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Biomedical subjects

C R Abee

Publications and source records attributed to C R Abee.

At least 19 recordsLinked to original sources

Midcycle and luteal elevations of follicle stimulating hormone in squirrel monkeys (Saimiri boliviensis) during the estrous cycle.

Follicle stimulating hormone (FSH) has fundamental importance in reproductive function, but its cyclic pattern has not previously been described in the squirrel monkey, due primarily to the lack of a suitable assay. An homologous radioimmunoassay (RIA) based on recombinant cynomolgus FSH measured changes in serum FSH relative to patterns of bioactive luteinizing hormone (LH), estradiol, and progesterone during the estrous cycle. FSH was observed to have a sharp peak during the late follicular phase coincident with the LH surge and then rose again during the luteal phase. Estradiol was low except for the midcycle rise, suggesting an inhibitory relationship. The rat granulosa cell in vitro FSH bioassay confirmed high levels of this hormone. Measurement of FSH in the squirrel monkey has found a pattern different from Old World primates in the luteal phase, which may provide insight into the reproductive mechanisms of this species.

Animals↗

Use of the feed additive sodium hexametaphosphate to prevent dental calculus in squirrel monkeys (Saimiri spp.).

Dental calculus and associated periodontal disease are serious clinical problems in captive squirrel monkeys. Calculus begins to appear as early as 2 years of age, with subsequent development of periodontal disease, dental abscessation, tooth loss and other sequelae. When used as a feed additive, sodium hexametaphosphate (HMP) retards the growth of calculus on previously cleaned teeth in rhesus monkeys, lemurs, and other species. We wanted to determine whether HMP would reduce dental calculus in squirrel monkeys (Saimiri spp.) whose teeth had not been pre-cleaned. The study animals were divided into two groups. One received a standard diet; the other received an identical diet containing the HMP additive at a concentration effective in other primate and non-primate species that had received dental cleaning prior to treatment with HMP. Teeth were graded for extent of calculus formation at the start of the study and at 3 and 6 months during HMP treatment. We compared the results from the two groups both by total score per animal and according to tooth type (e.g., incisors versus incisors in test and control groups). At the end of 6 months, dental calculus did not differ significantly between the experimental groups. Therefore, we conclude that HMP is ineffective in squirrel monkeys with preexisting dental calculus.

Animal Feed↗

Elevated ovarian expression and serum concentration of alpha inhibin in the luteal phase during follicular development in the squirrel monkey (Saimiri boliviensis) compared to the human.

The goal of the present investigation was to determine in the squirrel monkey the source and pattern of inhibin, a hormone known to effect reproductive steroid levels via pituitary and ovarian mechanisms. Since this seasonally polyestrous species is known to have elevated serum levels of reproductive steroids compared to other primates, the levels of ovarian alpha subunit mRNA expression and serum total alpha inhibin, estradiol, progesterone, and luteinizing hormone were measured and compared to human levels. Expression of the alpha subunit was robust in monkey luteal tissue compared to expression in human luteal tissue. Squirrel monkey serum inhibin peaked 4 days after the luteinizing hormone surge and correlated with progesterone changes. These luteal serum levels of inhibin were greater than 12 times higher than the human levels yet bio-LH activities were less than in the human during the luteal phase. Inhibin concentrations during the nonbreeding season were generally half the levels measured in the breeding season and undetectable in ovariectomized animals. However, exogenous FSH stimulation induced a marked rise in inhibin, which correlated with an estradiol rise. In conclusion, abundant alpha inhibin subunit expression in the luteal ovary of the squirrel monkey and loss of serum delectability in ovariectomized animals indicates that the principle source of inhibin in the squirrel monkey is the ovary. Elevated serum inhibin levels during the luteal phase concurrent with ovulatory-size follicular development is unique among species studied thus far. Possible simultaneous inhibin production from both follicular and luteal tissue may be responsible for the exceptionally high inhibin levels.

Adult↗

Low oxygen inhibits but complex high-glucose medium facilitates in vitro maturation of squirrel monkey oocyte-granulosa cell complexes.

