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PubMed1979

Definition of two LD antigens in rhesus monkeys.

Two rhesus (Macaca mulatta) monkey lymphocyte-defined (LD) antigens have been identified using two typing cells as stiumlators in a one-way mixed leukocyte culture (MLC) assay. An analysis of the genetic behavior of these LD antigens in six rhesus monkey families revealed that both antigens were linked with RhLA. One probable recombinant indicated that the LD locus lies outside the two known RhLA-SD loci and the locus which controls the serum protein, properdin B(Bf). These two antigens, LD1 and LD2, had observed gene frequencies of 0.07 and 0.25, respectively. Neither of these two new LD antigens was significantly associated with any serologically defined (SD) antigen.

Animals↗
PubMed1986

Isolation and characterization of rhesus monkey milk lactoferrin.

Rhesus monkey milk lactoferrin was isolated and its characteristics compared with those of human milk lactoferrin in order to assess the feasibility of using the rhesus monkey as an animal model for the study of iron absorption from milk. Monkey lactoferrin was isolated from pooled monkey milk by two chromatographic steps. Concentration of lactoferrin in milk, determined by rocket immunoelectrophoresis, demonstrated similar concentrations in both human and monkey milk, 1-2 mg/ml. Immunodiffusion of lactoferrins from several species using an antibody raised to money lactoferrin resulted in a cross-reaction only with monkey and human lactoferrin. Lactoferrins from cow, sheep, goat, dog, and rat milk were not recognized by the antibody. Amino acid analysis of monkey lactoferrin showed a composition very similar to human lactoferrin, as well as a similarity in the unusual amino acid sequence at the N-terminal of the protein. The carbohydrate moiety of monkey lactoferrin was investigated and shown to contain monosaccharides in similar proportions to those reported for human lactoferrin. In our opinion, the rhesus monkey is a promising model for the study of the role of lactoferrin in iron absorption in the infant, as well as of the other proposed actions of lactoferrin.

Amino Acid Sequence↗
PubMed2003

Determinants of increased replicative capacity of serially passaged simian immunodeficiency virus with nef deleted in rhesus monkeys.

Most rhesus macaques infected with simian immunodeficiency virus SIVmac239 with nef deleted (either Delta nef or Delta nef Delta vpr Delta US [Delta 3]) control viral replication and do not progress to AIDS. Some monkeys, however, develop moderate viral load set points and progress to AIDS. When simian immunodeficiency viruses (SIVs) recovered from two such animals (one Delta nef and the other Delta 3) were serially passaged in rhesus monkeys, the SIVs derived from both lineages were found to consistently induce moderate viral loads and disease progression. Analysis of viral sequences in the serially passaged derivatives revealed interesting changes in three regions: (i) an unusually high number of predicted amino acid changes (12 to 14) in the cytoplasmic domain of gp41, most of which were in regions that are usually conserved; these changes were observed in both lineages; (ii) an extreme shortening of nef sequences in the region of overlap with U3; these changes were observed in both lineages; and (iii) duplication of the NF-kappa B binding site in one lineage only. Neither the polymorphic gp41 changes alone nor the U3 deletion alone appeared to be responsible for increased replicative capacity because recombinant SIVmac239 Delta nef, engineered to contain either of these changes, induced moderate viral loads in only one of six monkeys. However, five of six monkeys infected with recombinant SIVmac239 Delta nef containing both TM and U3 changes did develop persisting moderate viral loads. These genetic changes did not increase lymphoid cell-activating properties in the monkey interleukin-2-dependent T-cell line 221, but the gp41 changes did increase the fusogenic activity of the SIV envelope two- to threefold. These results delineate sequence changes in SIV that can compensate for the loss of the nef gene to partially restore replicative and pathogenic potential in rhesus monkeys.

Amino Acid Sequence↗
PubMed1998

The immunogenicity and efficacy of intranasally or parenterally administered replication-deficient vaccinia-parainfluenza virus type 3 recombinants in rhesus monkeys.

