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Somatometry of newborn Macaca nemestrina.

Cranial and postcranial anthropometric data were taken on 18 male and 14 female newborn Macaca nemistrina monkeys and compared with data from the literature on other species of Macaca. The females of every species are somewhat smaller in all dimensions than the males at birth. However, they are more fully developed than males in relation to the amount of growth needed to achieve the adult form, and therefore undergo less postnatal growth than males.

Animals↗

The banded karyotypes of Macaca fuscata compared with Cercocebus aterrimus.

The karyotypes of Macaca fuscata and Cercocebus aterrimus are compared after G, C and AgNOR banding. Although it is often assumed that the 42-chromosome monkeys (species of the genera Macaca, Papio, and Cercocebus) are identical at the chromosomal level, a number of clear and consistent differences between the karyotypes of these two taxa are described. These differences include one pericentric inversion and differences in staining intensity, particularly in centromeric and pericentromeric areas. It is probable that high resolution chromosome techniques could reveal more differences between taxa in the 42-chromosome group than are now believed to exist. It is therefore probable that karyological data could provide insight into the phylogenetic relationships in this group of Old World monkeys.

Animals↗

Social development of infants of Macaca thibetana at Mount Emei, China.

The development of infant Macaca thibetana was studied at Mount Emei, China, and compared to that of other macaque species. It was found that there are many common features in the process of infant socialization in species of the genus Macaca: mothers play an important and active role, other group members influence the infants' development to a greater or lesser extent and play is a major activity in the life of infants. Some differences were found to exist, however, between macaque species. These included differences in maternal care behaviour such as 'len', leaving time and weaning time. Paternal behaviours were also found to vary within and among species. Tibetan macaque males care for infants extensively, and they may use infants as an agonistic buffer. The natural and social environment may also influence differences between macaque species in infant development.

Aging↗

A cinephotographic study of the role of the canine in limiting lateral jaw movement in Macaca fascicularis.

Three specimens of Macaca fascicularis were examined to test the hypothesis that the canines do not restrict lateral masticatory movements in these animals. The animals were filmed while chewing freely before, shortly after, and seven weeks after canine removal. Facial markers, viewed from the lateral plane, allowed for computer tracings of all mandibular movements. The maximal lateral movement of the mandible was assessed for each chewing cycle, and means were calculated for each test condition and animal. These means were compared intra-animal for statistically significant differences in lateral jaw movement before and after canine removal. No significant long-term increase in lateral movement was found in any animal after the removal of its canine teeth. We conclude that, in accordance with our hypothesis, the lateral movement during mastication did not increase significantly after removal of the canine teeth in three specimens of Macaca fascicularis. Therefore, the use of the macaque as a human model for masticatory studies requires further assessment. This study reveals that the canine teeth are not as important as previously assumed in affecting the form of the masticatory cycle in the macaque.

Animals↗

Histologic lesions in cynomolgus monkeys (Macaca fascicularis) naturally infected with simian retrovirus type D: comparison of seropositive, virus-positive, and uninfected animals.

Simian retrovirus (SRV) type D is a common cause of simian acquired immunodeficiency syndrome (SAIDS), a usually fatal immunosuppressive disease of macaques. Associated gross and histologic lesions have been well described for the rhesus macaque (Macaca mulatta) in experimental and natural infections. However, morphologic changes induced by this virus at the gross and light-microscopic level have not been documented in the cynomolgus macaque (Macaca fascicularis). In 1996, sporadic cases of anemia, weight loss, and diarrhea were noted in a colony of cynomolgus macaques in our research facility. Out of 28 animals, 24 tested positive for SRV by serology or virus isolation. Animals could mainly be classified into 1 of 2 categories: 1) positive for virus isolation but negative for SRV antibody and 2) negative for virus isolation but antibody positive. During the process of eliminating the virus from the colony, a complete postmortem examination was performed on the 24 infected animals that had to be culled. Twelve SRV-negative animals were available as controls. Minimal to mild follicular lymphoid infiltrates were seen in various organ systems in 75% of the negative animals, compared with moderate to marked infiltrates in 83% of infected animals. Lymphoid infiltrates were more common in the brain, bone marrow, and salivary gland of viremic animals and were rare to nonexistent in seropositive or negative animals. Lymphoid hyperplasia was present in 38% of the infected animals, whereas lymphoid depletion was seen in 47% of the infected animals. Overall, lesions were of greater severity in viremic animals than in virus-negative or seropositive animals. Overall, infected animals had lower, statistically significant hematocrit and lymphocyte values. Viremic animals had significantly lower hematocrit, white blood cell, lymphocyte, and neutrophil values than did controls. Only 1 out of 24 infected animals had clinical signs that were consistent with the definition of SAIDS, and none had evidence of opportunistic infections. Lesions were similar to those already reported in other species of macaques, but the absence of severe illness that was consistent with SAIDS in most viremic animals suggests that there may be a different manifestation of disease in the cynomolgus.

