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PubMed1979

The effect of histamine-1 and histamine-2 antagonists on airway responses to histamine in the rhesus monkey.

This study used rhesus monkeys with consistent respiratory responses to aerosolized histamine. Two systems of histamine challenge were evolved to study the effects of histamine antagonists on the histamine-induced respiratory response. One system consisted of administering increasing subreactive concentrations of histamine until an airway response (H) occurred. This threshold histamine dose was repeated (H'). The pulmonary function changes occurring with the H' challenge were less intense than those with H. M, a histamine-2 receptor antagonist, when given before the H' dose was associated with a potentiated H' response compared with the threshold H response. This provides evidence for histamine-2 receptor sites in rhesus monkey airways. A second system used duplicate histamine challenges with a known reactive dose of histamine. In this system, the pulmonary function changes occurring with the repeated challenge (H') were greater than with the first reactive challenge dose (H). This H' response was inhibited partially with diphenhydramine, a histamine-1 receptor antagonist. These two systems of histamine challenge provide an experimental model for evaluating pharmacologic alteration of histamine-induced respiratory responses. There is evidence for the existence of histamine-1 and histamine-2 receptor sites in the airways of the rhesus monkey.

Animals↗
PubMed1989

In vitro fertilization and embryo transfer in the rhesus monkey.

Twenty-three rhesus monkeys were subjected to 9 days of ovarian hyperstimulation with sequential exposure to human follicle-stimulating hormone (hFSH) and then human luteinizing hormone (hLH) + hFSH. Six animals (26%) did not exhibit sustained, elevated levels of circulating estradiol, primarily due to the occurrence of a premature surge of endogenous LH (n = 4). Seventeen animals (74%) responded with supraphysiologic levels of circulating estradiol (peak value: means = 4480 pg/ml) and received human chorionic gonadotropin (hCG) on Day 10. Oocytes were collected 26 h later by aspiration of large antral follicles. Oocyte quantity (means = 18/animal) and quality (63% mature) were evaluated by in vitro fertilization (IVF), embryonic development, and embryo transfer to foster mothers. Modified conditions for the successful fertilization of oocytes used a Tyrode's augmented (TALP) medium supplemented with 0.3% bovine serum albumin (BSA). Oocytes were inseminated at the metaphase II stage with ejaculated, washed sperm (50 100 x 10(3)/ml) preexposed at ambient temperature to caffeine and dibutyryl cyclic adenosine 3'5'-monophosphate. Successful fertilization ranged from 26% to 75%. In one experiment, 5 of 11 embryos produced by IVF developed in vitro to hatched blastocysts. Embryo freezing employed a propanediol-based protocol and was applied to early cleavage-stage embryos with 100% (5 of 5) post-thaw survival. Two frozen-thawed embryos were transferred transtubally on 3 occasions into rhesus monkeys during the early luteal phase of spontaneous menstrual cycles. One pregnancy resulted, which proceeded normally to the unassisted delivery of a male offspring 170 days after the LH surge. We conclude that this sequential regimen of human gonadotropins provides a cohort of oocytes from rhesus monkeys that will complete meiotic maturation and fertilize in vitro, with embryonic development proceeding in vitro and in vivo. The production of putative antibodies to human gonadotropins, assessed by the presence of Protein A-precipitated hCG binding components in sera, limits the repeated use of monkeys in the hyperstimulation protocol. Nevertheless, this model system should facilitate further studies on oocyte maturation, fertilization, and early embryogenesis in primates.

Animals↗
PubMed2001

Subtoxic hepatic vitamin A concentrations in captive rhesus monkeys (Macaca mulatta).

Although the rhesus monkey (Macaca mulatta) is a widely used experimental animal, its exact vitamin A requirement is unknown. An amount of 430-3600 IU/d [129-1080 retinol equivalents (RE)] is recommended, largely on the basis of depletion studies. Normal hepatic vitamin A appears to be 1 micromol/g liver. Our goal was to determine hepatic vitamin A concentrations of captive monkeys. Liver autopsy samples from rhesus and marmoset (Callithrix jacchus) monkeys were obtained from the Wisconsin Regional Primate Research Center. The rhesus monkeys consumed a diet with 40 IU (12 RE) retinyl acetate/g. Male and female monkeys consumed an estimated 250 and 175 g diet/d, respectively. Marmosets were fed a powder-based diet consisting of 20 IU (6 RE) retinyl acetate/g. The marmosets consumed an estimated 25 g of the diet/d. Liver samples were extracted and analyzed by HPLC. The vitamin A concentration of the rhesus monkey livers was very high at 17.0 +/- 6.3 micromol/g. The hepatic vitamin A of the marmosets was 1.25 +/- 0.58 micromol/g liver. Histologic examination of the livers revealed Ito cell hypertrophy and hyperplasia in the rhesus monkeys compared with the marmosets. Considering that the natural diet of the rhesus monkey (fruits, seeds, roots and insects) is not high in preformed vitamin A, the vitamin A content of the diet appears excessive, supplying four times the NRC recommendation and resulting in high liver stores.

