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At least 19 recordsLinked to original sources
PubMed1978

Effect of staphylococcal enterotoxin B on cardiorenal functions and survival in X-irradiated rhesus macaques.

Pretreatment of rhesus macaques with nonlethal total-body x-irradiation (400 R) prolonged survival time from an average of 15 hours to 101 hours after intravenous (IV) inoculation of 50 microgram of staphylococcal enterotoxin B (SEB)/kg of body weight. Radiation exposure per se did not produce detectable cardiorenal changes; however, the longer survival after SEB challenge exposure in x-irradiated rhesus macaques was associated with improved cardiorenal functions if compared with that of nonirradiated macaques given the same dose of SEB. Total-body radiation exposure 4 days prior to IV SEB inoculation prevented typical SEB-induced decreases (where measured at 5 hours) in cardiac output, stroke volume, TcH2O, CPAH, Cosm, and urine flow, as well as increases in total peripheral and renal resistance. A theory concerning the significance of radiation-induced leukopenia on modification of SEB-induced cardiorenal functions is postulated.

Animals↗
PubMed1977

Lymphocyte subpopulations in spontaneous disease of rhesus macaques.

The immunologic status of rhesus macaques (Macaca mulatta) with naturally occurring disease was evaluated by determining the percentages of B and T lymphocytes and mitogen responsiveness of lymphocytes in peripheral blood and lymph nodes. The B lymphocytes were identified by the presence of cell surface immunoglobulin and receptors for complement. The T lymphocytes were identified by their ability to form spontaneous rosettes with sheep red blood cells. Rhesus macaques with idiopathic or primary amyloidosis had normal lymphocyte characteristics. Peripheral blood lymphocytes from rhesus macaques with atypical tuberculosis had decreased percentages of spontaneous rosette-forming cells and depressed responses to concanavalin A, and those with chronic diarrhea or chronic arthritis were also found to have abnormal peripheral blood lymphocyte characteristics. The percentage of B and T lymphocytes in normal lymph nodes was variable, making simultaneous histologic examination necessary for evaluation of diseased animals.

Amyloidosis↗
PubMed1978

Genetic variation in transferrin alleles of rhesus macaques, Macaca mulatta.

The rhesus macaque displays an extensive polymorphism at the transferrin locus. A principal components analysis describes the variance and covariance of alleles at the transferrin locus in eight widely dispersed sample populations. Using an eigenvectorial representation of the covariance matrix and systematically approximated geographical locations the distribution of populations and transferrin alleles is compared. Alleles with high variance prove to be the determining factor in the placement of populations in a "genetic map" and provide a means for interpreting the low congruence of genetics and geography found.

Alleles↗
PubMed1977

Comparison of cardiorenal functions between women and female rhesus macaques.

Selected cardiorenal functions for conscious and chaired rhesus macaques were compared directly and indirectly with corrections for body weights and surface areas to well-established base-line values for human subjects. Certain functional differences between species and conditions of measurement do not allow all experimental results from the rhesus macaque to be extrapolated to man. However, this comparative study provides evidence that can be useful in attempting to evaluate cardiorenal data from macaques in relationship to human studies.

Animals↗
PubMed2026

Pre-clinical immunogenicity and safety evaluation of H2 strain Hepatitis A Inactivated Vaccine in rhesus macaques.

