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Natural regulation of rhesus monkey populations in Kathmandu, Nepal. Rhesus monkey groups near Kathmandu, Nepal, show demographic patterns of intrinsic population stability.

In Kathmandu valley, two populations of rhesus monkeys which are totally protected, have shown relatively stable numbers over a period of several years. Population stability within heterosexual troops appears to have been maintained through lower birth rates and slightly higher infant and adult mortality rates than in comparable rhesus populations in India which have been subject to trapping. Although the behavioral and physiological mechanisms by which these demographic changes occur are not known, behavioral observations on these populations suggest several possibilities. These data represent the first indication of possible mechanisms for population regulation in natural rhesus populations.

Animals↗

The neuroprotective effects of CGP 3466B in the best in vivo model of Parkinson's disease, the bilaterally MPTP-treated rhesus monkey.

The propargylamine CGP 3466B prevents dopamine cell death both in vitro and in rodent models of Parkinson's disease. The present study investigates the efficacy of this compound to prevent the behavioral consequences of dopaminergic cell death in the best animal model of Parkinson's disease, the bilaterally MPTP-treated monkey. Rhesus monkeys were bilaterally treated with MPTP, using a two-step procedure: 2.50 mg MPTP was infused into the left carotid artery followed by a second bolus of 1.25 mg into the right carotid artery, 8 weeks later. Subcutaneous injection of either 0.014 mg/kg CGP 3466B (n = 4) or its solvent (distilled water; n = 4), twice daily for fourteen days, started two hours after the second MPTP infusion. A Parkinson rating scale was assessed for the evaluation of the effects. After the first MPTP treatment, the monkeys developed mild to moderate parkinsonian symptoms. The second MPTP treatment strongly increased the severity of Parkinson scores in all control monkeys, as assessed on day 3, 7, 14, 21, 28 and 35 after the second MPTP treatment. In contrast, CGP 3466B nearly completely prevented the increase of parkinsonian symptoms after the second MPTP treatment. The therapeutic effects of CGP 3466B were still present after a washout period of 3 weeks, implying that the effects were not symptomatic. These data are the first to show that the systemic administration of CGP 3466B is able to prevent the development of MPTP-induced motor symptoms in primates. This compound may have great value for inhibiting the progression of the neurodegenerative process in patients with Parkinson's disease.

Animals↗

Comparative studies with six extenders for sperm cryopreservation in the cynomolgus monkey (Macaca fascicularis) and rhesus monkey (Macaca mulatta).

Ejaculated spermatozoa from cynomolgus monkeys and rhesus monkeys were frozen in straws with six different extenders (TTE, DM, mDM, LG-DM, G-DM, and TCG) containing glycerol. Sperm motility and head membrane and acrosomal integrity were evaluated after freezing and thawing, and the cryoprotective effects were compared among the extenders and the two species studied. The results showed that sperm motility and motility recovery with the six extenders were comparable for the cynomolgus and rhesus monkeys. There was no significant difference in sperm motility and head membrane integrity among the six extenders in either the cynomolgus or rhesus monkeys (P>0.05). However, a slightly but statistically lower percentage of acrosomal integrity was found with TCG in both species compared to the other extenders (P<0.05). These findings demonstrate that TTE, DM, mDM, LG-DM, G-DM, and TCG are equally suitable extenders for the cryopreservation of spermatozoa from cynomolgus and rhesus monkeys.

Acrosome↗

Conjugated and unconjugated bilirubins in bile of humans and rhesus monkeys. Structure of adult human and rhesus-monkey bilirubins compared with dog bilirubins.

