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PubMed1988

Embryonic epsilon and gamma globin genes of a prosimian primate (Galago crassicaudatus). Nucleotide and amino acid sequences, developmental regulation and phylogenetic footprints.

Sequence analysis of epsilon and gamma genes and encoded globins and high-pressure liquid chromatography analysis of globin compositions in blood hemolysates obtained from embryos, fetuses and adults show that the prosimian primate Galago crassicaudatus expresses its epsilon and gamma genes only embryonically. Since rabbit, mouse and galago all have embryonic gamma genes but simian primates have fetal gamma genes, we conclude that gamma E evolved into gamma F in stem-simians. An elevated non-synonymous substitution rate characterizes this transition. The alignment of epsilon and gamma nucleotide sequences and the parsimoniously reconstructed evolutionary history of these sequences identify several anciently conserved cis-regulatory elements (phylogenetic footprints) important for gamma expression in primates and also cis-mutations which may have been involved in the recruitment of the gamma gene to a fetal program in simian primates.

Amino Acid Sequence↗
PubMed1989

Regulation of gonadotropin-stimulable adenylyl cyclase of the primate corpus luteum.

In an effort to understand the molecular mechanisms that control luteal function in the human and nonhuman primates, we have investigated the experimental conditions for expression of gonadotropin-induced adenylyl cyclase (AC) in membrane particles from primate corpus luteum (CL) and some of the factors modulating the enzyme activity. We also examined the usefulness of the cell-free model for studying the role of AC in the regulation of CL functions in human and nonhuman primates. Enzyme activity was dependent on guanine nucleotide and Mg ion. Dose-response curves showed that the AC activation constants for hCG was about 0.1 microgram/ml. This value did not shift after the addition of guanine nucleotide. Enzyme responsiveness to prostaglandin E2 was small and, in contrast to a number of other nonprimate species, AC from the human CL was not stimulated by catecholamines. Calcium directly inhibited responsiveness of hCG-sensitive AC; inhibition was significant at 0.5 mM CaCl2 (in the presence of 1 mM EDTA and 2 mM ATP), being 90% at 2.5 mM CaCl2. These results support the concept that Ca2+ might play a role in the regulation of gonadotropin action and life span of human CL. Changes in AC activities during luteal phase and pregnancy were similar in the CL of monkeys and humans. Thus, in both cases, maximal gonadotropin responsiveness was observed during the midluteal phase. Also, during pregnancy (term and early pregnancies), responsiveness to exogenous hCG in vitro was very low, but the enzyme was readily responsive to NaF (10 mM) and forskolin (100 microM). These activities suggest that the tissue remains functionally active during pregnancy. It is concluded that the cell-free AC system is an effective model to study the cellular mechanisms that regulate luteal function in human and nonhuman primates.

Adenylyl Cyclases↗
PubMed1992

A comparison of total body water measurements using whole-body magnetic resonance imaging versus tritium dilution in primates.

Standard techniques conventionally used to assess body composition have various drawbacks which include a requirement for specialized equipment and expertise not widely available, radiation exposure, extensive study time periods, and limited clinical utility. Anthropometric methods, which are more clinically feasible, also involve substantially greater calculation error. This study was designed to compare a newly developed whole-body magnetic resonance (MR) imaging technique with standard tritium dilution (THO) to measure total body water (TBW) in eight primates (Macaca fascicularis). Sedated primates underwent whole-body MR imaging (10-12 contiguous 50-mm slices) and TBW was computed using a previously validated program. After 5 days to allow for primate recovery and stabilization, TBW measurements were repeated using THO methodology. Linear regression analysis of TBWMRI (72.1 +/- 5.7% body wt) compared with TBWTHO (73.8 +/- 3.2% body wt) yielded a Pearson correlation of r = 0.8145, P = 0.02 with a mean squared error of 2.14. Whole-body MR imaging determination of TBW correlates well with THO, requires less time (20 min versus 24 hr), and does not expose the subject to radiation. This study suggests that whole-body MR imaging is an accurate technique for in vivo body composition analysis. As demonstrated by the body size of this investigational primate model, the technique maybe particularly applicable to the study of human infants.

Animals↗
PubMed1992

Differences in cell division and thymidine incorporation with rat and primate fibroblasts in collagen lattices.