BACKGROUND: Hepatitis A is a viral infection of the liver that can cause mild to severe illness. Currently, two types of HAV vaccines are used worldwide, inactivated hepatitis A vaccines, which are used in most countries, and live attenuated vaccines (H2 and L-A-1 strain), which are mainly used in China. The major disadvantage of live attenuated virus to cause secondary infections among contacts and mutation shifts of the live vaccine strain. The H2 strain was selected for the development of an inactivated hepatitis A vaccine to further reduce biosafety risks. Rhesus macaques high genomic homology with humans and the incubation period after hepatitis A vaccination and human natural infections are similar. We use rhesus macaques to assess immunogenicity and safety of the H2 strain Hepatitis A Inactivated Vaccine. METHODS: The vaccine was assessed in rhesus macaques, divided into four groups (n = 10 per group): the control group (adjuvant buffer; aluminum content 0.35 mg/mL; 2 mL per dose), the low-dose group (320EU, 0.5 mL of 640EU/mL with aluminum content 0.35 mg/mL), the medium-dose group (640EU, 1 mL of 640EU/mL with aluminum content 0.35 mg/mL), and the high-dose group (1280EU, 2 mL of 640EU/mL with aluminum content 0.35 mg/mL). Animals were injected intramuscularly at multiple sites in the hind limbs and received four inoculations at 4-week intervals. Test items including Clinical indicators, immunogenicity indicators and Histopathological examination. RESULTS: No abnormalities were observed in any group in terms of general clinical condition throughout the study period except for slight decreases in body temperature after immunization. Hematological parameters, serum biochemistry indices, and histopathological findings showed fluctuated to different degrees of fluctuation after immunization across all groups. Immunogenicity assessments showed that the inactivated hepatitis A vaccine (H2) induced both humoral and cellular immune responses effectively, and the levels of antibodies increased with certain dose- and time-response trends. CONCLUSION: The inactivated hepatitis A vaccine (H2 strain, human diploid cell) was safe and immunogenic in non-human primates. The results provide strong preclinical support for the further clinical development of this vaccine candidate.

Animals↗
PubMed2025

Proteomic Characterization of the Rhesus Macaque Lens Nucleus: Similarity to Human Lens, Age Effects on Protein Solubility, and Trends in Post-Translational Modifications.

PURPOSE: Proteomes of lens nuclei from young (4 years old) and old (15-16 years old) rhesus macaques (Macaca mulatta) were analyzed to determine similarity of the proteomic profile to that of human lenses, age-related differences in protein solubility, and association of various post-translational modifications with age and protein solubility. METHODS: Lens core proteins were separated into water-soluble and water-insoluble fractions using aqueous buffer and centrifugation. The water-insoluble fraction was solubilized using sodium dodecyl sulfate (SDS). Proteins were processed using S-trap columns, and peptide digests were analyzed using high-resolution, label-free data-dependent acquisition (DDA) proteomics. Open modification searches were performed using MSFragger to identify possible post-translational modifications (PTMs). The number of modified peptide tandem mass spectra confidently assigned to samples by age or solubility were compared to find PTMs with statistically significant count differences. RESULTS: The overall proteomic profile of rhesus macaque lenses was very similar to human lenses, consisting of 80.2% crystallins, 1.1% beaded filament proteins, and 18.7% other proteins. The crystallin fraction consisted of 27% alpha crystallins, 67.6% beta/gamma crystallins, and 5.4% taxon-specific psi crystallin. Glycolytic enzymes, beta/gamma crystallins, and a few glutathione-related enzymes were found to have age-related shifts to the water-insoluble fraction. There were significant differences in deamidation, dioxidation, carbamylation, carboxymethylation, and trioxidation based on age and/or solubility of proteins. CONCLUSIONS: These data indicate a high level of conformity between rhesus macaque and human lens proteomes, and a few key differences. We identified several age-related differences in protein solubility and PTM that may contribute to lens pathology.

Animals↗
PubMed1978

Cellular immunologic studies of malignant lymphoma in rhesus macaques.

Cells from malignant lymphoma in 10 rhesus macaques were examined for lymphocyte surface markers. Three had features of T cells, 5 had features of B cells, and 2 lacked evidence of either B- or T-cell differentiation. Correlation between the histologic classification of cell type and the B- or T-cell nature of the neoplasms was not evident. Evaluation of serum electrophoresis, mitogen responses tests, and previous histologic studies suggest that the development of the neoplastic lymphocyte proliferation occurred following or during an abnormal immunologic response.

Animals↗
PubMed2026

In vivo genome editing of central nervous system SIV reservoirs in ART-suppressed rhesus macaques.