Animals↗
PubMed1997

Pit-1/growth hormone factor 1 splice variant expression in the rhesus monkey pituitary gland and the rhesus and human placenta.

We have examined the expression of Pit-1 messenger RNA (mRNA) splice variants in the nonhuman primate pituitary and in rhesus and human placenta. Full-length complementary DNAs (cDNAs) representing Pit-1 and the Pit-1 beta splice variants were cloned from a rhesus monkey pituitary cDNA library and were readily detectable by RT-PCR with rhesus pituitary gland RNA. The Pit-1T variant previously reported in mouse pituitary tumor cell lines was not detectable in normal rhesus pituitary tissue, although two novel splice variants were detected. A cDNA approximating the rat Pit-1 delta 4 variant was cloned but coded for a truncated and presumably nonfunctional protein. Only by using a nested RT-PCR approach were Pit-1 and Pit-1 beta variants consistently detectable in both human and rhesus placental tissue. The Pit-1 beta variant mRNA was not detectable in JEG-3 choriocarcinoma cells unless the cells were stimulated with 8-Br-cAMP. Immunoblot studies with nuclear extracts from primary rhesus syncytiotrophoblast cultures or JEG-3 choriocarcinoma cells indicated that although mRNA levels were very low, Pit-1 protein was detectable in differentiated cytotrophoblasts, and levels increased after treatment with 8-Br-cAMP. Two major species of Pit-1 protein were detected that corresponded to the two major bands in rat pituitary GH3 cell nuclear extracts. Low levels of slightly larger bands also were seen, which may represent Pit-1 beta protein or phosphorylated species. We conclude that Pit-1 splice variants expressed in the primate pituitary gland differ from those in the rodent gland and that the Pit-1 and Pit-1 beta mRNAs expressed in the placenta give rise to a pattern of protein expression similar to that seen in pituitary cells, which is inducible by treatment with 8-Br-cAMP.

Amino Acid Sequence↗
PubMed1975

Meningitis caused by Klebsiella spp in two rhesus monkeys.

Two adult, female rhesus monkeys (Macaca mulatta) became depressed, weak, anorectic, and adipsic. Auscultation of the thorax of 1 monkey revealed bilateral harsh rales. Neither monkey responded to therapeutic doses of antibiotics, and both died soon after treatment was started. Meningitis was demonstrated histologically and pure cultures of multiply antibiotic-resistant Klebsiella were isolated from the brains of both monkeys. Of 13 clinically normal rhesus monkeys in the same facility, 5 had multiply antibiotic-resistant Klebsiella spp in their pharynges.

Animals↗
PubMed1993

The age of biosenescence and the incidence of cerebral beta-amyloidosis in aged captive rhesus monkeys.

Autopsy surveillance of 186 rhesus monkeys aged 20 to 36 years revealed that development of major geriatric diseases such as emphysema, coronary sclerosis, and cancer increased rapidly after the age of 25 years, and nearly 70% of the monkeys in each cohort group died by 30 years. According to our 12-year longitudinal survey, the age of biosenescence in captive rhesus monkeys begins around 25 years and the maximum longevity is 36 years. The incidence of cerebral beta-amyloidosis associated with plaque formation and cerebral angiopathy was observed in 51 brains of rhesus monkeys aged 25 to 36 years. Lesions were found in 31 of 51 aged brains (60%) and 6 monkeys over 34 years of age were all severely affected. Despite the size of the plaque, nearly all of them showed immunopositive beta-amyloid. Cerebral angiopathy coexisted in 10 of 31 plaque-positive brains. The basal prefrontal gyrus was the most common site and contained the highest density of plaques, followed by the amygdala region. The amyloid in the liver, spleen, adrenal and pancreatic islets in visceral amyloidosis showed no positivity to the beta-amyloid demonstrated in the brain. As in aged human brains, the incidence of age-dependent cerebral beta-amyloidosis in captive rhesus monkeys showed great individual variation.

Aging↗
PubMed1991

Soluble human CD4 elicits an antibody response in rhesus monkeys that inhibits simian immunodeficiency virus replication.

Rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIVmac) demonstrate significant virologic and clinical improvement as a result of treatment with human recombinant soluble CD4 (rsCD4). We show that human rsCD4 does not efficiently inhibit SIVmac replication in bone marrow macrophages of rhesus monkeys and does not significantly augment bone marrow hematopoietic colony formation in vitro. However, plasma of human rsCD4-treated rhesus monkeys does exhibit significant anti-SIVmac activity in vitro. Plasma of these animals efficiently blocks SIVmac replication in peripheral blood lymphocytes and bone marrow macrophages. It also increases granulocyte/macrophage colony formation in vitro by bone marrow cells of SIVmac-infected monkeys. This plasma and the IgG fraction of plasma from a rhesus monkey immunized with human rsCD4 in adjuvant demonstrate reactivity with a soluble form of the rhesus monkey CD4 molecule, exhibit binding to CD4+ but not CD8+ concanavalin A-activated rhesus monkey peripheral blood lymphocytes, and precipitate the CD4 molecule from surface-labeled activated rhesus monkey peripheral blood lymphocytes. Moreover, anti-viral activity is demonstrable in the IgG fraction of plasma from a human rsCD4-immunized monkey. These studies raise the possibility that a modified human CD4 molecule serving as an immunogen might elicit an antibody response that could potentially induce a beneficial therapeutic response in human immunodeficiency virus-infected individuals.

Animals↗
PubMed2004

Effects of nicotine and mecamylamine on cognition in rhesus monkeys.

RATIONALE: Nicotine and other agonists of nicotinic cholinergic receptors (nAChR) have been shown to improve performance in specific memory domains in rodents and monkeys. Such beneficial effects are observed in preclinical models of age-related cognitive decline, stimulating interest in nAChR ligands as possible therapeutics. Prior work has typically focused on assays of spatial working memory in rodent studies and visual recognition memory in monkey studies. OBJECTIVE: The current study was conducted to determine the role played by nAChRs in multiple types of memory in monkeys. METHODS: Rhesus monkeys (n=6) were trained to perform a battery of six behavioral tasks and then serially challenged with acute doses of nicotine (3.2-56 microg/kg, i.m.) and the nAChR antagonist mecamylamine (0.32-1.78 mg/kg, i.m.). RESULTS: Nicotine improved performance on tests designed to assay visual recognition memory, spatial working memory and visuo-spatial associative memory, while mecamylamine impaired visuo-spatial associative memory. Ballistic and fine motor performance was not significantly improved by nicotine but fine motor performance was impaired by mecamylamine. CONCLUSIONS: Although nicotine may improve performance in multiple domains, effects on visuo-spatial associative memory is the most specifically attributable to nAChR signaling.

Animals↗
PubMed1977

Fluorescein pattern of the choriocapillaris in the neonatal rhesus monkey.

Seven neonatal rhesus monkeys were studied by serial fundus photography and fluorescein angiography at weekly intervals during the first 12 weeks of life. The neonatal rhesus showed little pigmentation of the fundus during the first six weeks of life. The fluorescein angiograms showed a definite sequential as well as segmental filling pattern at the level of the choriocapillaris. This filling pattern was based on individual units called lobules. In addition there was a segmental flow in the macula; that is, the nasal macula filled before the temporal macula.

Animals↗
PubMed2002

Isolation and characterization of a UDP-glucuronosyltransferase (UGT1A01) cloned from female rhesus monkey.

An isoform (rhesus UGT1A01) orthologus to the human UGT1A1 was cloned and sequenced from female rhesus monkey liver cDNA using primers designed from the human nucleotide sequences. Open reading frame analysis of the PCR-generated product encodes a 533-amino acid protein with a proposed 27-residue signal peptide. Nucleotide sequence comparison of rhesus UGT1A01 to other rhesus UGT1A isoforms detected a single-transition mutation at nucleotide 1520 (T-->C), resulting in a neutral F to S substitution at position 507. Rhesus UGT1A01 was greater than 99 and 95% identical to cynomolgus UGT1A01 and human UGT1A1, respectively. The rhesus UGT1A01 was expressed in HK-293 cells for functional analysis. Catalytic activity of UGT1A01 was determined with 7-hydroxy-4-(trifluoromethyl)-coumarin and more specific human UGT1A1 substrates (1-naphthol, beta-estradiol, 17 alpha-ethinylestradiol, and bilirubin). Expression of UGT1A01 protein was also detected by a Western blot utilizing a polyclonal antibody developed against the human UGT1A family.

Amino Acid Sequence↗
PubMed1990

Adrenal suppression and sexual initiation in group-living female rhesus monkeys.

Eight female rhesus monkeys living in an outdoor social group were studied for two menstrual cycles during the breeding season. During one cycle, adrenal steroids were suppressed for an average of 24 days using dexamethasone (0.6 mg/day) administered via subcutaneous osmotic minipumps. During the other cycle females were implanted with control pumps containing sterile water. Observers were blind to the treatments and treatment order was counterbalanced. Female sexual behavior was observed daily with each of two adult rhesus males. During dexamethasone treatment, cortisol levels were suppressed to less than 10% of control levels, and testosterone and androstenedione levels were suppressed to less than 50% of control, suggesting nearly total elimination of adrenal contribution to circulating androgen. All females showed hormonal evidence of ovulation. Adrenal suppression had no significant effect on female behavior, including approaches to the male and sexual solicits. In addition, no differences in any male behavior, including number of ejaculations, were seen between the two treatments. The continued cyclic copulation during adrenal suppression demonstrates that ovarian hormones are sufficient to modulate female rhesus sexual behavior and that adrenal androgens have little effect on the sexual behavior of intact, group-living rhesus females.

