various laboratories utilizing primates revealed approximately 19% of the animals tested had antibody titers to B virus. The major interest in B virus has been the disease it causes in humans. Infected individuals develop an almost invariably fatal ascending myelitis and encephalitis. Fatal disease suspected to be caused by B virus has been reported in patas and colobus monkeys. This report describes a case of fatal B virus infection in a pet patas monkey. An adult male patas monkey was submitted for necropsy following a brief illness. The monkey had been normal the previous morning, yet developed anorexia and lethargy the evening prior to its demise. The monkey had been purchased from an unknown dealer in Missouri 3 weeks previously. He had been housed in an outside enclosure until 1 week prior to his death, when he was moved into an 8x 12x 6-foot indoor cage located in the basement of a house. There were 2 pairs of rhesus monkeys also in the basement. Their cages were separated from the patas monkey’s cage by a solid partition. All cages were cleaned at 2-3-day intervals. The patas monkey’s cage had never been used for holding other primates. All monkeys were fed a commercial diet formulated for primates and supplemented with various fruits. The patas monkey was fed an all fruit diet for 1 week prior to his death.

Patas monkeys were twice immunized with a #Schistosoma haematobium$-derived recombinant glutathione S-transferase (Sh28GST) then challenged with an homologous calibrated challenge. BCG and Freund's Complete Adjuvant (FCA) were used as adjuvants in two distinct protocols. Specific IgC and IgA antibody responses were intense and homogeneous in the animals receiving Sh28GST in the presence of FCA, whereas BCG could only induce moderate and heterogeneous antibody titres. No significant effect on worm burdens was evidenced 36 weeks post-infection in either group of Sh28GST-immunized animals compared to their matched controls receiving an irrelevant protein. Although not significant, 50% reductions in the numbers of eggs located in all tissues (FCA group) and in the urogenital system (BCG group) were noted. Moreover, the total number of excreted eggs was dramatically diminished by 60% and 77% in the BCG and FCA groups, respectively. These reductions reached 75% and 80% in the urines of vaccinated monkeys. Bladder pathology was also reduced in the animals displaying the lowest urinary egg excretions. There was no clear positive or negative correlate between antibody responses and individual levels of protection. Taken as a whole, our results show that Sh28GST was capable of significantly reducing #S. haematobium$ worm fecundity in experimentally infected primates. Although FCA induced higher levels of protection, the efficacy of BCG as an adjuvant appeared sufficient to justify consideration of the future application of this new formulation as a vaccine against human urogenital schistosomosis. (Résumé d'auteur)

Recently we reported the characterization of simian immunodeficiency virus (SIVlhoest) from a central African l’hoest monkey ( Cercopithecus lhoesti lhoesti ) that revealed a distant relationship to SIV isolated from a mandrill (SIVmnd). The present report describes a novel SIV (SIVsun) isolated from a healthy, wild-caught sun-tailed monkey ( Cercopithecus lhoesti solatus ), another member of the l’hoest superspecies. SIVsun replicated in a variety of human T-cell lines and in peripheral blood mononuclear cells of macaques ( Macaca spp.) and patas monkeys ( Erythrocebus patas ). A full-length infectious clone of SIVsun was derived, and genetic analysis revealed that SIVsun was most closely related to SIVlhoest, with an amino acid identity of 71% in Gag, 73% in Pol, and 67% in Env. This degree of similarity is reminiscent of that observed between SIVagm isolates from vervet, grivet, and tantalus species of African green monkeys. The close relationship between SIVsun and SIVlhoest, despite their geographically distinct habitats, is consistent with evolution from a common ancestor, providing further evidence for the ancient nature of the primate lentivirus family. In addition, this observation leads us to suggest that the SIVmnd lineage should be designated the SIVlhoest lineage.

In this paper, we describe the results of a qualitative and quantitative study of chromosomal reorganizations in X-irradiated (1 Gy and 2 Gy) lymphocytes from Macaca fascicularis (MFA) and Erythrocebus patas (EPA). A total of 515 breakpoints in M. fascicularis and 271 breakpoints in E. patas have been detected, identified and localized in the ideogram of the species. The Chi square test indicates that the distribution of breakpoints along the chromosomes is not random in M. fascicularis, and is not random for the p and q arms and bands in both species. Chromosome 5 of M. fascicularis (MFA5), chromosome 1 of E. patas (EPA1), and chromosome arms MFA5q, and EPA 1p are significantly more affected than expected, while chromosome MFA9 is less affected. Terminal regions of chromosome arms accumulate a higher number of breakpoints than the rest of the chromosome (44.4% in M. fascicularis and 45.98% in E. patas); 92.06% and 91.97% of breakpoints are observed in G negative bands in M. fascicularis and E. patas, respectively.

This paper presents the results of a study on the introduced, free-ranging patas monkey population of Southwestern Puerto Rico (SWPR). It describes information on the population size, social group composition, diet, daily ranging patterns, and patas home range during a 3 year period. The patas monkey population in the study area consisted of approximately 120 individuals in four heterosexual groups and several all-male bands. Within their home ranges (26.8 km2), the population density was 4.47 individuals/km2. Home range size among the population's four heterosexual groups varied from 3.72 km2 to 15.39 km2, and minimum daily distance traveled ranged from 0.8-2.0 km. In general, the social structure and mating system of this population parallels what has been described for African populations. However, habitat use, ranging behavior, and the quality of intergroup interactions suggests that patas of this population exhibit territorial behavior.