Latent human immunodeficiency virus type 1 (HIV-1) reservoirs in the central nervous system (CNS) may sustain viral persistence and neuroinflammation contributing to HIV-associated neurocognitive disorders (HAND) despite suppressive ART. AAV9-delivered CRISPR has successfully edited SIV proviral DNA in peripheral tissues with acceptable safety profiles, but the extent of in vivo genome editing in the brain remains unclear. Using SIV-infected rhesus macaques, we mapped intact proviral DNA across CNS regions and tested systemic AAV9-CRISPR-Cas9 targeting conserved sites within Ψ packaging signal and Gag region. Ten adult rhesus macaques were infected with genetically barcoded SIVmac239, suppressed with ART, then randomized to receive intravenous AAV9-SaCas9 with dual gRNAs (Ψ + Gag) or a Cas9-only control. At necropsy after viral rebound, SIV genomes were detected in multiple brain regions as well as lymphoid tissues, confirming the CNS as a persistent reservoir during ART. Barcode analysis revealed region-specific patterns consistent with compartmentalized CNS persistence. In CRISPR-treated animals, proviral editing was measurable across anatomically distinct CNS sites. These findings demonstrate that intact and potentially replication-competent virus persists in the primate brain under ART and that systemic AAV9-CRISPR can reach and edit proviral DNA in this sanctuary, supporting genome editing as a strategy toward durable remission of CNS reservoirs.

ART↗
PubMed1976

Cardiovascular and renal functions in normal rhesus macaques.

Techniques on measurements of cardiovascular and renal functions in conscious rhesus macaques (Macaca mulatta) are described, and normal base line values are presented. The determinations included blood pressure, cardiac dynamics, total peripheral resistance, renal metabolism, renal concentrating capcity, acid-base balance, and renal handling of electrolytes.

Acid-Base Equilibrium↗
PubMed1979

Mother-infant separation in group-living rhesus macaques: a hormonal analysis.

Adrenocortical responsiveness to separation in group-living rhesus macaque mother-infant pairs was determined. Cortisol evaluations were complemented by behavioral observations of mother-infant interactions and group social behavior. Infants, but not their mothers, showed cortisol elevations that could be attributed specifically to separation. Steroid-behavior relationships suggested that the infants of high dominant mothers evinced the greatest adrenocortical response to separation. These data exemplify the complexities involved in determining endocrine/behavior relationships in a group-living situation.

Animals↗
PubMed2026

Inferring the demographic history of Chinese and Indian rhesus macaque (Macaca mulatta) populations from PacBio HiFi long-read sequencing data.

The rhesus macaque (Macaca mulatta) is one of the most widely used animal models in biomedical research, both as it resembles humans in key biological aspects and as it is characterized by a broad geographic range. Most of the individuals housed in U.S. research colonies have been sampled from either China or India, though notably the source population of these animals has significantly shifted over time. Given the substantial genetic and immunological differences between these populations, a deeper understanding of the underlying population structure is critically important for biomedical interpretation. Despite this, the demographic histories of these two populations remain poorly resolved. Here, we present an analysis of whole-genome, PacBio HiFi long-read sequencing data from ten unrelated individuals of each population, applying four related model- and non-model based demographic inference approaches, in order to reconstruct their ancestral history. We evaluated the fit of the subsequently estimated models against the empirical data, and incorporated underlying uncertainty in the mutation rates used for scaling. We inferred a well-fitting population history characterized by substantial structure between Chinese and Indian populations, with a split time ∼140,000 generations ago from an ancestral population of ∼65,000 individuals. We additionally inferred the subsequent history of size change within, and gene flow between, these populations, reaching the current estimated sizes of ∼220,000 individuals in the Chinese population and ∼14,000 individuals in the Indian population. The robust baseline demographic model established in this study will serve as a valuable resource for future research on this species, including for improved fine-scale recombination mapping, selection inference, and association studies.

Cercopithecidae↗
PubMed1978

Distribution of tissue water and electrolytes in normal rhesus macaques.

Techniques for the determination of water and electrolytes in individual tissues of normal rhesus macaques (Macaca mulatta) are described. Base-line values are presented for intracellular and extracellular distributions of water and electrolytes in 14 tissues, including skin, skeletal muscle (gastrocnemius), cardiac muscle (left ventricle), lung, diaphragm, liver, renal cortex, outer medulla and inner medulla, cerebral cortex, cerebellum, thalamus-hypothalamus complex, medulla oblongata, and spinal cord.

Animals↗
PubMed1979

Effects of intravenous injection of leukocytic endogenous mediator on cardiohepatic functions in rhesus macaques.

