A longitudinal study of age-specific reproductive output and body condition among male rhesus macaques, Macaca mulatta.

In many mammalian species, male reproductive success appears to climb sharply at young adulthood, form a brief plateau during prime ages, and decline among older animals, a pattern often attributed to reduced physical condition with ageing. However, solid evidence to either substantiate or refute this profile among nonhuman primates is lacking. Here, we combine a decade of genetic analysis of paternity among free-ranging rhesus macaques, Macaca mulatta, with information about body condition in order to evaluate how changes in morphology might govern age-specific reproduction among males. We show that age-specific reproductive success traverses the same life history profile as found in other mammals, but reductions in reproductive output with advanced age were associated with reduced chances of survivorship rather than accompanied by diminished body condition. We demonstrate that variance in male age at onset of reproduction is three times greater than variance in female age at onset of reproduction. We provide the first evidence from primates that age-specific reproductive output among males is not a consequence of age-related changes in body condition, but reflects social and demographic factors.

Multiple sirehood in free-ranging twin rhesus macaques (Macaca mulatta).

Rhesus macaque females regularly copulate with a number of partners, and produce a single offspring per reproductive cycle in over 99% of cases. We used genotyping of 10 STR markers to determine paternity in the Cayo Santiago population of rhesus macaques. About 1,500 monkeys have been analyzed to date, with their marker genotypes entered into a computerized database. These data enable us to report the first documented case in any cercopithecine nonhuman primate species of the production of twin offspring sired by different males.

Slow cluster formation of purified human or rhesus T cells requires protein kinasse C and LFA-1

Ab: Homotropic T cell adhesion, as generally studied, consists of a rapid, transient binding process that is measured over a 15-120 min. period. Here we report a slow type of adhesion process occurring with human or rhesus T cells, purified from peripheral blood, that manifests itself by the formation of rounded, multi-layer clusters which may contain hundreds of cells. The maximal number and size of the clusters peak 1-2 days after the addition of phorbol ester, an absolute requirement. The number of clusters formed is proportional to phorbol ester concentration up to 1.25 ng/mL. Phorbol esters such as phorbol myristate acetate (PMA), phorbol dibutyrate (PDB), and 7-octylindolactam (OIL) induced optimal cluster formation at 1-13 ng/mL, levels slightly higher than that required to induce mitogenesis of purified T cells. Phorbol itself and the alpha-form of the ester were inactive. Both cluster formation and mitogenesis (stimulated by Con A or anti-CD3) are completely inhibited by staurosporin at 12.5 ng/mL. Even at 2.5 ng/mL, 74 percent of cluster formation was inhibited, which strongly implies a crucial role for protein kinase C. In the presence of accessory cells, T cell clusters were suppressed. Monoclonal Ab such as anti-CD3, mouse anti-CD3 followed by anti-mouse IgG, anti-CD4, anti-CD4A, anti-CD2, anti-CD8, and anti-CD45 did not induce cluster formation. None were inhibitory or stimulatory in the presence of PMA, except for anti-CD3 which enhanced cluster formation by 26 percent. However, anti-LFA-1 beta-chain (mouse monoclonal) completely blocked cluster formation over the range studied (63-1000 ng/mL) for both human and rhesus cells; rat anti-LFA-1 only blocked human cell adhesion. Anti LFA-1 only partially inhibited T cell mitogenesis. These results show that slow cluster formation shares the LFA-1 and phorbol ester requirements of the rapid adhesion of T cells requiring LFA-1 and ICAM-1. However, cluster occurs at a very low phorbol ester concentration, appears more sensitive to staurosporin inhibition, and is not stimulated via the TCR receptor like the rapid adhesion process. We hypothesize that certain neuronal processes, induced by phorbol ester, and which also show a similar protein kinase C activation time course, may share mechanisms in common with cluster formation

In vitro HIV infection of primate lymphocytes

El propósito de este estudio fue el de evaluar la capacidad de los virus del SIDA (VIH-1 y VIH-2) para multiplicarse en las células mononuclearres de la sangre periférica (CMSP) de cuatro especies de primates. CMSP de Cebus apella, patas (Erythrocebus patas), monos verdes (cercopithecus aethiops sabeus) y rhesus (Macaca mulatta) fueron infectados "in vitro" con VIH-1 y con VIH-2. La multiplicación de estos virus se determinó midiendo la actividad de la enzima retrotranscriptasa en los cultivos infectados. Ambos virus produjeron efectos citipáticos en dichos cultivos. Se observó un bajo nivel de multiplicación de los virus VIH-1 y VIH-2 en las células provenientes de monos Cebus. Sin embargo, el virus VIH-2 se multiplicó eficientemente en CMSP de monos rhesus. La capacidad que posee el virus de la inmunodeficiencia humana tipo 2, (VIH-2) de multiplicarse en estas células, podría ser utilizada para en la evaluación "in vivo" de productos antivirales y de vacunas

Metabolic abnormalities among free-ranging Macaca mulatta on Cayo Santiago: Comparisons with Macaca mulatta at Sabana Seca.