PURPOSE: The objectives of these in vitro maturation studies in primate cumulus-oocyte complexes (COCs) were to evaluate the effect of a reduced-oxygen environment and to compare medium with a high-glucose concentration to medium with pyruvate but no glucose. METHODS: COCs were retrieved from squirrel monkeys stimulated with 1 mg of follicle-stimulating hormone (FSH) for 4-6 days. Experiment 1 examined maturation after 48 hr in 5% O2/5% CO2/90% N2 compared with 5% CO2/air. The medium was CMRL-1066 containing moderate glucose (5.5 mM) supplemented with 1 mM glutamine, 0.33 mM pyruvate, 0.075 IU/ml human FSH, 5 IU/ml human chorionic gonadotropin, 75 U penicillin G/ml, and 20% fetal bovine serum. Experiment 2 in 5% CO2/air, compared P-1 medium (pyruvate and lactate but no glucose) to Waymouth's medium (27.5 mM glucose), both with identical supplements. RESULTS: Only 3 (8%) of 37 COCs matured in 5% O2, while 39 (49%) of 80 matured in ambient O2. Fourteen (22%) of 64 complexes matured in P-1 medium, compared to 47 (49%) of 96 meiosis II oocytes in Waymouth's medium (P < 0.05). CONCLUSIONS: These are the first primate studies showing detrimental effects of reduced-oxygen culture on in vitro maturation. Additionally, maturation was enhanced with complex high-glucose medium suggesting that the predominant metabolism is aerobic glycolysis.

Animals↗

Molecular genetics of spectral tuning in New World monkey color vision.

Although most New World monkeys have only one X-linked photopigment locus, many species have three polymorphic alleles at the locus. The three alleles in the squirrel monkey and capuchin have spectral peaks near 562, 550, and 535 nm, respectively, and the three alleles in the marmoset and tamarin have spectral peaks near 562, 556, and 543 nm, respectively. To determine the amino acids responsible for the spectral sensitivity differences among these pigment variants, we sequenced all exons of the three alleles in each of these four species. From the deduced amino acid sequences and the spectral peak information and from previous studies of the spectral tuning of X-linked pigments in humans and New World monkeys, we estimated that the Ala --> Ser, Ile --> Phe, Gly --> Ser, Phe --> Tyr, and Ala --> Tyr substitutions at residue positions 180, 229, 233, 277, and 285, respectively, cause spectral shifts of about 5, -2, -1, 8, and 15 nm. On the other hand, the substitutions His --> Tyr, Met --> Val or Leu, and Ala --> Tyr at positions 116, 275, and 276, respectively, have no discernible spectral tuning effect, though residues 275 and 276 are inside the transmembrane domains. Many substitutions between Val and Ile or between Val and Ala have occurred in the transmembrane domains among the New World monkey pigment variants but apparently have no effect on spectral tuning. Our study suggests that, in addition to amino acid changes involving a hydroxyl group, large changes in residue size can also cause a spectral shift in a visual pigment.

Amino Acid Substitution↗

Penile vibratory stimulation yields increased spermatozoa and accessory gland production compared with rectal electroejaculation in a neurologically intact primate (Saimiri boliviensis).

Assisted reproductive techniques require an efficient semen collection procedure in cases of ejaculatory dysfunction. Anejaculation may be of psychogenic or neurogenic origin but can be overcome with stimulatory techniques. Penile vibratory stimulation (PVS) therapy for anejaculation has recently emerged as an alternative to rectal probe electroejaculation (RPE) and more invasive testicular procedures. Comparison of the stimulatory procedures in neurologically intact subjects is not ethically possible due to the discomfort involved with electroejaculation, and comparison in spinal cord injured men may be compromised due to the intricate effects of chronic denervation on semen quality. We have previously shown the efficacy of PVS in a non-human primate, the squirrel monkey. A cross-over study design comparing semen collected by PVS and RPE was employed during the breeding season in which 15 donor males were divided into two groups. One group received PVS and the other RPE, then, three days later, treatments were reversed. Twelve of 15 animals responded to PVS (80%), all with spermatozoa in the ejaculate. Mean volume (436 +/- 90 microl), motility (80.6 +/- 4.3%), and total spermatozoa (32.8 +/- 10.2 x 10(6)) were significantly higher than in the semen after RPE. RPE resulted in ejaculation in all 15 animals with a semen volume of 205 +/- 25 microl, but fewer samples contained spermatozoa (9/15) resulting in a low total count (0.5 +/- 0.3 x 10(6)). The motility was reduced in those samples with spermatozoa (n = 9; 44.1 +/- 11.4%). Additionally, accessory gland activity was measured via the seminal vesicle and prostrate markers, fructose and citric acid, respectively. The PVS specimens had significantly more fructose (2.9 +/- 0.7 mg/ejaculate) and citric acid (0.46 +/- 0.14 mg/ejaculate) compared to RPE collected specimens (1.2 +/- 0.3 mg/ejaculate and 0.24 +/- 0.04 mg/ejaculate, respectively). In conclusion, PVS produces a much greater sperm yield and increased accessory gland secretion compared to RPE in our neurologically intact squirrel monkey model.