A 17 month field study of unprovisioned patas monkeys (Erythrocebus patas pyrrhonotus) in Laikipia, Kenya, using both ad libitum and scan sampling techniques, revealed that the diet of patas monkeys consists primarily of gum of Acacia drepanolobium, arthropods (both free-living and concentrated in the swollen thorns of A. drepanolobium), and other animals. This type of diet is normally found only in smaller-bodied primates. Results from vegetational transects suggest that the larger-bodied patas monkey can subsist on such a diet because gum and arthropods are relatively easily found in their habitat, thereby minimizing search time. Patas monkeys also spend more time moving and less time feeding (while not moving) than other Old World primates. The characteristic long limbs of patas may have evolved in response to feeding on small, nonusurpable, and widely distributed foods, in which access to foods is maximized while time and energy spent in terrestrial travel between food sites are minimized.

SV40 DNA has been found associated with several types of human tumors. We now report a sequence comparison of SV40 DNAs from pediatric brain tumors and from osteosarcomas with viral isolates from monkeys and from humans. We analyzed the entire genomic sequences of five isolates, Baylor and VA45-54 strains from monkeys and SVCPC, SVMEN, and SVPML-1 recovered from humans, and compared them to the reference virus SV40-776. The viral sequences were highly conserved, but isolates could be distinguished by variations in the structure of the viral regulatory region and in the nucleotide sequence of the variable domain at the C-terminus of the large T-antigen gene. We conclude that multiple strains of SV40 exist that can be identified on the basis of sequences in these regions of the viral genome. The isolates were more similar to each other and to the Baylor strain than to the reference strain SV40-776. Human isolates SVCPC and SVMEN were found to be identical. The DNAs present in some human brain and bone tumors were authentic SV40 sequences. Many of the C-terminal T-ag sequences associated with human tumors were unique, but some sequences were shared by independent sources. There was no compelling evidence for human-specific strains of SV40 or for tumor type-specific associations, suggesting that SV40 has a relatively broad host range. The source of the viral DNA found in human tumors remains unknown.

Homo erectus is notable for its taller stature and longer lower limbs relative to earlier hominids, but the selective pressures favoring such long limbs are unclear. Among anthropoid primates, patas monkeys (Erythrocebus patas) and extant hominids share several extreme characteristics involved with foraging and movement, including the relatively longest lower limb proportions, longest daily travel distances and largest home ranges for their body or group size, occupancy of some of the driest habitats, and very efficient thermoregulatory systems. We suggest that patas monkeys are an appropriate behavioral model with which to speculate on the selective pressures that might have operated on H. erectus to increase lower limb length. Here, in a comparison of the locomotor activities of patas monkeys and sympatric, closely related vervet monkeys (Cercopithecus aethiops), we provide evidence for the hypothesis that patas use their long stride more to increase foraging efficiency while walking than to run, either from predators or otherwise.

Preference for terrestrial substrates is one of the most significant adaptive differences between some members of the radiation of Old World higher primates and the anthropoids of the Neotropics (Le Gros Clark, 1959; Napier and Napier, 1967, 1985; Fleagle, 1988; Martin, 1990). Adaptations for terrestriality are most conspicuous among savanna baboons (Papio — Rose, 1977), geladas (Theropithecus — Jolly, 1967; Dunbar and Dunbar, 1974), and humans (Napier, 1967). Varying degrees of semi-terrestriality and terrestriality are also present among the African great apes (Gorilla — Remis, 1995 and Pan — Hunt, 1992; Doran, 1993) and some of the Asian colobines (Presbytis entellus — Ripley, 1967 and Rhinopithecus roxellana — Davison, 1982), guenons (Cercopithecus aethiops and Erythrocebus patas — Hall, 1965), mandrills and drills (Mandrillus — Jouventin, 1975), mangabeys (Cercocebus — Waser, 1984), and macaques (e.g., Macaca nemestrina — Caldicott, 1986). In contrast, terrestrial adaptations are notably absent from the otherwise diverse adaptive array of New World anthropoids.

Eight and a half years of dominace relations within a captive group of patas monkeys were analyzed. It was found that matrilineal kinship significantly influenced individuals' ranks. In contrast, with the exception of certain intramatiline changes, increasingage had no predictable effect on overall rank, at least for females (this was untestable for males). Offspring typically challenged maternal dominance and in eight or twelve dyads, offspring either fully rose over their mothers (three cases all daughters) or at least achieved dominance ambiguity with them. Additionally, two of the four younger sisters with an opportunity to rise in rank over an older sister did so. The group dominance hierarchy was unstable for 75% of the study due to a combination of agonistically induced and demographically induced rank changes. Concentration of the highest ranks in a single matriline showed a stronger association with group hierarchy stability than did the presence of an adult, nonatal male. Group hierarchy stability was associated with increased affiliation (sitting close and sitting touching), but otherwise there were no behavioral correlations. Individuals' ranks within the group hierarchy were unrelated to their chances of being wounded or having diarrhea. Adult females' ranks were over twice as stable as the group hierarchy (57.1% stability), but stability/instability was not correlated with any behavioral changes. Available evidence suggests tha dominance relations play only a minor role in the organization of patas monkeys' intragroup behavior.