Human and gorilla dermal fibroblasts, primate cells, suspended in a collagen lattice, do not divide for the first 3 days. In contrast, rat fibroblasts divide within 24 hr. In this study, the proliferation of rat fibroblasts were compared to primate fibroblasts. Rat fibroblasts in monolayer culture increase from 100,000 to 355,000 in 2 days, and human cells increase from 100,000 to 436,000 in the same period. An initial seeding of 100,000 rat fibroblasts suspended in collagen increased to 163,000 cells in 2 days. An initial 100,000 human fibroblasts seeded in collagen decreased to 80,000 cells in 2 days. Retarded proliferation of human and gorilla fibroblasts in collagen is unrelated to a defect in DNA synthesis. By autoradiography human fibroblasts suspended in collagen incorporate labelled thymidine. By flow cytometry analysis, the DNA concentrations of human fibroblasts suspended in collagen exhibited 41% in a 4N chromosome state, compared to 14% in monolayer culture. Nuclei of gorilla fibroblasts from collagen displayed 42% in a 4N state, compared to 19% in monolayer culture. With nuclei of rat fibroblasts from collagen, 14% were in a 4N state, compared to 9% in monolayer culture. Primate fibroblasts show a three-fold increase in the number of nuclei in a 4N state compared to rat fibroblasts suspended in collagen. After replating fibroblasts released from collagen in monolayer culture in the presence of 1 mM hydroxyurea (an inhibitor of DNA synthesis) primate fibroblasts doubled in 24 hr. Under identical conditions, rat fibroblasts showed no cell division.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Factors influencing the binding of large immune complexes to the primate erythrocyte CR1 receptor.

This study was undertaken to ascertain the relationship between the size of immune complexes and their capacity to be bound by primate erythrocytes, and to examine the role of complement in the binding of very large immune complexes to erythrocytes. Preformed bovine serum albumin-rabbit anti-bovine serum albumin immune complexes were solubilized in a fivefold antigen excess, and the supernatant fluids were subjected to differential centrifugation to select immune complexes of varying size. The size profile of immune complexes was measured on isokinetic sucrose gradients. Immune complexes were incubated with erythrocytes, and unbound immune complexes were separated from erythrocyte-bound immune complexes by centrifugation on Percoll. The results indicate that large immune complexes were bound more efficiently by primate erythrocytes than were smaller immune complexes. Depletion of complement by a variety of procedures abrogated binding of immune complexes to erythrocytes. Only the erythrocytes of primates had the capacity to bind immune complexes. Baboon or rabbit sera supported immune complex binding to baboon or human erythrocytes. In contrast, human and guinea pig sera supported immune complex binding to human erythrocytes, but these sera failed to support immune complex binding to baboon erythrocytes. These data indicate that the immune complex size and the source of serum complement are important factors which influence the binding of immune complexes to primate erythrocytes.

Adult↗
PubMed1985

Airway responses to aerosolized leukotriene D4 (LTD4) in normal and Ascaris reactor primates.

Normal and Ascaris reactor primates were compared for their bronchial pulmonary response to aerosolized leukotriene D4 (LTD4). When 10 micrograms/ml LTD4 was aerosolized (total amount delivered to endotracheal tube was 1.0 micrograms) into the lungs of 6 normal primates, a small increase in total lung resistance (RL) was noted (4.4 +/- 4.5% increase, in 19 separate challenges). However, a larger effect was seen in compliance (27.6 +/- 15.8% decrease, n = 19). Ascaris reactors (n=4) demonstrated a larger RL effect than normals with almost an identical Cdyn change (RL 36.1 +/- 27.7% increase, Cdyn 32.8 +/- 18.8% decrease n = 12). When the pharmacological blockers diphenhydramine, 0.5 mg/kg and atropine, 0.5 mg/kg were administered iv separately before LTD4 challenge, significant antagonist activity was seen. Diphenhydramine inhibited the LTD4 response in normal primates (RL 64.2 +/- 44.3% and Cdyn 50.5 +/- 40.9% n = 6) and in reactors (RL 47.8 +/- 43.1% and Cdyn 19.2 +/- 20.8% n = 4). Atropine inhibited normals (RL 100% and Cdyn 73.1 +/- 32.7% n = 2) and reactors (RL 96.3 +/- 7.7 and Cdyn 47.4 +/- 35.1% n = 3). These results indicate that the LTD agonist action is partially mediated through histamine, primarily acting on lung resistance (large airways) and, in addition, may have a reflex atropine-sensitive component. The difference between the response of normal and reactor primates to LTD4 is primarily a histamine-mediated large airway response.

Animals↗
PubMed1993

Characterization of alveolar macrophage eicosanoid production in a non-human primate model of mineral dust exposure.