Animals↗

Determination of fetal biparietal diameter without the use of ultrasound in squirrel monkeys.

This study evaluated manual caliper measurement of fetal BPD in Saimiri through the abdomen of the dam (TBPD) for correlation with paired ultrasound measurements, prediction of delivery date, subspecies variation, prediction of pregnancy outcome, and correlation between postpartum BPD and TBPD. Regression analysis revealed a close relationship between TBPD measurements and those obtained by ultrasound (P < 0.001). TBPD for Saimiri boliviensis boliviensis increased from a mean of 14.8 +/- 0.3 mm for 11 weeks prepartum to a delivery week measurement of 33.2 +/- 0.2mm. Delivery-week TBPD of Saimiri boliviensis peruviensis were significantly smaller than Saimiri sciureus sciureus (P < .05). Delivery week TBPD had a correlation coefficient of 0.64 with paired post-patrum measurements. No complications were associated with the technique. Delivery date could be predicted within two weeks. TBPD is an inexpensive, safe, rapid method of approximating fetal growth during the last half of pregnancy in Saimiri.

Animals↗

Cerebrovascular amyloidosis in squirrel monkeys and rhesus monkeys: apolipoprotein E genotype.

Some neuropathological changes characteristic of aging and Alzheimer's disease (AD) in humans are present also in senescent non-human primates. The human apoE4 allele is associated with an increased risk of developing late-onset familial and sporadic AD. We found that rhesus monkeys and three subspecies of squirrel monkeys are homozygous for apoE phenotype with arginine at positions 112 and 158 as in human apoE4. However, in both species threonine replaces arginine at position 61 of human apoE. It was previously shown that arginine 61 was critical in determining apoE4 lipoprotein distribution in humans.

Alzheimer Disease↗

The squirrel monkey as an animal model of pelvic relaxation: an evaluation of a large breeding colony.

OBJECTIVE: Findings of pelvic relaxation have been reported in up to 50% of older adult female squirrel monkeys. To evaluate further the potential use of the squirrel monkey as an animal model of pelvic relaxation, we objectively observed and described the perineal findings of 160 adult females. The aim of this study was to examine the relationship of perineal findings to age and parity, factors thought to predispose women to pelvic relaxation. STUDY DESIGN: The urethra, cervix, and anterior and posterior segments of the vagina were evaluated. The degree of support loss at each site was documented. Genital measurements were obtained by previously reported methods. The findings were tested for association with elements of obstetric history, age, and subspecies. RESULTS: The females represented three subspecies and ranged from 3 to 17 years old with parities of 0 to 10. The proportion of females with normal support was inversely related to increasing parity and age. Although birth weights, frequency of dystocia at term, and requirement for cesarean section did not differ significantly between females with and without evidence of prolapse, animals with multiple sites of prolapse tended to have infants with higher birth weights. Animals without prolapse were significantly younger and less likely to have been delivered of a term infant (p < 0.001). Subspecies differences unrelated to age or parity were found for each of the genital measurements. Differences were also found between animals with normal perineal findings and those with findings of prolapse. Animals with prolapse had shorter perineal bodies (p < 0.001), greater genital hiatal ratios (p < 0.001), and wider genital hiatal measurements (p < 0.001). Females with abnormal pelvic findings were of increased parity (4.0 vs 1.6, p < 0.001) and age (9.4 vs 6.3 years, p < 0.001) compared with those normal pelvic findings. CONCLUSION: Analysis of genital prolapse in a large population of breeding squirrel monkeys demonstrated an association of loss of pelvic support with age and parity. A tendency for loss of support at multiple sites was associated with obstetric complications. These observations support continuing investigation into the nature and cause of spontaneous pelvic relaxation in this species and support the potential use of this nonhuman primate as an animal model.

Age Factors↗

Restoration of oocyte maturational competency during the nonbreeding season with follicle-stimulating hormone stimulation in squirrel monkeys (Saimiri boliviensis boliviensis).