A multiple schedule of repeated acquisition and performance of conditional discriminations was used to characterize the effects of two negative allosteric modulators of the gamma-aminobutyric acid (GABAA) receptor (ethyl beta-carboline-3-carboxylate [beta-CCE] and N-methyl-beta-carboline-3-carboxamide [FG-7142]), a hallucinogenic beta-carboline derivative (harmine), a benzodiazepine receptor antagonist (flumazenil) and a positive allosteric modulator (alprazolam). In the acquisition component, subjects acquired a different discrimination each session. Acquisition of a discrimination was defined by a decrease in errors as the session progressed. In the performance component, the discrimination was the same each session. Responding in both components was maintained by food presentation under a variable-ratio schedule. Incorrect responses in both components produced a 5-sec timeout. Alprazolam (0.1-18 mg/kg), beta-CCE (0.01-0.32 mg/kg), FG-7142 (0.1-18 mg/kg) and harmine (0.1-1.8 mg/kg) all dose-dependently decreased response rate in both components. However, accuracy of responding-was differentially affected by the drugs. Alprazolam selectively and dose-dependently increased percent errors in acquisition, whereas beta-CCE increased acquisition errors only at the highest doses tested in each subject. In contrast, FG-7142 and harmine had no effects on percent errors at doses that virtually eliminated responding. In all cases, performance accuracy was generally not affected. Flumazenil, at doses that had little or no effect (0.1 and 0.32 mg/kg) or occasionally decreased response rates (1 mg/kg) when administered alone, dose-dependently antagonized the rate-decreasing and error-increasing effects of beta-CCE, FG-7142 and alprazolam. In contrast, flumazenil failed to antagonize the effects of harmine. Thus, the negative allosteric modulators only moderately disrupted acquisition in comparison with the positive allosteric modulator, but the effects of both types of modulator were antagonized by the benzodiazepine antagonist flumazenil.

A previous attempt to model transplacental cisplatin exposure and genotoxicity employed several pregnant Erythrocebus patas monkeys; most of the animals were exposed near the end of gestation and cisplatin-DNA adduct analyses included only genomic DNA. Here, both genomic and mitochondrial DNA adduct formation have been determined in fetuses from two pregnant monkeys exposed at the end of the second trimester of gestation. Multiple fetal tissues were obtained after doses of 0.315 mg cisplatin/kg body weight (5.3 mg/m2 total) on days 101 and 106 of gestation. Cesarean sections were performed 24 h after exposure and 27 d after exposure. Cisplatin genomic (g)-DNA adducts were observed in fetal adrenal, brain, heart, kidney, liver, skin, spleen, and thymus. When placentas from the two animals were divided into four concentric regions at increasing distances from the umbilical cord, and g-DNA was assayed, cisplatin DNA adduct levels were similar in all four regions. Mitochondrial (mt)-DNA adducts were higher than g-DNA adducts in maternal liver and fetal liver, brain and kidney, suggesting that the mitochondria may constitute a particular target for cisplatin genotoxicity. The study demonstrates significant fetal genotoxicity in g-DNA and mt-DNA of patas monkeys exposed to cisplatin in utero, suggesting that similarly exposed human fetuses may also sustain drug-induced DNA damage.

DNA adducts are covalent complexes formed between genotoxic carcinogens and DNA bases, and constitute a critical early intermediate on the pathway of chemical carcinogenesis. Their accumulation in different tissues reflects the amount of activated carcinogen reaching DNA, and can therefore serve as an index of the biologically relevant dose reaching the target tissues or cells. Methylating agents are of interest in view of their occurrence in the environment and their use as cytotoxic drugs in cancer chemotherapy. Current evidence indicates that O6-methylguanine plays a particularly important role in the mutagenic, carcinogenic, and cytotoxic activities of methylating agents. O6-Methylguanine is repaired efficiently by the enzyme O6-alkylguanine-DNA alkyltransferase (AGT). Lack of this enzyme results in excessive accumulation of O6-methylguanine and recent evidence suggests that significant quantitative effects on adduct accumulation may be linked to conditions of very low AGT levels. This would be important from the point of view of clinical practice, since modulation of AGT is under investigation as a means of enhancing the therapeutic efficacy of clinical agents acting via the production of O6-methylguanine and related adducts, such as, for example, procarbazine, dacarbazine, and some nitrosoureas. The measurement of O6-methylguanine in human DNA has been employed as a tool to investigate the role of environmental methylating agents in human carcinogenesis. While the nature and origin of the methylating agents responsible for these adducts is currently unknown, recent studies in patas monkeys have shown that N-nitrosodimethylamine, a methylating carcinogen to which human exposure is well documented, is capable of efficiently generating O6-methylguanine in most tissues, including fetal tissues. Furthermore, it has been found that this damage is substantially enhanced by the coadministration of ethyl alcohol which acts by inhibiting the liver first-pass metabolism of the carcinogen, an observation which supports the hypothesis that alcohol consumption may act as a risk factor in human carcinogenesis by augmenting the action of nitrosamines.