Free-ranging rhesus macaques (Macaca mulatta) were examined on the island of Cayo Santiago (CS), Puerto Rico, with intravenous glucose tolerance tests (IV-GTTs). Results were compared to monkeys derived from the island, but subsequently housed in corrals or gang cages at Sabana Seca (SS). Glucose clearance was similar among CS and SS macaques (range 2.99 to 4.50%min); both CS and SS males had significantly greater fasting serum glucose levels (63 ± 1 and 61 ± 2 mg/dl, respectively) than females; concentrations in CS and SS nonpregnant females (49 ± 3 vs. 52 ± 1 mg/dl) were significantly greater than CS and SS pregnant females (38 ± 3 vs. 41 ± 2 mg/dl) at each location. Fasting insulin was significantly less for male CS than for male SS macaques (means of 34 vs. 51 µU/ml); female averages were similar at both locations (range 48 to 61 µU/ml). The acute increment of insulin secretion for CS males was less than for SS males (85 vs. 136 µU/ml) but there were no differences between CS and SS females. The weight and body mass of CS macaques were generally greater than SS macaques. Hyperinsulinemic macaques > 10 years had greater weight and body mass compared to age-matched controls. Genetics may play a major role in expression of these impairments since the incidence on CS varied from 0 to 54% among the matrilines examined.

Parasites of free-ranging Cayo Santiago macaques after 46 years of isolation.

Three hundred and thirty seven Macaca mulatta from a population that had been isolated on a small island off the coast of Puerto Rico for 46 years were examined for parasites. Anatrichosoma cynamolgi (26%), Strongyloides fuelleborni (54%); Trichuris trichiura (23%); and Balantidium coli (2%) were detected. Toxoplasma antibodies were found in 10% of the sera examined. Milk was examined for Stronglyloides, and blood was examined for microfilariae and protozoa, but no parasites were found in these specimens. The animals in this colony harbored intestinal parasites but were in excellent physical condition, with a high reproductive rate and a low mortality rate. It is concluded that the presence of intestinal and tissue parasites has little measurable effect on the overall health of rhesus in this free-ranging environment.

Effect of tetanus toxoid inoculation on mortality in the Cayo Santiago macaque population.

Tetanus was a major cause of mortality in the free-ranging population of rhesus monkeys (Macaca mulatta) on Cayo Santiago. From 1977 to 1984 the mean (±1 SD) annual total mortality rate (excluding neonatal deaths within 48 h postpartum, abortions, and stillbirths) was 6.39% ± .94%, and the mean annual tetanus mortality rate was 1.33% ± .45%. Tetanus deaths accounted for 19.5% of the total mortality in the colony. In 1985, all monkeys on the island, except infants and six adult monkeys, were given primary inoculations of tetanus toxoid. The following year, boosters were administered, and yearlings received primary inoculations. One fatal case of tetanus and one recovery from mild disease occurred in uninoculated adult monkeys in 1985, but no additional cases have been observed since. For 1985-1986 the mean annual total mortality rate was 3.69% ± .05%, and the mean annual tetanus mortality rate was .08% ± .08%. Thus, during the 2 years after inoculation against tetanus, the mean annual total mortality rate and the mean annual tetanus mortality rate declined by 42.2% and 94.0%, respectively, when compared to the 8-year period (1977-1984) prior to inoculation. These differences were significant [(χ2 = 12.48; P < .005), (χ2 = 16.94; P < .005)]. The elimination of tetanus infections through mass inoculation of the Cayo Santiago colony is expected to have a profound impact on the demography of the population by increasing the rate of population growth, by decreasing the differential rates of increase of the component social groups, and by changing the age distribution of the population.

Leptospiral agglutinins in the Cayo Santiago macaques.