The in vitro maturation potential of oocytes retrieved during the nonbreeding season with or without prior in vivo low-dose FSH stimulation was studied in adult squirrel monkeys (Saimiri boliviensis boliviensis). Additionally, the adequacy of various protein supplements in media used for oocyte maturation was investigated. Ovaries were removed from animals in the nonbreeding season (n = 9) with or without prior treatment with a low dose (1 mg) of FSH for four days before ovariectomy. Minimal estradiol elevation was observed in serum even with stimulation. For oocyte collection, ovaries were placed in warmed 21 mM HEPES-buffered Ham's F-10. Oocytes from unstimulated ovaries were retrieved and cultured (47 of 62 recovered) in bicarbonate-buffered Ham's F-10 medium containing 0.5% BSA as protein supplement. Negligible maturation was observed at 48 h (3 of 47; 6%), and no fertilization was seen after insemination. Immature oocytes from animals stimulated with a low dose of FSH were cultured (69 of 94 recovered). With prior FSH stimulation, oocytes placed in 0.5% BSA medium matured (13 of 24; 54%) and fertilized (7 of 21; 33%) in marked contrast to oocytes from the nonstimulated monkeys. Additionally, 20% monkey serum and 20% human follicular fluid were studied as alternative protein supplements for the FSH-pretreated oocytes; these produced similar maturation rates (10 of 22, 45%; 10 of 23, 43%, respectively) and fertilization rates (8 of 21, 38%; 6 of 21, 29%, respectively). In some cases, 2 pronuclei were observed at 16 h and 4 cells were observed at 40 h. Of those activated, 63% showed cleavage ranging from 2 to 8 cells by 96 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An immunoradiometric assay for squirrel monkey prolactin.

Determination of immunoreactive prolactin in squirrel monkeys has been hampered by the lack of specific antibodies. We investigated the adaptability of a commercially available immunoradiometric assay for human prolactin, which employs two separate monoclonal antibodies (MAb I and II) to human prolactin, to determine the presence of squirrel monkey prolactin. We found that immunoreactivity curves for prolactin in squirrel monkey pituitary homogenates and serum were parallel to human prolactin standards, suggesting that the epitopes recognized by these antibodies were common to both human and squirrel monkey prolactin. Both nonglycosylated (23 kD) and glycosylated (26 kD) forms of squirrel monkey prolactin were detected in squirrel monkey pituitary homogenates by Western blot analysis using [125I]-MAb II. Neither sheep nor rat prolactin was recognized by Western blot analysis, indicating that the assay may be specific for primate prolactins. We examined the effect of ketamine HCl, an anesthetic that has been shown to elevate serum prolactin levels in other primates, on prolactin secretion in squirrel monkeys. Serum prolactin levels increased greater than fourfold after the administration of ketamine HCl (30 mg/kg b.w., i.m.) compared with control levels. Serum prolactin levels were unaffected by anesthesia with pentobarbital sodium (15 mg/kg b.w., i.v.). This assay provides a reliable and sensitive method for determining immunoreactive squirrel monkey prolactin.

Animals↗

Mating-related estradiol fluctuations during the estrous cycle of the Bolivian squirrel monkey (Saimiri boliviensis boliviensis).

The female squirrel monkey, Saimiri boliviensis, a New World monkey, has 10-day estrous cycles during the annual breeding season. Measurements of serum estradiol (E) concentrations in females housed with males in breeding pens revealed markedly higher levels than previously reported. Additionally, females in breeding pens appeared to have two distinct patterns of serum E peaks relative to the LH surge. Serum estrogen peaks averaging 5-fold greater than levels on the preceding day were observed on the same day as the LH surge, whereas other females had only a small E rise on the day of the LH surge followed by a 6-fold E rise on the next day. The serum progesterone (P) levels in all animals were depressed for 1-2 days before the LH surge but frequently started to rise on the day of the LH surge. The effect of the presence of a breeding male was examined by studying females housed in a group pen without exposure to a breeding male. In contrast to breeding-pen patterns, relatively small E rises were found in the 10 cycles observed. To further elucidate estrus-related E rises, a limited male-access paradigm was used to isolate mating-related hormone fluctuations. Pre-mating E levels had no marked rises; however, 4 h after mating, whether on the day of the LH surge or the next day, large E rises were found. These studies indicate that the LH surge in cycling squirrel monkeys is consistently preceded by a marked P nadir and associated with relatively small E rises.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Developmental changes in ECG associated with heart rate are similar in squirrel monkey and human infants.