N-nitrosodimethylamine (NDMA) is a human cancer initiator suspect. Ethanol, a cancer risk factor, may synergize with nitrosamines by suppressing hepatic clearance, to increase internal exposure. A limitation to these hypotheses is lack of activation of NDMA by many rodent tissues. However, systemtic primate studies are lacking. Patas monkeys were utilized to investigate NDMA activation by primate tissues in vivo, generating the promutagenic DNA lesion 0(6)-methylguanine (0(6)-meG). Adult monkeys received 0. 1 mg/kg NDMA by gavage, in some cases preceded by ethanol. Four hours after NDMA only, 0(6)-meG was detected in DNA from all tissues. Levels were highest in gastric mucosa and liver and were only about 50% lower in DNA from white blood cells, esophagus, ovary, pancreas, urinary bladder and uterus. With ethanol co-exposure, amounts of 0(6)-meG increased at least 2-fold in all tissues except liver. The largest effect was in esophagus (17-fold increase), followed by ovary, large intestine, urinary bladder, spleen and cerebellum (9- to 13-fold increases), and uterus, cerebrum and brain stem (7- to 8-fold increases). Alkylguanine alkyltransferase activities varied over a 30-fold range and were highest in liver and stomach. Thus primate tissues, especially those of the gastrointestinal and urogenital organs, are sensitive targets for DNA adduct damage due to NDMA, and ethanol co-exposure leads to striking increases in adducts. Our data support epidemiology implicating nitrosamines in causation of cancers of stomach and other organs, and alcohol as enhancing internal exposure to nitrosamines.

The erector spinae muscles of the patas monkey, hamadryas baboon, and spider monkey were dissected and the origins and insertions were described in detail. In the two terrestrial monkeys, a well-developed thoracolumbar segment of the muscle was observed. This trait seems to correlate to the sagittal movement of this region required in the pronograde quadrupedal locomotion. On the other hand, the erector spinae muscle of the spider monkey is quantitatively not so well developed and the arrangement of the muscle bundles was simpler than in the terrestrial monkeys. The arboreal habit of the spider monkey seems not to demand powerful extension in the thoracolumbar junction, and spinal rotation seems to be more important.

Socio-ethological studies on troops of African green monkeys (AGMs) (#Cercopithecus aethiops sabaeus$) and patas monkeys (#Erythrocebus patas$) in Senegal have documented physical contacts between these two species. Elevated simian immunodeficiency virus (SIV) seroprevalence rates have been reported for the different AGM subspecies. We report here the extent to which patas monkeys are infected and compare the relatedness of the viruses isolated from these two different species. Among the 85 AGMs and 54 patas monkeys studied, 47% and 7.5%, respectively, had antibodies that cross-reacted with HIV-2 envelope proteins. From two AGMs a virus was isolated. From the patas monkeys, virus isolation was generally not possible, but from one animal that was ill a virus designated pamG31 was amplified by PCR. In addition, for the two SIVagm isolates, an 830 bm region spanning the env and nef genes was amplified and sequenced. Comparisons of sequences from the env/nef region revealed 80% identity between pamG31 and SIVagm isolates from AGMs of the #sabaeus$ subspecies, and 94% identity between the two SIVagm isolates. Phylogenetic analysis showed that pamG31 belongs to the SIVagm #sabaeus$ subgroup. This is the first report of a lentiviral infection in a patas monkey. The close genetic relatedness between pamG31 and SIVagm #sabaeus$ viruses is a strong argument in favour of cross-species transmission of SIV between AGMs and patas monkeys in the wild. For these reasons, we propose to refer to this patas virus as SIVagm-pamG31. (Résumé d'auteur)

Perinatal nitrosamine exposures may contribute to childhood cancer risk. To test primate fetal susceptibility to formation of cancer initiation-related DNA adducts from nitrosamines, pregnant patas monkeys were given 1.0 or 0.1 mg/kg N-nitrosodimethylamine. Appreciable levels of the promutagenic O6-methylguanine adduct occurred in placental and fetal liver DNA after both doses and were lower but detectable in other fetal tissues after the higher dose. Coadministered ethanol (1.6 g/kg) reduced adducts in placenta and fetal liver by one-half and increased levels in other fetal tissues to the same degree. Thus, primate placenta and fetal tissues have a significant, ethanol-modulated capacity to activate N-nitrosodimethylamine, supporting implication of nitrosamines in human perinatal carcinogenesis and of alcohol as a modulating factor.

We report here on the ability of IDRA 21 and aniracetam, two negative allosteric modulators of glutamate-induced DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor desensitization, to attenuate alprazolam-induced learning deficit in patas monkeys working in a complex behavioral task. In one component of a multiple schedule (repeated acquisition or "learning"), patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four discriminative stimuli (geometric forms or numerals). In the other component (performance) the four-response chain was the same each session. The response chain in each component was maintained by food presentation under a fixed-ratio schedule. When alprazolam (0.1 or 0.32 mg/kg p.o.) was administered alone, this full allosteric modulator of gamma-aminobutyric acid type A (GABAA) receptors produced large decreases in the response rate and accuracy in the learning component of the task. IDRA 21 (3 or 5.6 mg/kg p.o.) and aniracetam (30 mg/kg p.o.) administered 60 min before alprazolam, having no effect when given alone, antagonized the large disruptive effects of alprazolam on learning. From dose-response studies, it can be estimated that IDRA 21 is approximately 10-fold more potent than aniracetam in antagonizing alprazolam-induced learning deficit. We conclude that IDRA 21, a chemically unrelated pharmacological congener of aniracetam, improves learning deficit induced in patas monkeys by the increase of GABAergic tone elicited by alprazolam. Very likely IDRA 21 exerts its behavioral effects by antagonizing AMPA receptor desensitization.