1. Bilirubin-IXalpha, -IXalpha diglucuronide, -IXalpha monoglucuronide, -IXalpha monoglucoside -IXalpha monoxyloside, a bilirubin-IXalpha diconjugate containing glucose and another unknown compound, and bilirubin-IXbeta are present in gall-bladder bile of adult human, rhesus monkey and dog. Dog bile normally also contains other bilirubin-IXalpha diconjugates, i.e. compounds containing two conjugating sugars such as glucuronic acid and glucose, glucuronic acid and xylose and glucose xylose. 2. Azopigments alphaF, alphaO, alpha2, alpha3, betax and delta derived from human and rhesus-monkey bilirubins are identical in their chemical composition with those obtained from the dog. 3. Azopigments alphaF and betax found in diazotized biles of adult humans, rhesus monkeys and dogs are products of unconjugated bilirubin-IXbeta. 4. Technical modifications of previously published procedures [Heirwegh, Fevery, Michiels, Van Hees & Compernolle, (1975) Biochem. J. 145, 185-199] were introduced which make it possible to separate the bilirubins, diazotize the separated bilirubins, extract the azopigments and chromatograph them in one working day (6-8h).

Adult↗

Structure of rhesus monkey relaxin predicted by analysis of the single-copy rhesus monkey relaxin gene.

The gene encoding rhesus monkey relaxin has been investigated. A cDNA library was prepared using corpus luteal RNA from a pregnant rhesus monkey, cDNA clones encoding relaxin were isolated and the nucleotide sequence was determined. The amino acid sequence of rhesus monkey preprorelaxin, predicted from the cDNA, demonstrates that the sequence has not been strongly conserved when compared with that of man, although features characteristic of the relaxin molecule have been maintained. This structural information will allow production of rhesus monkey relaxin, leading to studies investigating the bioactivity of relaxin in a homologous primate system. Southern blot analysis indicated that there is only one relaxin gene in the rhesus monkey and baboon genomes. In this respect these primate genomes are different from the human genome which contains two relaxin genes.

Amino Acid Sequence↗

Use of human leukocyte-specific monoclonal antibodies for clinically immunophenotyping lymphocytes of rhesus monkeys.

The rhesus monkey (Macaca mulatta) is an important experimental animal frequently utilized for studies of infectious diseases, immunity, hematopoiesis, and transplantation. Since the structure of cell surface molecules is phylogenetically conserved, monoclonal antibodies raised against human leukocyte antigens can sometimes recognize the homologous determinant on monkey leukocytes. To facilitate better utilization of this animal model, we tested 89 commercially available monoclonal antibodies which define 27 human cell surface antigens for reactivity with rhesus monkey PBL. Certain antigens which delineate clinical useful lymphocyte subsets such as CD2, CD4, CD8, CD14, CD16, CD20, and MHC class II are apparently well conserved since most human cell-specific antibodies identified the homologous cell subset in monkeys. However, other antigens such as CD3, CD19, CD45, and CD56 were identified infrequently by human cell-specific antibodies. FITC-modification of antibodies which had no effect on their binding to human cells occasionally inhibited antibody binding to monkey cells. Nevertheless, an adequate number of cross-reactive monoclonal antibodies was identified to allow gating of lymphocytes for accurate flow cytometric analysis and quantitation of the major lymphocyte subsets of the rhesus monkey. The T lymphocyte subset distribution in blood and lymphoid tissue of rhesus monkeys was similar to man. However, the B subset was significantly larger in monkeys. The daily variation in absolute PBL subset size was marked and found to be due mainly to daily fluctuations in total lymphocyte number.

Animals↗

Capillary changes in hippocampal CA1 and CA3 areas of the aging rhesus monkey.

The rhesus monkey is considered a useful animal model for studying human aging, because non-human primates show many of the neurobiological alterations that have been reported in aging humans. Cognitive impairment that accompanies normal aging may, at least partially, originate from capillary changes in the hippocampus, known to be involved in learning and memory. Age-related effects on the cerebral capillaries in the non-human primate hippocampus have not yet been studied. Therefore, we investigated age-related microvascular changes in the hippocampus of the aged non-human primate. We examined by electron microscopy the microvascular ultrastructure in the CAI and CA3 areas of 14 male rhesus monkeys (Macaca mulatta), ranging from 1 to 31 years of age. The percentages of capillaries showing basement membrane thickening and deposits of collagen in the basement membrane were determined semiquantitatively in 4 young (1-6 years), 6 middle-aged (17-24 years), and 4 aged (29-31 years) monkeys. Aberrations in the basement membrane are few in young subjects (28 +/- 6% of capillaries), and occur with increasing frequency during the aging process in rhesus monkeys (aged animals: 71 +/- 5% of capillaries). This could be ascribed to an aging-associated increasing number of capillaries showing depositions of collagen fibrils, rather than local thickenings of the basement membrane. The observed changes in microvascular integrity are very similar to those seen in humans, supporting the view of rhesus monkeys as a model for human aging. The slow but steady progression of these changes could be detrimental for an efficient nutrient supply of the neuropil, and might therefore contribute to decreased cognitive functioning during normal aging.