Interest in refining noninvasive methods of diagnosis and further characterization of squirrel monkeys (Saimiri sp.) as a model for pediatric cardiology studies led to this investigation of electrocardiogram (ECG) changes associated with changes in age and position. During a single delivery season, ECGs were performed at 1 day, 1 month, and 1 year of age. For each age group, ECGs were recorded with animals in dorsal, ventral, and right lateral recumbency. The 1-day-old group had the lowest heart rates (271 +/- 10, right lateral recumbency, mean +/- SEM) relative to the other age groups. One-year-old monkeys had heart rates of 333 +/- 18. One-month-old infants had rates significantly higher than the other two age groups (366 +/- 4). The QRS frontal-plane axis showed an age-related leftward change from 1 day (151 +/- 28 degrees) to 1 year of age (121 +/- 44 degrees) while the P-wave frontal plane axis remained nearly constant over a narrow range at all ages. The pattern of heart rate changes with age were similar to those in humans, although the ranges of absolute heart rates were markedly different. These data suggest that factors that influence maturational changes in heart rate, conduction time (as reflected by ECG intervals) and cardiac chamber size and position (inferred from axis and voltage) are similar among primates of widely variant body sizes.

Animals↗

Biochemical genetic markers of squirrel monkeys and their use for pedigree validation.

Family data for 14 biochemical genetic markers fo squirrel monkeys (genus Saimiri) were derived from 73 pedigreed progeny and both parents of each, as well as from 16 additional progeny and one parent of each. The data for each marker and the phenotypic patterns were consistent with autosomal codominant inheritance. It was concluded from the genetic marker data that the pedigree records of seven progeny were incorrect. Retrospective investigations of colony records followed by typing of animals that might possibly have been a parent enabled five of the pedigree records to be corrected. Although five of the pedigree errors were cases of mistaken paternity, the other two apparently were the consequence of infant swapping between dams shortly after birth. Because squirrel monkeys exhibit a high degree of allomaternal behavior, infant swapping between dams may occur more frequently than in many other nonhuman primate species.

Alleles↗

Distribution of chromosomal polymorphisms in three subspecies of squirrel monkeys (genus Saimiri).

The presence of nucleolar organizer regions (NORs) and C-band polymorphisms has been examined in three subspecies of squirrel monkeys, Saimiri sciureus sciureus, S. boliviensis boliviensis, and S. boliviensis peruviensis. Pericentric inversions in chromosomes 15 and 16 were also examined in the three groups. Chromosome 15 was acrocentric in S. s. sciureus and submetacentric in S.b. boliviensis and S.b. peruviensis. Chromosome 16 was acrocentric in S.s. sciureus and S.b. boliviensis while being submetacentric in S.b. peruviensis. There was a significant difference in the distribution of the C-band polymorphisms on chromosomes 5 and 14 in the three groups, as determined by Chi-square analysis, while no difference was observed in the distribution of the NOR polymorphism on chromosome 2. The NOR polymorphism and the interstitial C-band polymorphism of chromosome 14 were found in all three groups; the C-band polymorphism of chromosome 5 was found only in S.s. sciureus. Twelve pedigreed families were examined. Pedigree analyses were consistent with codominant inheritance of each polymorphism. The results of these cytogenetic studies in squirrel monkeys are pertinent to genetic management and research protocols.

Animals↗

Hypoglycemia of squirrel monkey neonates: implications for infant survival.

Neonatal deaths are a serious problem in breeding colonies of squirrel monkeys. Seriously ill neonates in our colony are always hypoglycemic on presentation. To determine normal glucose values for squirrel monkey infants of various ages, serum glucose determinations were done at 1, 3, 7, 10, 14 days and 1 month of age using a standard laboratory test for serum glucose. Glucose concentration increased from a low of 49 +/- 3 mg/dl (Mean +/- SEM) at 1 day (n = 21) to 109 +/- 4 mg/dl at 1 month of age (n = 17). Glucose values for 1, 3 and 7 day-old infants were significantly lower than 1 month-old infants (P less than .05). To provide a time-averaged indication of blood glucose, glycosylated hemoglobin (GHb) measurements were made at 1 day, 1 week, 2 weeks, 1 month, 2 months, 1 year of age and in adults (greater than 3 years of age). GHb values ranged from 2.6% +/- 0.1 for 1 day old infants (n = 13) to 4.0 +/- 0.2 for adults (n = 10) with a steady increase during the first 2 months of life. Animals 1 year of age and younger had significantly lower glycosylated hemoglobin than adults. These studies indicate that blood glucose concentration is significantly lower in squirrel monkey neonates than in older infants, juveniles and adults. Maternal rejection, trauma, and associated problems occur commonly in socially reared squirrel monkeys. The marginal hypoglycemic state of these infants places them at high risk for clinical hypoglycemia as a sequel to such perturbations.

Age Factors↗