The promutagenic and procarcinogenic heterocyclic amines (HAs) found in cooked meats are N-hydroxylated by microsomal cytochrome P450 enzymes as the first step in their metabolic activation. In cynomolgus monkeys, one of the HAs, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), has been shown to be a potent hepatocarcinogen. However, the structurally similar HA 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) lacks this potency to induce hepatocellular carcinoma in monkeys. Liver microsomes from cynomolgus monkeys show a striking substrate specificity for the metabolic activation of IQ and MeIQx, the former being a far better substrate for N-hydroxylation. Western blot analysis showed that cynomolgus monkey hepatic microsomes constitutively express P450s immunologically related to the human CYP3A, CYP2C, and low levels of CYP1A1. For comparison, Western blot analysis of rat, human and patas monkey microsomes was also carried out. Treatment of cynomolgus monkeys with rifampicin induced hepatic cytochromes P450 related to human CYP3A4 and CYP2C9/10 without inducing CYP1A1 or CYP1A2. Immunoblot analysis also showed that chronic exposure of cynomolgus monkeys to IQ induced hepatic microsomal cytochrome CYP1A1 and CYP1A2, similarly but lesser in magnitude to that observed with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCCD) induction. Using the Ames Salmonella mutagenicity assay, we examined the effect of the inducers on the mutagenic activation (i.e. N-hydroxylation) of IQ and MeIQx by cynomolgus monkey hepatic microsomes. We also examined the mutagenic activation of these HAs by rat, human and patas monkey liver microsomes. Microsomes from cynomolgus monkeys treated with rifampicin showed a 3-fold increase in the mutagenic activation of IQ but showed no increase in the mutagenic activation of MeIQx. Since cytochromes P4503A and/or P4502C are constitutively expressed in cynomolgus monkey hepatic microsomes, and upon induction with rifampicin are associated with an increased metabolic activation of IQ but not MeIQx, it appears that CYP3A and/or CYP2C are the isoform(s) showing the selective substrate specificity in the metabolic activation of IQ over MeIQx. Treatment of monkeys with TCDD significantly increased the mutagenic activation of both IQ and MeIQx, concomitant with an induction of CYP1A isozymes. Thus, it appears that TCDD-inducible CYP1A enzymes N-hydroxylate both substrates without selectivity. Together, these findings suggest that CYP3A and CYP2C are the principal isoforms in the cynomolgus monkey, associated with the metabolic activation implicated in the induction of hepatocarcinogenicity by IQ. Furthermore, the poor metabolic activation of MeIQx by CYP3A and CYP2C, coupled with low constitutive levels of CYP1A isozymes, provide a metabolic explanation for the low hepatocarcinogenic potency of MeIQx in cynomolgus monkeys.

The capacity of a recombinant glutathione S-transferase from Schistosoma mansoni (rSm28GST) to vaccinate primates (Erythrocebus patas) against a heterologous infection with Schistosoma haematobium has been tested. Two injections of the purified molecule with Muramyl-Di-Peptide (MDP) as adjuvant resulted in a high level antibody response in the five immunized animals and in a significant reduction in worm fecundity compared to the controls which received adjuvant alone. Mean levels of daily egg excretion in urine an faeces were reduced by respectively 55% and 74% although perfusion revealed that worm burdens were similar in both groups. The protective effect was long lasting since it was maintained up to the end of the experiment, 42 weeks after infection. Hatching rates and the numbers of intra-uterine eggs were also significantly affected by the vaccination. Tissue eggs were also drastically diminished in the urogenital system (-80%) but the reduction was not statistically significant. One animal was not protected by the immunization. There was a good correlation between parasitological data and the intensity of bladder lesions assessed by microscopic examination. Polypoid formations together with an intense exudation of the lamina propria were frequently seen in the controls but rarely in the vaccinated group where formation of scar tissue was predominant. These results underline the vaccine potential of the recombinant Sm28GST as a possible valuable prophylactic tool for the control of egg-induced pathology and transmission of African schistosomes.

Imidazenil is a highly potent partial allosteric modulator of gamma-aminobutyric acid action at a great variety of gamma-aminobutyric acid(A) receptors, whereas alprazolam is a full allosteric modulator at these receptors. Data in rats indicate that imidazenil, like alprazolam, has pharmacological effects in animals indicative of anxiolytic, antipanic and anticonvulsant activity in humans, but unlike alprazolam, in animals imidazenil does not produce ataxia, sedation, tolerance or dependence nor does it potentiate the effects of ethanol. To extend the study of the imidazenil pharmacological profile, we administered this drug and alprazolam, alone and in combination, in monkeys working in a complex behavioral task. In one component of a multiple schedule (repeated acquisition or "learning"), patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four discriminative stimuli (geometric forms or numerals). In the other component (performance), the four-response chain was the same each session. The response chain in each component was maintained by food presentation under a fixed-ratio schedule. When alprazolam (0.01-0.32 mg/kg, p.o.) was administered alone, the overall response rate in both learning and performance decreased and the percent errors in both components increased with increasing doses. Learning, however, was more sensitive than performance; i.e., error-increasing effects were seen in learning at doses that had no effect on performance accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