Immunization of rhesus monkeys with modified vaccinia Ankara (MVA) recombinants expressing the haemagglutinin-neuraminidase (HN) or fusion (F) glycoproteins of human parainfluenza virus type 3 (HPIV3) was compared with an intranasally-administered live, attenuated HPIV3 vaccine candidate, the cp45 derivative of the JS strain of wildtype HPIV3. The MVA recombinants, when given parenterally (i.m.) or as a parenteral-local (i.m. and i.t.) combination, induced an antibody response comparable to that of cp45 and protected the upper and lower respiratory tracts of the rhesus monkeys against challenge with wildtype HPIV3. When given by the i.n. route alone, the MVA/PIV3 recombinants induced a serum antibody response that was comparable to that of cp45 and induced resistance in the lower respiratory tract. Despite the ability of the intranasally-administered MVA/PIV3 recombinants to stimulate a good serological response and to protect the lower respiratory tract, they unexpectedly failed to induce a significant level of resistance in the upper respiratory tract. The live, attenuated virus vaccine candidate induced almost complete resistance in both the upper and lower tracts. The data thus identify two vaccine candidates that can protect both the upper and lower respiratory tracts of rhesus monkey, parenterally-administered MVA/PIV3 and intranasally-administered cp45. Further studies with these vaccines in non-human primates and humans should identify the relative merits of these immunogens for use in the very young infant.

Administration, Intranasal↗
PubMed1979

Turnover of human and monkey plasma kininogens in rhesus monkeys.

The normal metabolic turnover of plasma kininogens was studied by measuring the disappearance of intravenously administered radiolabeled human and monkey plasma kininogens from the circulation of healthy adult rhesus monkeys. Curves obtained by plotting log radioactivity against time could be expressed as double exponential equations, with the first term representing diffusion, and the second, catabolism. No significant difference between the turnovers of human and monkey kininogens was observed. The difference between the t1/2 of high molecular weight kininogen (25.95 +/- 1.60 h) (mean +/- SEM) and that of low molecular weight kininogen (18.94 +/- 1.93 h) was only marginally significant (P less than 0.05). In contrast, a highly significant (P less than 0.001) difference in their mean catabolic rates (1.12 +/- 0.08 d-1 for high molecular weight kininogen vs. 2.07 +/- 0.09 d-1 for low molecular weight kininogen) was observed. These differences between the two kininogens were attributed to differences in their distribution between the intra- and extravascular pools. Studies of kininogen turnover will be useful in elucidating the in vivo functions of the various kininogens in health as well as during clinical illness.

Animals↗
PubMed1986

Investigation of the heterogeneity of rhesus monkey alpha 1-antitrypsin.

Rhesus monkey alpha 1-antitrypsin (n = 144) was examined for heterogeneity by acid starch gel electrophoresis, isoelectric focusing in agarose and agarose gel electrophoresis. In contrast to other studies, no heterogeneity of Rhesus monkey alpha 1-antitrypsin could be documented using specific antisera. Rhesus monkey alpha 1-antitrypsin contained a reactive thiol. The pIs of the major isoforms of Rhesus monkey alpha 1-antitrypsin were 4.63, 4.69, 4.84 and 4.86 at 4 degrees C. No deficiency state of Rhesus monkey alpha 1-antitrypsin was detected. The six protease inhibitors in Rhesus monkey sera cross-reacted with antisera to the six human protease inhibitors.

Animals↗
PubMed1989

Interactions between simian immunodeficiency virus and Mycobacterium leprae in experimentally inoculated rhesus monkeys.

Thirty-four rhesus monkeys were inoculated with Mycobacterium leprae inoculum isolated from sooty mangabey monkeys with leprosy. Later it was learned that one of the M. leprae-donor mangabeys was asymptomatically infected with simian immunodeficiency virus (SIV). Thus, five of the rhesus monkey were coinoculated with M. leprae and SIV. Three of the five became SIV-positive and developed signs of leprosy and an AIDS-like illness. Two animals remained healthy. The coinoculated leprosy-positive rhesus monkeys developed leprosy despite serologic response patterns to M. leprae antigens that usually indicate leprosy resistance. Three (60%) of the five SIV-positive rhesus monkeys developed leprosy compared with 21% of the animals who received SIV-free M. leprae inocula. Diminished lepromin skin test responses and decreasing T-helper cell percentages were observed in SIV-coinoculated rhesus monkeys with leprosy. These observations suggest that SIV increases the susceptibility of rhesus monkeys to leprosy, possibly related to loss of T-helper cell function.

Animals↗
PubMed2002

Accurate evaluation of QT interval in conscious rhesus monkeys (Macaca mulatta) by use of Holter ECG.