The colony of free-ranging rhesus monkeys (Macaca mulatta) on Cayo Santiago, Puerto Rico, was surveyed for leptospiral agglutinins. Only 5 (3%) of 169 monkeys (25% of the population) were seropositive (titers of ⩾ 1:100). An additional 29 animals (17%) had titers ⩽1:50. The proportions of seropositive males and females were 22% and 18%, respectively, and twice as many adult as immature animals (32% vs. 15%) were positive. In most seropositive monkeys a single serogroup predominated, Icterohaemorrhagiae being recorded in nearly 60% of these animals. In a follow-up survey conducted a year later, 4% of 158 of the original monkeys were seropositive, with titers of from 1:100 to 1:200. None of 22 Rattus rattus captured on Cayo Santiago had agglutinins to pathogenic serovars. Despite contact with rats and ingestion of stagnant water, the serological evidence, the excellent clinical condition, low mortality, and high reproductive rates of the Cayo Santiago macaques indicate that leptospirosis is not a health problem in this free ranging monkey colony.

Clolesterol and dominance rank in the Cayo Santiago Macaques

La relación entre el colesterol sérico total (STC) y el rango social de dominio se investigó en machos adultos (>- 5 años) de una sola tropa formada en un ambiente fibre y natural de monos rhesus (Macaca mulatta) en Cayo Santiago, Puerto Rico. El rango de dominio, la edad y el peso corporal no se correlacionaron con STC, ni se correlacionó con la edad ni peso corporal. La media (ñ 1 SD) fue de 154.0 ñ 27.0 mg/dl. Siete de los 34 machos del muestreo tenían niveles de STC (189.1 ñ 4.3 mg/dl) mayores de 1 SD sobre la mediana para todos los machos. Estos monos no se diferenciaron significativamente en edad ni peso corporal entre ellos ni de los otros machos del estudio, pero cinco de los siete monos con STC alto eran machas de alto rango en el grupo y siete de ocho monos con STC (115.6 ñ 5.8 mg/dl) 1 SD o más por debajo de la media para todos los machos eran de bajo rango. La diferencia fue significativa (p<.05, "Fisher's Exact Test")

Carbohydrate impairment and insulin secretory abnormalities among Macaca mulatta from Cayo Santiago.

Rhesus macaques (Macaca mulatta) from Cayo Santiago were examined for evidence of carbohydrate intolerance indicative of potential development of non-insulin-dependent diabetes mellitus (NIDDM). Monkeys 6 to >20 years from natal Groups J, M, and P, an AGED Group (all >20 years), and unrelated monkeys removed from the island in association with other groups (CAYO), were examined with intravenous glucose tolerance tests (iv-GTT). Morphometric measurements were made on all tested monkeys. Impairments included fasting hyperglycemia (>115 mg/dl), impaired glucose clearance (K <2.0%/min), fasting hyperinsulinemia (>150 µU/ml) or hypoinsulinemia (<20 µU/ml), and insulin secretory abnormalities (>500 µU/ml or <75 µU/ml). Natal groups J and M had 31% with impairments, group P had 0% the AGED group had 45%, and the CAYO group had 33%. Impaired glucose clearance was usually attributable to a reduced insulin response. Impairments correlated significantly (p ⩽ 0.05) to body weight and a modified Quetelet index, but not to sex, acute stress, or islet cell antibodies; the relationships to age could not be delineated in this survey. Impairements in monkeys are indicative of various stages in the asynchronous development of carbohydrate intolerance leading to NIDDM.

Secondary sex ratio variation in the Cayo Santiago macaque population.

Secondary sex ratios (SSR) were calculated from 1,385 offspring delivered by 372 females in the Cayo Santiago population of free-ranging rhesus monkeys (Macaca mulatta) from 1976 through 1984. The SSR for the entire colony ranged from 0.86 to 1.46 males per female (combined total: 1.08), but no significant difference was observed (P > .05). SSR values were compared among the troops for each year. The SSR differed significantly among the six social groups (P < .05) only in 1978. The annual SSR of each troop was compared over 9 years. Significant variation was found only in group O. The annual SSR was significantly skewed (P < .05, males > females) for three troops in 3 separate years. The SSR did not vary according to troop rank. No significant difference was found among the 17 matrilines of the population, but comparison of matrilines within each social group revealed a significant difference in the SSR (P < .02) for the three matrilines in group I. This was due to the significantly skewed SSR (P = .0080, females > males) of the DM genealogy in that troop. SSR values were not related to matrilineal rank. Individual dominance rank did not bias the SSR. Complete reproductive histories for 266 females showed no evidence of significantly skewed SSR values. Age-related effects on the SSR were examined by using cross-sectional and cohort-based analyses. The SSR did not vary significantly (P > .05) with maternal age, but it was significantly skewed (P < .05) toward males at the ages of 5 and 9 years. Parity had no significant effect (P > .05) on SSR values. Wide variation occurred in the SSR of the Cayo Santiago population. Rank-related adjustment of the SSR at the level of the troop, matriline, or individual, as reported in short-term studies of other primate social groups, may reflect normal annual variation in the SSR evident only from longitudinal observations of large multigroup primate populations.