It was recently reported that toombak, a type of snuff used in the Sudan, contained unusually high levels of tobacco-specific nitrosamines. To estimate the internal dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) received by individuals who use this type of tobacco, urine from a group of users was analyzed for 2 metabolites of NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its O-glucuronide, NNAL-Gluc. NNK is a strong lung carcinogen believed to contribute to human lung cancer. NNAL is also a lung carcinogen. NNAL and NNAL-Gluc were analyzed by gas chromatography with a nitrosamine selective detector. The average levels detected were 0.39 +/- 0.14 (SD) nmol/ml urine (n = 7) and 0.88 +/- 0.50 nmol/ml urine (n = 7), respectively. In a 24-h period, these individuals would excrete from 0.12 to 0.44 mg of these two metabolites (expressed per mg NNAL). Therefore, assuming chronic toombak use, the minimum daily dose of NNK to which these users were exposed was 0.12-0.44 mg. This is the highest documented uptake of a nonoccupational carcinogen. Two diastereomers of NNAL-Gluc were present in all urine samples analyzed. Previously, these two diastereomers were identified in the urine of an NNK-treated patas monkey but only one was detected in the urine of NNK-treated rats. The level of the 4-hydroxy-1-(3-pyridyl)-1-butanone releasing hemoglobin adduct was also quantified in these individuals. This adduct is believed to be a measure of NNK activation. The levels ranged from 68 to 323 fmol/g hemoglobin [mean, 148 +/- 104 (SD)]. The wide range of adduct levels which were observed suggests that despite similar levels of NNK exposure, there are significant differences in the ability of individuals in this population to activate NNK, as well as potential differences in their cancer risk.

This article describes a new synthetic material for grafting periodontal osseous defects. Compared to grafts of similar-sized hydroxyapatite, tricalcium phosphate, and unimplanted controls, PerioGlas achieved histologically superior repair of surgically created defects in the monkey model. Superior repair was noted when evaluating for new bone and the degree of cementum regeneration. Epithelial downgrowth appeared to be retarded in the PerioGlas sites and not in the other materials. When comparing clinical handling characteristics, PerioGlas was found to have excellent packing and manipulative features that were preferred by the operators to the other materials. The property of epithelial downgrowth inhibition may be significant in the superior regenerative property of PerioGlas.

Erythrocebus patas (Schreber, 1775). Die Säugethiere, 1:98. TYPE LOCALITY: Senegal. DISTRIBUTION: Savannahs, from W Africa to Ethiopia, Kenya, and Tanzania. STATUS: CITES - Appendix II. SYNONYMS: albigenus, albosignatus, baumstarki, circumcinctus, formosus, kerstingi, langheldi, poliomystax, poliophaeus, pyrrhonotus, rubra, rufa, sannio, whitei, zechi., Published as part of Colin P. Groves, 1993, Order Primates, pp. 243-277 in Mammal Species of the World (2 nd Edition), Washington and London :Smithsonian Institution Press on page 265, DOI: 10.5281/zenodo.7353122

A human cDNA, UDPGTh-3, encoding a dihydrotestosterone/5 alpha-androstane-3 alpha,17 beta-diol UDP- glucuronosyltransferase (transferase) has been isolated and characterized. The nucleotide sequence of UDPGTh-3 encodes a 530 amino acid protein with a typical membrane insertion-signal peptide, a membrane-anchoring domain, and three potential asparagine-linked glycosylation sites. Alignment shows that this encoded isozyme is 96% identical to an apparent estriol-metabolizing isoform, HLUG4 [Coffman, B. L., et al., (1990) Arch. Biochem. Biophys. 281, 170-175]. The udpgth-3 isozyme is 78% identical to two other steroid isoforms, HLUG25 (udpgth-1) [Jackson, M. R., et al. (1987) Biochem. J. 242, 581-588; Ritter, J. K., et. al. (1992) Biochemistry 31, 3409-3414] and udpgth-2 [Ritter, J. K., et al. (1990) J. Biol. Chem. 265, 7900-7906]. udpgth-2 and udpgth-1 metabolized parallel substrates (stereospecific estriols, 3,4-catechol estrogens, and the bile salt hyodeoxycholate), except that udpgth-2 was 100-fold more effective than udpgth-1. The mRNA encoding udpgth-3 is 2.4 kb in size and is present in liver, prostate, and testis; the mRNA encoding udpgth-2 is located in liver and kidney, whereas that for udpgth-1 is liver-specific. Each of the liver mRNA species encoding udpgth-3, udpgth-2, or udpgth-1 was induced 2.5-3-fold by phenobarbital treatment of the Erythrocebus patas monkey. In 16 human liver mRNA samples, the message encoding udpgth-3 was generally uniformly expressed and that for udpgth-1 exhibited wide variations in its level, whereas that for udpgth-2 was barely detectable in nine samples and not detectable in the others. Three samples contained no message for either isoform. Substrate turnover by udpgth-3 is ranked as follows: phenolphthalein > 5 alpha-androstane-3 alpha,17 beta-diol > 5 alpha- dihydrotestosterone = 4-hydroxybiphenyl > phenolsulfonphthalein (phenol red) > phenolphthalin. Genes encoding udpgth-3, udpgth-2, and udpgth-1 mapped to human chromosome 4 with genomic DNA from human/mouse and human/hamster somatic cell hybrids; the genes encoding udpgth-1 and udpgth-2 mapped specifically to band 4q28. udpgth-3 exhibited similar Km values both for 5 alpha-dihydrotestosterone (10 microM) and for its metabolite, 5 alpha-androstane-3 alpha,-17 beta-diol (12.5 microM).(ABSTRACT TRUNCATED AT 400 WORDS)