Aging↗

The relationship between induced reciprocal translocations and cell killing of rhesus monkey spermatogonial stem cells after combined treatments with follicle-stimulating hormone and X-rays.

The induction of reciprocal translocations in spermatogonial stem cells of monkeys (rhesus and crab-eating), visualized in dividing primary spermatocytes, was studied after combined treatments with follicle-stimulating hormone (FSH, 54 IU/kg/week) and X-rays (1 Gy). No clear differences in the frequencies of induced translocations between FSH-pretreated and non-pretreated animals were recorded. Comparison of these translocation data with studies on cell killing in the same monkeys shows that the ratio between the probabilities that radiation-induced basic lesions kill a cell or produce translocations (the p/c ratio) is of the same order of magnitude as that observed for the mouse. Consequently the well documented differences in radiation response between the rhesus monkey and the mouse cannot be explained by differences in the p/c ratio. It is concluded that differences in multiplication-differentiation patterns of surviving stem-cell spermatogonia after irradiation are probably responsible for the observed differences between mice and rhesus monkeys.

Animals↗

Identification of the bZIP and Rta homologues in the genome of rhesus monkey rhadinovirus.

Rhesus monkey rhadinovirus (RRV) is a gamma2-herpesvirus identified from the peripheral blood mononuclear cells of rhesus macaques (Macaca mulatta). Serologic studies suggested that the infections of RRV are prevalent among rhesus monkeys. RRV can be efficiently propagated and grows to a high titer in cultured rhesus monkey fibroblasts, thus providing a valuable model to study the rhadinovirus replication. By comparative genomic studies, here we describe the identification of two potential transcriptional factors encoded by RRV, designated as R-Rta and R-bZIP. Initial functional characterization of these products suggested that R-Rta is a potent transcriptional activator and R-bZIP forms homodimers in vivo. Viral homologues of R-Rta and R-bZIP, previously identified from other rhadinoviruses, have been implicated in serving as molecular switches in lytic replication.

Amino Acid Sequence↗

Conjugated and unconjugated bilirubins in humans and rhesus monkeys. Structural identity of bilirubins from biles and meconiums of newborn humans and rhesus monkeys.

1. Bilirubin-IXalpha monoglucuronide was the predominant bilirubin in biles and meconiums of newborn humans and rhesus monkeys. Rhesus-monkey baby biles contained slightly more diglucuronide than did human baby biles. 2. Bilrubin-IXalpha glucoside, bilirubin-IXalpha xyloside and bilirubin-IXbeta were also constituents of human and rhesus-monkey baby biles and meconiums. Bilirubin-IXalpha glucuronide glucoside was present in human and rhesus-monkey baby biles but not in meconiums. The identity of the bilirubins was confirmed by u.v.-visible and mass spectroscopy of the azodipyrroles obtained by treating the bilirubins with diazotized ethyl anthranilate. The resulting azodipyrroles were identical with the corresponding azodipyrroles obtained from human adult biles and also from reduced isomers of biliverdin. 3. Bilirubin-IXbeta was present in much higher proportions in the extracts of meconiums than in the extracts of biles from the same babies. 4. Oxidation of bilirubins to biliverdins occurs in utero to a small but undetermined extent. The resulting green pigments were present in meconiums collected from the lower small and large intestines of newborn babies and rhesus monkeys. 5. Butanol extracted most of the bilirubins present in biles. This modified method proved to be quick and easy. Little hydrolysis of bilirubins took place during extraction or separation by t.l.c.

Adult↗

Effect of an LHRH agonist on pituitary and testicular function in rhesus monkeys.