Adrenal Glands↗
PubMed1996

Lesions of acute inhaled lethal ricin intoxication in rhesus monkeys.

Five unimmunized adult rhesus monkeys weighing 5.9-6.3 kg were challenged with a precalculated, inhaled dose of 20.95-41.8 micrograms/kg of aerosolized ricin. Two males and three females either died or were killed at the onset of respiratory distress between 36 and 48 hours post-ricin inhalation and were necropsied. Consistent gross and microscopic lesions were confined to the thoracic cavity. All monkeys had multifocal to coalescing fibrinopurulent pneumonia, diffuse necrosis, and acute inflammation of airways, and nearly diffuse alveolar flooding, with peribronchovascular edema. All monkeys also had purulent tracheitis, fibrinopurulent pleuritis, and purulent mediastinal lymphadenitis. One male monkey and one female monkey had bilateral adrenocortical necrosis. We attributed the cause of death to asphyxiation following massive pulmonary alveolar flooding. The lesions of acute inhaled ricin intoxication in rhesus monkeys closely resembled those lesions reported in rats with acute inhaled ricin intoxication.

Administration, Inhalation↗
PubMed2001

Prophylactic and therapeutic effects of a humanized monoclonal antibody against the IL-2 receptor (DACLIZUMAB) on collagen-induced arthritis (CIA) in rhesus monkeys.

CIA in the rhesus monkey is an autoimmune-based polyarthritis with inflammation and erosion of synovial joints that shares various features with human rheumatoid arthritis (RA). The close phylogenetic relationship between man and rhesus monkey makes the model very suitable for preclinical safety and efficacy testing of new therapeutics with exclusive reactivity in primates. In this study we have investigated the prophylactic and therapeutic effects of a humanized monoclonal antibody (Daclizumab) against the alpha-chain of the IL-2 receptor (CD25). When Daclizumab treatment was started well after immunization but before the expected onset of CIA a significant reduction of joint-inflammation and joint-erosion was observed. A therapeutic treatment, initiated as soon as the first clinical signs of CIA were observed, proved also effective since joint-degradation was abrogated. The results of this study indicate that Daclizumab has clinical potential for the treatment of RA during periods of active inflammation and suppression of the destruction of the joint tissues.

Animals↗
PubMed1980

The A-B-O blood groups of rhesus monkeys: new observations.

A rhesus monkey family is described in which a group A offspring was born from a group AB mother and a group B male parent. Discovery of A and O genes in rhesus monkeys indicates that this species of macaques is polymorphic for the A-B-O blood groups, and not monomorphically B, as previously believed.

ABO Blood-Group System↗
PubMed2005

Reference body composition in adult rhesus monkeys: glucoregulatory and anthropometric indices.

Rhesus monkeys have been used as models to study obesity and disease. The aim of this study was to define body mass indices for underweight and obesity in rhesus monkeys. Longitudinal data collected over 8-14 years from 40 male and 26 female rhesus monkeys were analyzed. Body weight, insulin sensitivity index, and disposition index were regressed against percent body fat (%BF). A minimal %BF beyond which further loss of body weight resulted in loss of lean mass was determined to be 11.5% in older males, 8% in adult females, and 9% in younger adult males. Insulin sensitivity index and disposition index reached minimum values at 23% fat in older males, 18% in adult females, and 21% in younger adult males, indicating obesity. The estimated reference range for %BF was 9%-23% in male and 8%-18% in female monkeys, corresponding to body mass indices of 32-44 kg/m(2) for male and 27-35 kg/m(2) for female monkeys.

Animals↗
PubMed1992

Novel inclusion bodies in Betz cells of cortical area 4 of aged rhesus monkeys.

Seven adult rhesus monkeys ranging in age from 5 to 35 years were studied in an ultrastructural investigation of cortical area 4. Some Betz cells of layer 5 contained a perikaryal inclusion body (IB) of a unique and characteristic ultrastructural configuration that has not previously been described. The IBs consist of a regular array of three sets of equidistant parallel sheets and are not membrane bound. The distance between the sheets measures approximately 80 nm. The three sets of sheets intersect at an invariable angle of 60 degrees, forming a regular geometric structure. Each sheet comprises a single layer of parallel and densely packed straight filaments, which are approximately 10 nm thick. Thus the IBs present highly ordered crystalline arrays of filaments. The occurrence and number of IBs may be age related, since they appeared only in monkeys in mid to late adulthood and were most numerous in the oldest monkey.

Aging↗