In humans, relatively little is known on the association of prenatal exposure to cancer-causing agents and the development of specific tumors later in life as a consequence. Therefore, the effects on the offspring of carcinogen exposure during gestation and the development of tumors later in life were studied in nonhuman primates.Pregnancy was confirmed in Erythrocebus patas (patas) and Macaca mulatta (rhesus) by palpation at 27 to 40 days of gestation. Pregnant animals were treated once weekly intravenously from that time with N-nitrosoethylurea according to different dosing regimens for 6 to 19 weeks with 0.05 to 0.2 mmol/kg/injection.A common lesion developing in only the offspring of mothers treated early in pregnancy was identical with the human condition referred to as intramuscular angioma, hemangioma, or infiltrating angiolipoma of skeletal muscle. In the rhesus, one of 7 animals, and in the patas, 18 of 78 monkeys developed these processes (10 to 40% per group). The lesions typically arose within, infiltrated and displaced skeletal muscle. They occurred most commonly in the lower extremities, followed by the upper extremities and the head; they recurred in three cases of incomplete resection but did not metastasize. The tumors were seen mainly in young adults of both sexes (latency range: 4 to 76 months) and consisted of vessels of variable caliber, and to varying degrees, mature adipose and connective tissue, undifferentiated mesenchymal cells, and lymphoid cell aggregates. Ultrastructurally, the endothelium possessed numerous Weibel-Palade bodies and showed strong immunoreactivity for von Willebrand factor by immunohistochemistry and immunoelectron microscopy.The present investigation suggests a classification of these lesions as infiltrating angiolipoma of skeletal muscle originating from a pluripotent mesenchymal stem cell, caused by exposure to carcinogens during early pregnancy. The great clinical and morphologic similarity of this condition with that observed in humans suggests that it may likewise be caused by exposure to an agent during pregnancy.

Twenty-five of 30 patas monkeys (Erythrocebus patas) inoculated with varying numbers (35 to 135) of third-stage larvae of Mansonella ozzardi developed patent infections in an average of 163 days. There was no correlation between the size of the inoculum and the length of the prepatent period. Ten of the monkeys were monitored thereafter by regular blood examination for extended periods of time in order to characterize the onset, course and duration of patency. Typically, with the onset of patency, microfilaremias increased steadily, peaking at about 20 weeks and then decreased slowly stabilizing at low levels for up to 48 weeks. Thereafter microfilariae disappeared from the blood and occasionally reappeared in scanty numbers. Laparotomies and followup studies indicated that the spleen was involved in the suppression of peripheral microfilaremia as had been observed earlier in patas monkeys infected with Loa loa. In ten monkeys splenectomized after the initial "wave" of microfilaremia, it was observed that (a) 30% of the animals remained amicrofilaremic, (b) another 30% reestablished patent infections but microfilaremias were lower than presplenectomy levels, and (c) in the remaining 40%, levels of microfilaremia equaled or exceeded pre-splenectomy levels. Patent infections persisted for up to 212 weeks. One monkey splenectomized prior to inoculation with 87 larvae developed a patent infection with microfilaremia which persisted for 156 weeks. Three monkeys with low and high levels of microfilaremia bled at four hour intervals over a 28 hour period showed no evidence of periodicity in the microfilaria.(ABSTRACT TRUNCATED AT 250 WORDS)

Les observations preliminaires de singes patas en captivite ne revelent aucune evidence de changement significatif quant aux comportements sociaux ou agonistiques, (a) tout au long du cycle menstruel, (b) plus specifiquement pendant la phase initiale premenstruelle/menstruelle. Malgre une mention de comportements apparentes au PMS (syndrome pre-menstruel) chez les babouins sauvages, il n'existe jusqu'a present aucune preuve suffisante pour justifier l'extension du label PMS aux primates non-humains

To study the interaction between the primate lentiviruses simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) and the CD4 receptor we have cloned and sequenced the CD4 molecule from six non-human primate species: African green monkeys (three subspecies: sabeus, pytherethrus, aethiops), sooty mangabeys, patas monkeys, chimpanzees, rhesus macaques, and pig-tail macaques. Molecular cDNA clones representing CD4 mRNA were generated from total RNA from peripheral blood mononuclear cells (PBMC) by polymerase chain reaction (PCR) amplification including reverse transcriptase in initial reactions followed by two rounds of nested amplifications. Primer sequences were selected from regions conserved among human and rodent CD4 genes. Alignments of deduced amino acid sequences revealed interesting findings. First, all of the primate CD4 molecules were about 90% identical to the human CD4 sequence except the chimpanzee (98%). Second, two macaques or two African green monkey subspecies were as distanly related as the human versus chimpanzee sequences. Third, relatedness of CD4 sequences could not be predicted on the basis of geographic origin (Asian vs. African). Finally, upon sequencing several clones from individual monkeys, a low degree of sequence variation (nucleotide substitutions, deletions, and insertions) was found within the same animal, and in case of sooty mangabeys two distict populations of CD4 molecules were present within three of four individuals. The distinguishing features involved eight amino acid changes, including a single lysine deletion relative to a primate consensus sequence in the first complementary-determing region of V1J1. These two CD4 populations were present also at the genomic DNA level and may arrive from the two chromosomal alleles, suggesting the existence of distinct sooty mangabey subspecies. Overall, the V1J1 and to a lesser extent V2J2 were the most variable regions among the sequences examined. By construction and expression in mammalian cell lines of CD4 chimeras in which these regions of the human CD4 were replaced by those of the African green monkey and pig-tail macaques, a higher molecular mass of the CD4 chimeras were obtained in sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggesting that the additional N-linked glycosylation sites present in these monkey CD4 are also used.