Male rhesus monkeys were given 100 micrograms [(imBzl)-D-His6,Pro9-NEt]-LHRH (LHRH-A), a potent LHRH agonist, s.c. daily for 40 weeks. The first dose of LHRH-A caused acute increases (2-4 h after injection) in serum LH (50-fold), FSH (2 X 5-fold) and testosterone (15-fold) concentrations. Chronic treatment led to a 95% decrease in LH and FSH responses. In spite of a marked decrease in LH response the effect on testosterone response was less evident. Administration of 50 i.u. hCG to control and LHRH-A-treated animals showed that the testicular steroidogenic response was unimpaired by the chronic treatment. Evaluation of the electroejaculated semen at regular intervals showed that there was no consistent reduction in the sperm count of LHRH-A-treated monkeys. Testicular biopsies showed that normal spermatogenesis was occurring in all treated animals, but testicular volume was significantly decreased. These results suggest that, in rhesus monkeys, the pituitary is more susceptible to desensitization by chronic LHRH agonist treatment than are the testes, and that LHRH agonists do not have direct antitesticular effect in rhesus monkeys.

Animals↗

Discriminative stimulus effects of nalbuphine in rhesus monkeys.

Three rhesus monkeys discriminated between 0.178 mg/kg of nalbuphine and saline while responding under a fixed-ratio 5 schedule of stimulus-shock termination. Nalbuphine produced dose-related increases in drug-lever responding with > or = 90% of responses occurring on the drug lever at doses larger than 0.1 mg/kg. The duration of action of the discriminative stimulus effects of nalbuphine was less than 5.25 hr. Rank order potency of compounds that substituted for the nalbuphine discriminative stimulus (i.e., > or = 90% responding on the nalbuphine lever) in all three subjects was fentanyl > butorphanol > methadone > morphine. Compounds that did not substitute completely in all monkeys included the kappa agonists ethylketocyclazocine, enadoline, spiradoline and U-50,488 and the nonopioids cocaine, d-amphetamine, clonidine, ketamine and phencyclidine. Naltrexone antagonized the discriminative stimulus effects of nalbuphine, shifting the nalbuphine dose-effect curve in a manner that was consistent with mu receptor mediation. Results from the current study demonstrate that, in rhesus monkeys, the discriminative stimulus effects of nalbuphine are mediated by mu opioid receptors. Although there is evidence suggesting that nalbuphine has kappa agonist effects (e.g., subjective effects in humans), results from several studies, including the current study, strongly suggest that in rhesus monkeys nalbuphine does not exert agonist actions at kappa receptors. Moreover, these data indicate that differences in behavioral effects between nalbuphine and prototypic mu opioids (e.g., morphine) probably result from differences in activity (e.g., efficacy) at mu receptors rather than any kappa agonist actions of nalbuphine.

Analgesics, Opioid↗

Cholecystokinin-decreased food intake in rhesus monkeys.

Five rhesus monkeys were infused intravenously with partially purified cholecystokinin (CCK) Just prior to a test meal of solid food after overnight food deprivation; CCK produced large, rapid, dose related suppressions of feeding. The lowest dose tested (5 Ivy U/kg body wt) produced a significant inhibition of food intake (26% suppression, P less than 0.05). Equivalent infusions of partially purified CCK or the synthetic COOH-terminal octapeptide of CCK (a pure fragment with all the biological activity of the full molecule) produced equivalent suppressions. In a second experiment, gastric preloads of a potent releaser of endogenous CCK, L-phenylalanine (L-Phe), and a weak releaser, D-phenylalanine (D-Phe) were compared for their relative abilities to suppress food intake at a test meal in nine rhesus monkeys after overnight deprivation. L-Phenylalanine produced large, rapid, dose-related suppressions of feeding, but D-Phe did not. The threshold dose of L-Phe was 0.5 g/kg (32% suppression, P less than 0.01). Neither CCK nor L-Phe caused signs of illness in these experiments. The results demonstrate that intravenous exogenous CCK suppresses feeding in rhesus monkeys and suggest that endogenous CCK has the same effect; they are consistent with the hypothesis that CCK is a satiety signal.

Animals↗