Animals↗

Coronary artery distribution in Macaca fascicularis (Cynomolgus).

The studies were performed using stereomicroscopic dissection, and light microscopy examination on hearts of healthy and fertile non-human primates (Macaca fascicularis) of both sexes. The results indicate that the anatomy of the coronary arteries offers points of similarity as well as departure from humans. The blood supply to the hearts was by left (LCA) and right (RCA) coronary arteries. The LCA averaged 1.78 +/- 0.29 (SD) mm (range 1.40-2.40 mm) in external diameter at its origin, and 4.34 +/- 1.29 (SD) mm (range 1.8-6.5 mm) in length. It usually terminated by dividing into a left anterior descending artery (LAD) and the circumflex branch (CXA). The CXA branch coursed along the left part of the atrioventricular groove and gave off a varying number of branches to the left ventricle and atrium along its course. It averaged 1.14 +/- 0.30 (SD) mm (range 0.70-1.70 mm) in external diameter at its origin. The LAD averaged 1.28 +/- 0.25 (SD) mm (range 0.90 +/- 1.80 mm) in external diameter at its origin. In 73% cases the LAD continued over the apex to course dorsally in the posterior interventricular groove, and gave off a varying number of diagonal and septal branches. The RCA arose from the right aortic sinus and coursed along the right part of the atrioventricular groove and averaged 0.94 +/- 0.15 (SD) mm (range 0.70-1.20 mm) in external diameter at its origin. The posterior descending coronary artery (PDCA) arose from the LCA in 55% of the cases, and from the RCA in 45%. Myocardial bridges (MB) were present in 54% of the hearts and over the LCA branches exclusively. The average length of all MB was 5.68 +/- 3.31 (SD) mm (range 2.4-11.5 mm). The coronary arteries of Macaca fascicularis are medium sized muscular arteries with well developed tunics intima, media and adventitia, and so resemble human arteries more closely than the dog. Therefore, we suggest this primate species might be a useful model for physiological studies on the coronary circulation.

Animals↗

Partial urethral obstruction enhances NADPH-diaphorase activity in the monkey (Macaca fascicularis) bladder: light and electron microscopic studies.

The effect of partially obstructing the urethra on the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity in neurons of the intramural ganglia of the monkey (Macaca fascicularis) bladder was examined by light and electron microscopy. Partial urethral ligation was done in adult male monkeys. The animals were sacrificed 2, 4 weeks after partial urethral obstruction. This was compared to controls (normal and sham operated). Urethral obstructed animals were observed to have increased urinary frequency and decreased urinary flow rate. Two weeks after urethral obstruction, the overall NADPH-d activity in the intramural ganglia of the bladder base was enhanced compared to control animals. The frequency of intensely stained NADPH-d positive neurons was increased compared to the control animals. About one-third of intensely stained NADPH-d positive neurons appeared to undergo degenerative changes. At 4 weeks after urethral obstruction, a wide occurrence of NADPH-d positive neurons in advanced stages of degeneration in the bladder base was observed. Cellular debris was strewn among normal looking ganglion cells and along the nerve processes. The proportion of intensely stained NADPH-d positive neurons was relatively lower than the controls. The total number of NADPH-d positive neurons and the nerve fibres in the entire bladder was significantly reduced when compared to control animals. Electron microscopy showed some NADPH-d activity in intramural ganglion cells in 2 weeks after partial urethral obstruction. NADPH-d reaction product (formazan) was deposited on the membranes of the rough endoplasmic reticulum, and the outer membranes of some mitochondria in the intramural neuron. At 4 weeks after urethral obstruction, NADPH-d was present in the membrane of the mitochondria and some mitochondria appeared swollen with disrupted cristae. Present results show that NADPH-d activity in neurons of the intramural ganglia of the monkey (Macaca fascicularis) urinary bladder was increased after two weeks and reduced after 4 weeks of partial urethral obstruction. It is speculated that the increased NADPH-d activity associated with partial urethral obstruction would lead to neuronal damage and death, which may contribute to detrusor overactivity. However, it warrants further investigation to understand the mechanism of neuronal cell death after partial urethral obstruction.