Male and female patas (Erythrocebus patas) and cynomolgus (Macaca fascicularis) monkeys were treated with phenobarbitone (PB) and examined for the induction of various cytochrome P450 (P450)-mediated drug metabolizing enzymes. Hydroxylation of testosterone at the 6 beta, 2 beta, and 15 beta positions, metabolites normally associated with CYP3A P450s increased 2- to 5-fold in PB-treated animals. Induction of this P450 family was confirmed by the use of polyclonal antisera directed against the human CYP3A enzymes which inhibited both induced and constitutive 6 beta- and 15 beta-hydroxylase activities in both species of monkeys. The enzymatic activities testosterone 16 beta-hydroxylation, pentoxyresorufin O-dealkylation [PROD], and benzyloxyresorufin O-dealkylation [BZROD] typically associated with the rodent CYP2B subfamily in rodents were also examined. Testosterone 16 beta-hydroxylation activity was highly induced up to 15-fold in both species of monkeys to maximal levels similar to those induced in PB-treated male rats. BZROD was similarly induced up to 10-fold in both species of monkeys, but the maximal levels of BZROD achieved were substantially lower than those obtained in PB-treated rats. Finally, PROD yielded an idiosyncratic response showing substantial induction (> 30-fold) in certain patas monkeys (4 out of 8) but minimal (< 5-fold) induction in the other patas monkeys (4 out of 8) or any of the cynomolgus monkeys (0 out of 8). Immunodetection of various cytochromes using polyclonal antisera directed against rat cytochromes confirmed the induction of CYP3A proteins as well as the induction of protein(s) immunologically cross-reactive with rat CYP2B P450s. BZROD, PROD, or testosterone 16 beta-hydroxylase activities, were not inhibited by antibody to CYP3A P450s. However, high concentrations of polyclonal antiserum directed against rat CYP2B inhibited all three activities in PB-induced patas monkeys. In contrast, this antiserum failed to inhibit the hydroxylation of testosterone at the 6 beta or 2 beta positions. Induction of the CYP2C subfamily was observed by immunochemical detection. Interestingly, induction of this subfamily appeared to be more pronounced in cynomolgus than in patas monkeys. Finally, we failed to observe significant sex-dependent differences in P450-mediated enzymatic activities in either control or induced monkeys. These results confirm the induction of a similar spectrum of P450 proteins by PB in non-human primates to that which has previously been observed in rodents.

An epizootic attributable to Yersinia pseudotuberculosis infection was confirmed in captive ruminants in a wildlife park by microbiologic and histologic findings. An epornitic of Y pseudotuberculosis infection was identified at the same period in a vicinity near the ruminant deaths. Yersinia pseudotuberculosis can infect human beings and cause acute enteritis and mesenteric lymphadenitis. People in contact with infected animals should use extreme caution and use good sanitary precautions to preclude transmission of this agent.

Four bioactive ceramic materials currently recommended for regeneration of osseous tissues in treatment of periodontal disease have been compared with Bioglass particulates, of equivalent size in two compositions, in a monkey model. Both Bioglass materials were found to be easily manipulated, were haemostatic and osteoproductive allowing restoration of both alveolar bone and periodontal ligament. Epithelial downgrowth was inhibited and epithelial attachment was close to the preimplantation level. The other materials were slower to act and epithelial downgrowth was to the same level as in unfilled control defects.

Simian varicella virus (SVV) causes a varicella-like disease in non-human primates. In this study, SVV virions were purified from SVV-infected BSC-1 cells by zonal and differential gradient centrifugation and the virion polypeptide composition was analysed by SDS-PAGE. SVV virions had a buoyant density of 1.21 g/ml, identical to the value obtained for varicella-zoster virus (VZV) virions purified by the same method. Electron microscopy of the concentrated SVV virions revealed characteristic herpesvirus morphology. SVV virions consisted of at least 30 polypeptide species ranging from 16K to greater than 200K. The electrophoretic profiles of radiolabelled SVV and VZV virion polypeptides were very similar. Immunoprecipitations of solubilized SVV-infected cell preparations using SVV immune sera revealed at least 18 viral polypeptides with an Mr range of 12K to 142K and six glycoproteins ranging from 46K to 115K. In addition, extensive cross-reactivity between SVV and VZV proteins and glycoproteins was demonstrated by immunoprecipitation with heterologous immune sera. The high degree of antigenic relatedness between SVV and VZV provides further support for simian varicella as a model for VZV infections.

The southern patas monkey Erythrocebus patas baumstarki is a subspecies thought to be endemic to central north Tanzania but its distribution and abundance is not well documented. We therefore review what is known about the historical and current distribution of the south- ern patas. It appears that, at present, the southern patas occurs in three populations, in the Serengeti, Mt Kiliman- jaro and Arusha. Since 1995 the gaps among these three populations have become larger, thereby increasing their isolation. The available data suggest that, at present, south- ern patas occur over c. 20,700 km 2 (c. 2.3% of Tanzania's land surface area). In 1995 this was c. 30,800 km 2 (c. 3.5% of the land surface area). As such, the geographical range of the southern patas has declined by c. 33% since 1995. There are unlikely to be . 900 southern patas today, and there could be , 150. Our recommendations are to (1) maintain an internet accessed database (PatasBase) into which sight- ings of the southern patas can be entered, (2) interview members of local communities to assess past and current distribution and abundance of the southern patas, (3) con- duct field studies to obtain more detailed information on the distribution, abundance, and conservation status of patas in Tanzania, (4) undertake ecological and behavioural re- search on selected groups of southern patas, and (5) prepare and implement a conservation action plan for the southern