The relative activation of eicosanoid production which results from the exposure of the alveolar macrophage (AM) to mineral dusts is thought to be a key factor in the pathophysiology of occupational lung disease. We compared in vitro basal and silica-stimulated production of prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) by AM from normal humans and non-human primates (Macaca nemestrina). In addition, we instilled mineral dusts directly into one lung of the non-human primate and evaluated AM eicosanoid production at two week intervals following dust instillation. Unstimulated AM from humans produce more PGE2 and TXA2 than do AM from M. nemestrina. However, in vitro exposure of AM from both species to silica dust produced a qualitatively similar increase in TXA2 production accompanied by no change in PGE2 production. Sequential analysis of AM eicosanoid production following a single bolus exposure to bituminous or anthracite coal dusts, titanium dioxide (TiO2) dust or crystalline silica showed marked variability among individual non-human primates in qualitative and quantitative aspects of dust-induced eicosanoid production. However, the rank order of potency of the different dusts (silica > anthracite > bituminous) correlated with epidemiological evidence relating the type of dust mined to the incidence of pneumoconiosis. These studies suggest that the non-human primate may serve as a model for the study of both the role of eicosanoids in the etiology of dust-induced occupational lung disease and the biochemical basis for individual variability in the response of lung cells to mineral dust exposure.

Adult↗
PubMed1988

Immunological cross-reactivity of antibodies with species chorionic gonadotropin is a critical requirement for efficacy testing of human gonadotropin vaccines in sub-human primates.

A key question in the evaluation of a contraceptive vaccine is its efficacy in the prevention of pregnancy. Primates have been employed for evaluation of the efficacy of candidate vaccines against human chorionic gonadotropin (hCG). Discrepancies have been noted between the immuno-reactive antibody titres (against hCG) determined by RIA and their ability to prevent pregnancy in test animals. To gain further information on factors involved in fertility control, other characteristics of antibodies, such as affinity for hCG, bioneutralization capacities for hCG, hLH and monkey chorionic gonadotropin, have been determined in antisera from ten bonnet monkeys (Macaca radiata) at times when they were infertile and in bleeds preceding conception. The data reported show that the most important correlate for efficacy is the bioneutralization capacity of the antibodies for the species CG; animals became pregnant when the neutralization capacity diminished to low levels (less than 45 IU/l = 5 ng/ml of hCG equivalent). The bioneutralization of heterospecies CG decreased with the increase in affinity for hCG. These findings have implications for the choice and suitability of primate species for the various candidate vaccines being developed. Vaccines inducing highly specific antibodies against hCG, and restricted in their reactivity with primate CG, may not be testable in heterospecies primate models.

Animals↗
PubMed1983

Hemolytic complement measurement in eleven species of nonhuman primates.

A microtiter system was used to measure hemolytic complement levels in serum from eleven nonhuman primate species. The species studied were Macaca mulatta (rhesus macaque), Macaca radiata (bonnet macaque), Macaca nemestrina (pig-tailed macaque), Macaca fascicularis (crab-eating macaque), Macaca speciosa (stumptailed macaque), Papio cynocephalus (yellow baboon), Papio anubis (olive baboon), Cercopithecus aethiops (African green monkey), Aotus trivirgatus (owl monkey), Ateles fusceps robustus (spider monkey), and Galago crassicaudatus panganiensis (thick-tailed galago). The optimal hemolytic complement titer of the various nonhuman primate species was found to vary with different species sources of erythrocytes and anti-erythrocyte reagents used in the assay. No single erythrocyte and anti-erythrocyte test reagent produced optimal titers for all of the primate species examined. Sera from several species was found to have high spontaneous lytic activity towards non-sensitized sheep erythrocytes which for six species (M. mulatta, M. radiata, M. speciosa, P. cynocephalus, P. anubis and A. trivirgatus) was equal to the titer for antibody sensitized erythrocytes. Evidence of alternate pathway complement activation as a possible reason for the high titer of lytic activity towards unsensitized erythrocytes could not be demonstrated for any nonhuman primate species. In one species, M. mulatta, the sensitizing activity of normal serum for sheep erythrocytes was shown to be in the IgM containing fraction obtained with gel filtration and to be absorbed by boiled sheep erythrocyte stroma which contains Forssman antigen.

Animals↗
PubMed1990

Nerve growth factor in the primate central nervous system: regional distribution and ontogeny.