Climate and seasonal reproduction in the Cayo Santiago macaques.

This paper reports the results of an eight-year study of seasonal reproduction in the free-ranging colony of rhesus monkeys on Cayo Santiago, Puerto Rico. There was a significant correlation between the start of the annual spring rainy season and the estimated median conception date (r = .94, p < .001) and median birth date (r = .94, p < .001). Conceptions followed the commencement of spring rains by 70 days. Significant and negative correlations were found between the number of days from the start of the rains to the first conception (r = -.93, p < 0.01) and median conceptions (r = -.91, p < .01). When spring rains were delayed, the interval between the onset of rains and conceptions decreased linearly. The median birth date for the Cayo Santiago population was accurately predicted for 1984 using two methods. When results from Cayo Santiago were applied retrospectively to data from the colony of rhesus monkeys near La Parguera, Puerto Rico, it explained the three-month difference in seasonality of reproduction between the two populations located at the same latitude (18°N). Photoperiod, as a function of latitude, appears to set the temporal limits of seasonal reproduction in rhesus macaques, while the onset of spring rains regulates reproductive activity within that range, at least in the Cayo Santiago population. The biological channel through which the effect is mediated has not been identified.

In vivo transfer of ascorbate and dehydroascorbate to the aqueous humor of the eye in the domestic cat and the rhesus monkey

Se ha estudiado in vivo, en gatos domésticos y en macacos thesus, la incorporación de ascorbato y dehidroascorbato (DHA) al humor acuoso.l En el gato se encontró que los niveles de ayunas de ascorbato en el humor acuoso (1.49 mg%) se mantienen unas 6 veces por encima de los séricos, lo cual se ha tomado como undcación de la existencia de un proceso de transporte activo para ascorbato en el cuerpo ciliar de este animal. También se ha determinado que la transferencia de ascorbato al humor acuoso en el gato tiene dos componentes, uno saturable, mediado, con parámetros cinéticos Tm = 4.9 mg% y Kt = 0,53 mg%, que debe ser responsable del transporte activo, y otro que nos es saturable, sino tipo difusión sencilla. En el mono se detectó un sistema de transporte mediado, sin componente difusivo, con Tm = 22.6 mg% y Kt = 0.28mg%, y capaz de mantener en el humor acuoso una concentración de ascorbato 25 veces mayor que en el plasma. Los valores de ayunas de ascorbato en el suero del mono (0.69 mg%) se mantienen sobre el suero del mono (0.69 mg%) se mantienen sobre el nivel de saturación del sistema de transporte, a diferencia de lo que ocurre en el gato. DHA no pudo detectarse en el plasma del gato ni del mono, ni en el humor acuoso del gato. Sí pudo detectarse, sin embargo, en el humor acuoso del mono, a niveles de un 3% de la concentración de ascorbato total. La cinética de la incorporación de ascorbato al ojo del gato y del mono tras la inyección intravenosa de DHA apoya la idea de que la especie molecular que el cuerpo ciliar transporta es la forma reducida, ascorbato, y no DHA. Este sería convertido intravascularmente (leucocitos y hematíes) a ascorbato, antes de incorporarse al humor acuoso

The hemogram, serum biochemistry, and electrolyte profile of the free-ranging Cayo Santiago rhesus macaques (Macaca mulatta).

Sixty-four male and 33 female free-ranging rhesus monkeys (Macaca mulatta) from one of six social groups on the island of Cayo Santiago, Puerto Rico, were surveyed to establish normal values for the hemogram and serum biochemical and electrolytes for the colony. Mean values (± 1 SD) are reported by sex for each of three age groups (2-3, 4-9 and ≥ 10 years). All adult females (≥ 4 years) were pregnant. There were significant differences for a number of variables compared to the range reported in the existing literature, and among the age and sex groups in the sampled population.

Nasal and cutaneous anatrichosomiasis in the free-ranging rhesus monkeys (Macaca mulatta) of Cayo Santiago.