Animals↗

Safe and efficient collection of cytokine-mobilized peripheral blood cells from cynomolgus monkeys (Macaca fascicularis) with human newborn-equivalent body weights.

Hematopoietic stem cells in bone marrow can be mobilized into peripheral blood by cytokine administration. Cytokine-mobilized peripheral blood stem cells are of great use in clinical applications. We previously established a modified procedure for the collection of cytokine-mobilized peripheral blood cells from rhesus monkeys (Macaca mulata) using a commercially available apparatus originally developed for human subjects. In this study, we examined the efficacy and safety of this method with even smaller macaques, cynomolgus monkeys (Macaca fascicularis), which are equivalent to human newborns in body weight (mean = 3.3 kg). Using the manufacturer's unmodified protocol (n=6), one monkey died of cardiac failure and three developed severe anemia. In contrast, using our modified procedure (n=6), no such complication was observed in any animal. In addition, the harvested nuclear cell, mononuclear cell and CD34(+) cell counts were significantly higher with the modified method. The modified method should allow safe and efficient collection of cytokine-mobilized peripheral blood cells from non-human primates as small as human newborns in a non-invasive manner.

Anemia↗

Studies on sporozoite-induced and chronic infections with Plasmodium fragile in Macaca mulatta and New World monkeys.

Plasmodium fragile continues to be investigated because of its biologic similarities to the human malaria parasite, Plasmodium falciparum. Two strains of P. fragile are available for study; one strain is able to infect mosquitoes, whereas the other strain is transmissible only by blood inoculation. The Sri Lanka strain of P. fragile was transmitted to Macaca mulatta, Macaca fascicularis, Aotus lemurinus griseimembra, Aotus nancymaae, Aotus vociferans, and Saimiri boliviensis monkeys via sporozoites that developed to maturity only in Anopheles dirus mosquitoes. The prepatent periods ranged from 12 to 35 days for macaques and from 15 to 30 days for New World monkeys after intravenous injection of sporozoites. Eight rhesus monkeys were infected with the Nilgiri strain and followed for 482 days. Parasitemia in 6 animals persisted at relatively high density through the period of observation. Erythrocyte, hematocrit, and hemoglobin values reached their lowest levels 3 wk after infection and slowly recovered; however, the values did not approach preinfection levels as long as parasitemia persisted in the monkeys. The mean corpuscular volume and corpuscular hemoglobin concentration reached their peak and lowest values, respectively, at day 38 and then returned to the preinfection level. The mean corpuscular hemoglobin value decreased to its lowest level at day 87 and then returned to preinfection level.

Animals↗

Self-control in rhesus macaques (Macaca mulatta): controlling for differential stimulus exposure.

Previous research on self-control using macaques (Macaca fascicularis) showed these animals have a strong bias for a delayed, larger reinforcer (Self-control) over an immediate, smaller reinforcer (Impulsive). Typical studies of self-control have used a discrete trials methodology with a secondary discriminative stimulus during the delay periods. This results in a greater exposure to the stimulus representing the self-controlled option and may account for some of the early exclusive preference for self-control observed. The present experiment examined self-control bias in three rhesus macaques (Macaca mulatta) while controlling for differential durations of stimulus exposure. Subjects were presented stimuli via a computer monitor and made choices by touching the stimulus at which point both stimuli were removed for the delay periods. All three subjects displayed a nearly exclusive bias for the delayed, larger reinforcer self-control). These results are consistent with previous studies, despite the variations in methodology and species.