The aim of this study was to determine the best method to evaluate the QT interval with respect to the heart rate in rhesus monkeys. Rhesus monkeys (Macaca mulatta) are widely used in cardiovascular research, but the characteristics of QT-RR formulas as regards rhesus monkeys has not been sufficiently related. We analyzed the physiological QT-RR relation for practical evaluation of the QT interval in conscious rhesus monkeys by use of 24-h Holter ECG monitoring. As the QT interval varies with dependency on the RR interval, 14 QT regression functions were evaluated by use of about 50 pairs of QT-RR points per animal in 5 male rhesus monkeys. The accuracy of fit with the measured data was assessed according to the minimum Akaike information criterion. Among one-parameter linear regression functions, QT = a x (RR)(1/2), where "a" is the regression coefficient, gave the best fit, which was almost comparable to that of all multi-parameter regression functions. Our results also suggest that the QTc formula derived from the square root regression function is the most practical for evaluation of QT intervals in rhesus monkeys. In conclusion, concerning the heart rate of rhesus monkeys, we propose the modification of Bazett's formula (QTc = QT x (500)(1/2)/(RR)(1/2), where the dimension of RR and QT interval is milliseconds). We believe the information herein is quite useful for cardiovascular studies on rhesus monkeys.

Animals↗
PubMed1983

Administration of luteinizing hormone-releasing hormone analogs delays ovulation without affecting the luteal function in rhesus monkeys.

Regularly cycling rhesus monkeys received, from days 1 to 6 of the menstrual cycle (1) the potent luteinizing hormone-releasing hormone (LH-RH) agonist D-Trp6-LH-RH, 20 micrograms/day; (2) the potent LH-RH antagonist [N-Ac-D-Trp1,3,D-p-Cl-Phe2,D-Phe6-D-Ala10]-LH-RH, 1 mg/day; or (3) vehicle. Whereas control animals showed normal menstrual cycles, as determined by dates of ovulation, length of luteal phases, and hormonal profiles, animals treated with either analog of LH-RH exhibited disruption of the cycles. In animals from both groups, delayed ovulation was observed (LH-RH agonist, 22, 23, 17, 19, and 20 days of the cycle; LH-RH antagonist, 22, 22, 24, and 10 days of the cycle, and one animal remained anovulatory for 65 days). Monkeys treated with either LH-RH analog showed normal luteal phase lengths (15, 15, 16, 14, and 15 days, and 15, 16, 16, and 13 days, respectively) and serum progesterone concentrations. The results of this study suggest that, in the rhesus monkey, the administration of LH-RH analogs during the early follicular phase induces a temporary cessation of folliculogenesis demonstrated by a delay of ovulation, with subsequent normal luteal function.

Animals↗
PubMed1977

Effect of a nuclease-resistant derivative of polyriboinosinic-polyribocytidylic acid complex on yellow fever in rhesus monkeys (Macaca mulatta).

Rhesus monkeys (Macaca mulatta) treated with a newly developed nuclease-resistant complex of polyriboinosinic-polyribocytidylic acid, poly-L-lysine, and carboxymethylcellulose [poly (ICLC)] did not die after challenge with virulent Asibi strain yellow fever (YF) virus. The strain of virus is sensitive to the effects of interferon in vitro and is lethal for rhesus monkeys four to six days after subcutaneous administration of 1,000 plaque-forming units of the virus. The mortality rate was reduced in monkeys initially treated 8 hr before or after inoculation of virus but was unchanged in monkeys initially treated 24 hr after challenge. Treated monkeys developed neutralizing antibody to YF virus. The successful treatment of yellow fever in a primate model with use of poly (ICLC) suggests a meaningful role for the interferon system in the host defense against this viral infection.

Animals↗
PubMed1977

Bacteriophages in live virus vaccines: lack of evidence for effects on the genome of rhesus monkeys.

Four juvenile rhesus monkeys were inoculated with 10(12) plaque-forming units of the bacteriophage phiV1 isolated from live virus vaccines. After phiV1 had been cleared from the blood, DNA's were isolated from the livers and kidneys and analyzed for the presence of bacteriophage by plaque assays, and for the presence of phiV1 DNA by DNA-DNA reassociation kinetics. No evidence was found for persistence of the bacteriophage or for replication of the phage genome in these rhesus monkeys.

Animals↗
PubMed1974

Pathobiological and behavioral effects of lead intoxication in the infant rhesus monkey.