One hundred and twenty-nine free-ranging rhesus monkeys on the island of Cayo Santiago were surveyed for the nematode Anatrichosoma cutaneum. The purpose of the study was to determine the prevalence of the nasal and cutaneous forms of this parasite in untreated rhesus monkeys maintained in a seminatural subtropical environment. The average prevalence of the nasal form in the sampled Cayo Santiago macaques was 23.2%. Adults were more commoly effected than yearling monkeys with 31.2% and 12.8% parasitized, respectively. Newborn infants were negative. No cases of the cutaneous form were identified. This study determined that nasal Anatrichosomiasis is common in the Cayo Santiago macaques. Further studies are necessary to establish the roles of intermediate host(s) and rhesus monkey behavior in the life cycle of this parasite in order to determine how Anatrichosomiasis has persisted for over 40 years in this colony.

A fatal epizootic of undetermined etiology in new world monkeys.

A peracute epizootic disease, strikingly characterized by profuse terminal hemorrhaging from the lungs, caused the deaths of 104 squirrel monkeys and 3 capuchin monkeys over a 22-month period. The case fatality rate was 100%. The pulmonary hemorrhaging was often accompanied by pulmonary edema and congestion, interstitial pneumonia, and hydrothorax. Additional histologic lesions included interstitial nephritis, hepatitis and hepatic necrosis, adrenalitis and adrenal necrosis, myocarditis, splenic atrophy or hypoplasia, pancreatitis and pancreatic necrosis, sialoadenitis, and encephalitis. Macaques maintained under identical conditions were clinically unaffected by the epizootic. There was an incidental relationship with contamination of feed, water, and housing facilities by excrement from feral Norway rats and cockroaches. Due to the association of the disease outbreak with abundant rodent and cockroach populations, and because the histologic features of the disease were suggestive of a viral etiology, encephalomyocarditis virus infection was implicated. However, histopathologic examinations of tissues from 68 monkeys; electron-microscopic studies on five monkeys; bacteriologic culturing; virus isolation attempts from 10 monkeys, rats, and cockroaches; and experimental inoculation studies in mice and squirrel monkeys all failed to reveal the causative agent, to provide a definitive diagnosis, or to reproduce the disease.

A five-year study of tetanus in the Cayo Santiago rhesus monkey colony: Behavioral description and epizootiology.

Tetanus is a major cause of death in the free-ranging rhesus moonkey colony on the island of Cayo Santiago, Puerto Rico. During the five-year period of observation (July 1, 1976 through June 30, 1981), the mean annual tetanus mortality rate (± 1 SD) was 1.74% (±0.15). The mean annual total mortality rate was 6.77% (±0.78). The tetanus mortality rate varied sigificantly (P < 0.005) among the six troops on the island. Clinically confirmed tetanus accounted for 24.68% of the 231 deaths which occurred on the island during the study. Although the base population increassed from 479 to 914 monkeys or 90.8% in five years, there were no significant changes in either the total or the tetanus mortality rates. The mean age of tetanus deaths was 6.9 years (±3.9) in the males and 7.1 years (±5.4) in females. The mean age-specific tetanus mortality rate increased with age. Of the 67 confirmed tetanus cases, 57 proved fatal (26 males, 31 females) for a case fatality rate of 85.1%. There was no significant sex difference in the tetanus mortality rate. No confirmed cases of neonatal tetanus were observed. Infection of juveniles and adults of both sexes occurred chiefly through septic wounds, but postpartum infection of females was also noted. The peak incidence of tetanus deaths for both sexes occurred during the mating season of the annual reproductive cycle, as a consequence of increased levels of aggression and subsequent wounding. The diagnosis of tetanus was based solely on the clinicla signs and was characterized by early behavioural abnormalities consisting of torpor, reluctance to interact with other animals, inability to prehend food, inordinate thirst, difficulty in swallowing, progressive stiffening and adduction of the pectorla limbs, bipedeal running, "kangaroo hopping," "toppling over," and pilo-erection. As the disease advanced, severely affected individuals developed the classic human triad of tetanus symptomatology:trismus (lockjaw), extensor rigidity, and opisthotonus, which progressed in most cases to status epilepticus and death from respiratory paralysis or physical exhaustion. The course of the disease in fatal cases ranged in duration from 24 hours to ten dyas. Obese monkeys with mild cases of tetanus were the most likely to recover with some taking as long as a month to return to normal condition and regain body weight. Of ten recoveries, six were female and four male. Multiple cases were observed in one adult male, indicating that previous infections do not necessarily confer immunity to future attacks. Survivous did not have demonstrable antitoxin titers to Clostridium tetani toxin, thus confirming that tetanus is a nonimmunizing disease. One half of an annual birth crop of thesus monkeys inoculated with tetanus toxoid at the age of one year had protective levels of tetanus antitoxin seven years postinoculation. However, the immunization program had no significant effect on either the total or tetanus motality rates during the study.