Animals↗

Complete amino acid sequence of gamma chain of fetal hemoglobin of Japanese macaque (Macaca fuscata).

The complete amino acid sequence of the gamma chain of Japanese macaque (Macaca fuscata) was deduced from sequence analysis of its tryptic peptides and a few other peptides. Three amino acid residues are substituted compared to the human gamma chain, 77His (human) to 77Asn (Japanese macaque), 104Lys to 104Arg and 135Thr to 135 Ala. The primary structure of the gamma chain of Japanese macaque is the same as that of rhesus macaque (Macaca mulatta) (2) and yellow baboon (Papio cynocephalus) (3). Difference in the structure of the gamma chain among primate species is smaller than that of beta chain.

Amino Acid Sequence↗

Pharmacokinetics of recombinant human granulocyte macrophage colony-stimulating factor in Macaca mulatta.

AIM: To examine the pharmacokinetics of i.v. and s.c. recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) in Macaca mulatta. METHODS: Plasma levels of rhGM-CSF were detected with sandwich enzyme-linked immunosorbent assay. RESULTS: Plasma concentration-time curves after i.v. rhGM-CSF in monkeys were best fitted with 3-compartment model. The 1st, 2nd, and 3rd phase T1/2 were 0.05-0.07, 0.14-0.58, and 1.4-4.1 h. Cl and K10 were similar between different doses, respectively. Cmax was 0.93 +/- 0.16 microgram.L-1, Tmax was 2.65 +/- 0.14 h, and elimination T1/2 was 2.5 +/- 0.3 h after s.c. rhGM-CSF. The bioavailability after s.c. rhGM-CSF was 0.61. CONCLUSION: Pharmacokinetics of rhGM-CSF in Macaca mulatta provided a useful index for clinical trial.

Animals↗

Cardiovascular, respiratory, thermoregulatory, sedative, and analgesic effects of intravenous administration of medetomidine in rhesus macaques (Macaca mulatta).

BACKGROUND AND PURPOSE: Medetomidine is a selective, specific, and potent alpha2-adrenergic receptor agonist that has been utilized successfully as a sedative/analgesic agent in a variety of domestic and nondomestic animals. The objective of this study was to document the physiological effects of the intravenous administration of medetomidine in rhesus macaques (Macaca mulatta). METHODS: Fifteen healthy rhesus macaques (Macaca mulatta), 5 to 15 years old and weighing 5.5 to 11.8 kg, were given four dosages of medetomidine (50, 100, 150, and 200 microg/kg of body weight) intravenously, and cardiovascular, respiratory, thermoregulatory, sedative, and analgesic effects were determined. RESULTS: All four doses of medetomidine induced a similar and significant decrease in mean arterial pressure, as well as a transient but significant increase in respiratory rate followed by a longer-lasting significant decrease. Bradycardia, hypotension, and loss of thermoregulatory ability accompanied by a biphasic respiratory response and inconsistent sedation, analgesia, and muscular relaxation were observed. Heart rate decrease was rapid for all doses, but was significantly lower and of shorter duration after administration of the 50 microg/kg dosage. CONCLUSION: The inconsistency of the anesthetic plane induced by intravenous administration of medetomidine precludes it from being used alone to sedate rhesus macaques.

Analgesia↗

[Technique for registration of auricular pulsogram in macaca mulatta monkeys].

An upgraded technique for registration of auricular pulsogram in monkeys (Macaca mulatta) has been proposed to study shifts in the common artery bed. The measurement is made with a photo-electrical sensor taped to the cartilage of the floor of the auricle and secured with a special cap and helmet of elastic net, and a system for data transfer from the sensor to a register enhanced by preamplifiers. Potentialities of the technique are exemplified by the investigation of Macaca mulatta's tolerance of +Gz loads.

Animals↗

Histopathological changes of Macaca mulatta infected with Plasmodium knowlesi.