A crude preparation of leukocytic endogenous mediator administered IV over a 10-minute period into a rhesus macaque at a dosage of 10 ml/kg of body weight resulted in hypotension, tachycardia, vasodilation, hypoalbuminemia, and hypoproteinemia. Decreases in cardiac and hepatic functions and biphasic changes in peripheral polymorphonuclear leukocytes also were seen. All measured changes, except hepatic functions and plasma albumin values, returned to base-line values within 24 hours. Data indicate that presently utilized crude leucocytic endogenous mediator preparations contain a heretofore undescribed, and as yet unidentified, component. Induced early cardiovascular changes may be related in part to certain compounds likely to be in the crude preparation.

Animals↗
PubMed1979

Responses of immune and nonimmune adult rhesus macaques (Macaca mulatta) to adenovirus SV-20.

Adenovirus SV-20 (ASV-20) was inoculated subcutaneously into adult rhesus macaques (Macaca mulatta), and various immunologic parameters were studied. Similar changes were observed in macaques that had anti-ASV-20 serum-neutralizing antibodies prior to inoculation and in those lacking detectable antibodies. There were absolute decreases in numbers of peripheral blood lymphocytes (PBL), erythrocyte-rosetting lymphocytes, complement-receptor lymphocytes, and Fc-receptor lymphocytes. These changes were most significant (P less than 0.05) on postinoculation days (PID) 3 and 7. Mitogenic responsiveness to concanavalin A, phytohemagglutinin, and pokeweed mitogen in cultured PBL from immune and nonimmune macaques was depressed on PID 3, 7, and 14. Ultraviolet-inactivated ASV-20 caused moderate suppression of phytohemagglutinin-induced mitogenesis when viral particles and lectin were added simultaneously to PBL cultures. Plasma cortisol (hydrocortisone) values were not significantly altered following inoculation of ASV-20. High titers of anti-ASV-20 antibody developed by PID 7 in nonimmune macaques, and previously immune macaques showed a booster effect in the same time period. Antibody titers were still increased 120 days after inoculation. There was no clinical evidence of an adverse effect of ASV-20 infection in these macaques.

Adenoviridae↗
PubMed1978

Effect of staphylococcal enterotoxin B on cardiorenal functions in rhesus macaques.

Selected cardiovascular and renal functions were measured for 5 hours in conscious, chair-restrained, female rhesus macaques (Macaca mulatta) after IV (0.05 and 1.0 mg/kg) or oral (1.0 mg/kg) administration of staphylococcal enterotoxin B (SEB). Cardiovascular functions, renal hemodynamics, and renal metabolism were also studied between 6 and 11 hours after IV SEB inoculation. Oral SEB produced few changes in cardiorenal functions. In contrast, IV SEB produced hypotension, tachycardia, increased total peripheral and renal vascular resistance, and decreased cardiac and renal functions. The early significant (P less than 0.05) renal depression was not associated with hypotension (mean arterial blood pressure greater than 100 mm of Hg). However, all measured renal functions except extraction ratio of PAH were positively correlated with decreased blood pressure (r = 0.52 - 0.71) in the later phase of SEB toxemia. It is concluded that the kidney is one of the organs affected by IV SEB. Renal impairment may partially contribute to death during SEB enterotoxemia in macaques.

Animals↗
PubMed1977

Chronic bile duct cannulation of rhesus macaques (Macaca mulatta) without causing biliary fistulas.

Two surgical procedures were used for establishing chronic bile duct cannulations in rhesus macaques (Macaca mulatta) while maintaining an intact enterohepatic circulation for use in metabolism studies. One procedure resulted in the formation of biliary fistulas in all of the animals, whereas the other procedure allowed successful maintenance of the macaques without fistulation for up to 8 months after surgery. The possible importance of pressure against bile outflow in the development of the fistulas was discussed.

Animals↗
PubMed1977

Pulmonary functions in conscious and anesthetized rhesus macaques.

Techniques for measurements of selected pulmonary functions for a period of 6 hours in conscious and lightly anesthetized rhesus macaques are described. Among all variables measured, only higher PaCO2 (367 +/- 32 mm of Hg) occurred in macaques breathing O2 as compared with those breathing room air. Tidal volume, respiratory rate, minute volume, O2 consumption, and specific ventilation in conscious and anesthetized monkeys were not significantly different. Further, respiratory and metabolic values from lightly anesthetized macaques in the present study agree well with the reports of others. However, differences were the higher values for O2 consumption, tidal volume, respiratory rate, and minute volume obtained with the presently described techniques as compared with certain reported data.

Anesthesia↗