When infant rhesus monkeys were exposed to lead via the addition of lead acetate (0.5-9 mg/kg body weight) to their formula or by the consumption of lead particles from lead-based surrogate mothers, they developed symptoms of lead intoxication within 6 weeks. Seizures, muscular tremors, and altered social interaction were the predominant changes. Visual impairment was also apparent in the more severely affected animals. In the animals showing obvious symptoms lead levels varied between 300 to 500 mug/100 ml of blood. Even in those animals having blood lead levels below 100 mug, hyperactivity and insomnia were observed. When the exposure to lead was eliminated, seizures subsided and visual impairment was reduced; however, the abnormal social interaction persisted. These animals also experienced a gradual decline in hematocrit and hemoglobin values during the period of examination. Liver and kidney biopsies obtained from these lead-exposed animals revealed characteristic intranuclear inclusions.When adolescent and adult monkeys were exposed to doses of lead acetate similar to those employed in the infant experiments, lead levels in excess of 200 mug/100 ml of blood were recorded. However, there were no obvious behavioral abnormalities observed. There were, however, numerous lead inclusion bodies in kidney biopsy specimens from these animals. These data suggest that, like man, the infant nonhuman primate is much more susceptible to lead intoxication than is the adult. The clinical and behavioral changes recorded in these infant rhesus monkeys suggest their use as an experimental model to evaluate lead intoxication.

Administration, Oral↗
PubMed1986

Characteristics of spontaneous obesity in male rhesus monkeys.

Adult male rhesus monkeys representing a wide range of adiposity were characterized according to body dimensions, eating behaviors, and endocrinologic/metabolic indices. Body fat, located most prominently on the abdomen, ranged from 30 to 61% of body weight. Three groups were formed on the basis of body composition data: Very Obese (VO), Moderately Obese (MO) and Nonobese (N). These groups did not differ in food intake, preferences for sweet solutions, or compensatory changes in food intake following consumption of sugar solutions. Glucose tolerance was normal, but fasting insulin levels and insulin response to glucose loading increased with increasing adiposity. Fasting triglyceride levels were highly correlated with insulin values and body fat. It is concluded that some adult male rhesus monkeys develop obesity without obvious differences in eating behavior and that obese monkeys, like obese humans, are at risk for diabetes mellitus and its complications.

Animals↗
PubMed1965

Operant discrimination of an interoceptive stimulus in rhesus monkeys.

Five rhesus macaques monkeys surgically prepared with Thiry small intestinal (jejunum) loops and implanted brain electrodes were restrained in primate chairs and kept on 23-hr deprivation-feeding cycle. After being trained to press a lever for sugar pills on an FR 25 schedule of reinforcement, a discrimination training procedure was established. Lever presses were reinforced during the S(D)-a non-aversive mechanical stimulus applied to the internal walls of the Thiry loop by rhythmic inflation-deflation of a small latex balloon by air at the rate of one cycle per sec at 100 mm Hg pressure. The S(Delta) was the absence of the visceral stimulation. The monkeys successfully discriminated between presence and absence of the internal stimulus. A discrimination reversal was attempted and completed on one monkey. The results clearly show operant discrimination based on an interoceptive stimulus. Cortical and subcortical EEG records reflected the onset but not termination of the visceral stimulation.

Animals↗
PubMed1984

Immunogenicity of wild and attenuated varicella-zoster virus strains in rhesus monkeys.

Thirty susceptible rhesus monkeys were inoculated with cell-free varicella-zoster virus strain OKA or strain KMcC. Both wild and attenuated strains were used. No clinical signs characteristic of human varicella were seen in any of the animals. Virus was not isolated from throat swabs, blood, or cerebrospinal fluid. Antibodies were measured by an enhanced plaque neutralization test. The wild and attenuated OKA strains produced comparable levels of antibodies for 3 months after inoculation. Attenuated KMcC strains produced lower titers than the wild strain. On rechallenge 3 months after primary inoculation animals boostered with the attenuated OKA strain developed significantly higher antibody titers than animals receiving the wild strain. Animals primed and challenged with the attenuated KMcC strains showed significantly lower antibody titers than animals which received the wild strain. The results indicate that the immunogenicity of attenuated OKA and KMcC strains in rhesus monkeys parallels the experience obtained with these strains in humans.

Animals↗