OBJECTIVE: To study the histopathological changes of relevant internal organs of Macaca mulatta infected with Plasmodium knowlesi (P. knowlesi). METHODS: Histopathological examination of 3 monkeys who died of P. knowlesi infection, 2 P. knowlesi infected monkeys who died of treatment failure with artesunate suppository and 1 P. knowlesi infected monkey that was cured by piperaquine phosphate (PQP) but died of trauma and necrosis of the fore limb. RESULTS: The heart, liver, spleen, lung, kidney, brain, pancreas, parathyroid, pituitary and lymph nodes showed severe pathological changes in 3 monkeys (No. 1, 7 and 12) who died of P. knowlesi infection and 1 infected monkey (No. 72) who died of treatment failure with artesunate suppository. Red blood cells containing malarial parasites and pigments were concentrated in the capillaries of these organs. Malarial pigments were deposited in many organs or phagocytized by macrophages in 1 monkey (No. 131), it was cured by piperaquine phosphate but died of trauma and necrosis of the fore limb; cellular atrophy and disappearance of pancreatic islets, parathyroid and pituitary cells were also observed. One monkey (No. 33) treated with artesunate suppository, showed that blood parasites became negative but recrudesced and pituitary later died from a gavage accident. Its organs showed a significant difference to those of the infected monkeys receiving no treatment. Only the liver Kupffer cells and cerebral matrix contained malarial parasites and pigments; many relevant internal organs showed repair. CONCLUSION: The pathological changes of relevant internal organs of Macaca mulatta infected with P. knowlesi were examined in detail, especially cellular atrophy and the disappearance of pancreatic islets, parathyroid and pituitary cells and myolysis of cardiac muscles. These changes have not previously been reported elsewhere.

Animals↗

Seropositivity to HCV in Macaca fascicularis.

Several non-human primate species are used as laboratory animals for research purposes. Non human primates represent a potential hazard for laboratory animal handlers as they exceed all other species in importance as potentiators of disease in laboratory personnel (Quist K.D., 1972). Hepatitis viruses cause some of the prevalent diseases in man which constitute an important public health problem. The first outbreak of the infection was related to non human primates and occurred in 1958-1960 in USA, with more then 200 human cases. Chimpanzee is the main species that has been implicated but others have also been involved. We report a case of seropositivity to HCV antigens in Macaca fascicularis using a third generation RIBA assay. The nature of reactivity of the positive samples could not be resolved as no animal in the breeder colony had been exposed to an HCV source. Furthermore, Macaca spp. did not appear to be a susceptible species in previous studies.

Animals↗

[A comparison of the microvascular architecture of the knee joints of humans and Macaca mulatta].

The blood supply and the microvascular architecture of the knee joint in Macaca mulatta were investigated. 24 lower limb specimens were injected with a barium sulfate suspension via the common iliac artery. The results were then compared with human knee joint data obtained by other authors. We found no evident difference in knee joint blood supply between the two species, but a few variances did exist. Therefore we considered it correct to use the knee joint of the Macaca mulatta as a model in medical experiments, but in an experiment on the regional area or some structures of the knee joint, several variances must be considered before drawing conclusions.

Animals↗

Scanning electron microscopic analysis of dental wear on the heavily worn second molars of the wild Japanese monkey (Macaca fuscata).

Microscopic features on scanning electron micrographs of epoxy-replicas of the second molars of nine wild-caught adult female Japanese monkeys, Macaca fuscata, from Oita Takasakiyama, Kyushu, were measured using a digitizer. These monkeys had been fed a monkey-diet during three or four days of captivity before replicas were made. Six of these specimens showed such heavily worn second molars that narrow peripheral enamel bands surrounded large dentin exposures and the cusps of the others had been worn off. Microwear measurements from sites near facet 9 were compared with those of facet 9 of three kinds of hard-object feeding primates from the literature. The mean percentage of pits among all features (pits and scratches) in these samples was almost equal to those that have been reported previously for Pongo pygmaeus and Cebus apella, but tended to be smaller than those of Cercocebus albigena. The mean pit width of these specimens was larger than that of Pongo pygmaeus and was almost equal to those of Cercocebus albigena and Cebus apella. The mean scratch width of these samples was larger than those of Cebus apella and Pongo pygmaeus. These features and the significant differences between these samples and the nonhard-object eaters such as Colobus guereza place these Macaca samples in the category of hard-object feeders. Additional directly observed seasonal feeding behaviors that would confirm the dietary contribution to these features is now needed.

Animals↗