An enzyme immunoassay for nerve growth factor was developed to determine the regional distribution and ontogenic change in the macaque (Macaca fascicularis) CNS. The standard curve of mouse nerve growth factor paralleled the dilution curves of extracts from the primate CNS at the adult and pre-natal stages. Furthermore, the nerve growth factor immunoreactive material comigrated with mouse nerve growth factor by means of carboxy methyl cellulose chromatography. These findings suggest that the immunoreactive material extracted from the primate CNS is mouse nerve growth factor-like molecules. At the adult stage, the highest level of nerve growth factor was in the hippocampus, with relatively high levels also in the hypothalamus, the cerebral cortex, the amygdala, the basal nucleus of Meynert, the septal nucleus, the cerebellum and the caudate nucleus. No detectable amounts were observed in the spinal cord, the substantia nigra or the dentate nucleus. In addition to the CNS, the pituitary gland contained about four times the level found in the hippocampus. At embryonic day 120, a high level of nerve growth factor already existed in the occipital cortex (80% of the level at the adult stage) and in the hippocampus (70% of the level at the adult stage). Between embryonic day 120 and the newborn stage in the occipital cortex and between embryonic day 120 and postnatal day 60 in the hippocampus, nerve growth factor levels increased about 1.7-fold, and after that, they gradually decreased until the adult stage was reached. In contrast, in the cerebellum, the level was quite high during the pre-natal period and declined to one-third at postnatal day 60. The developmental changes in nerve growth factor and choline acetyltransferase activity in the hippocampus were well correlated (r = 0.963) between embryonic day 120 and postnatal day 60. Our studies reveal that nerve growth factor is present in the primate CNS. The high level of nerve growth factor during embryonic stages and the good correlation with choline acetyltransferase activity suggest a physiological role for nerve growth factor in the development of the primate CNS.

Aging↗
PubMed1990

Compartmental origins of the striatopallidal projection in the primate.

The organization of striatopallidal projection neurons in the primate was studied by injecting horseradish peroxidase conjugated with wheat germ agglutinin and fluorescent markers (latex microspheres, Fluorogold, Diamidino Yellow or Nuclear Yellow) into the globus pallidus of 20 adult squirrel monkeys (Saimiri sciureus). Single injections of horseradish peroxidase conjugated with wheat germ agglutinin were placed so as to involve predominantly either one or both pallidal segments. In the double-tracer experiments, fluorescent tracer injections were centered in the external pallidum and deposits of horseradish peroxidase conjugated with wheat germ agglutinin were made in the internal pallidum. In control cases, injections were made in nearby parts of the internal capsule or striatum. Distributions of retrogradely labeled neurons in the striatum were analysed in relation to its striosomal architecture as demonstrated by histochemistry and immunohistochemistry. Three principal findings emerged. (1) Both the external and the internal segments of the primate pallidum receive input from both the caudate nucleus and the putamen, but different sets of striatal cells within these nuclei project to the two segments. (2) The striatopallidal projection in the primate originates mainly in the extrastriosomal matrix, although striosomes in the fields of labeling almost always contain some labeled neurons. (3) Heterogeneous groupings of striatopallidal projection neurons exist in the matrix and appear to be parts of three-dimensional projection-neuron arrays. We conclude that in the primate, separate lines of conduction lead from the striatum to the external and the internal pallidal segments, and raise the possibility that the cells of origin of these pathways form a mosaic in the extrastriosomal matrix.

Animals↗
PubMedDate not supplied

Behavioral assessment of young nonhuman primates: perceptual-cognitive development.

The Infant Primate Research Laboratory at the University of Washington utilizes a range of test procedures to study perceptual-cognitive development in nonhuman primate infants at high and low risk for poor developmental outcome. These test procedures rely on the visual preferences of infants and are employed in research with both human and animal subjects. The forced-choice preferential looking technique is based on the primate infants' preference for patterned over plain stimuli and allows the early measurement of visual acuity. The novelty paradigm is based on the preference that infants show for novel over familiar stimuli and is used to study intramodal and cross-modal recognition memory. Tests of recognition memory have shown sensitivity in detecting subtle functional alterations associated with perinatal risk factors such as teratogen exposure. The use of measures which assess early patterns of visual attention should be considered in both human and nonhuman primate studies in behavioral teratology.

Animals↗
PubMed2005

Aging and season affect plasma dehydroepiandrosterone sulfate (DHEA-S) levels in a primate.

In humans, plasma concentration of dehydroepiandrosterone sulfate (DHEA-S) declines with age and is considered as a potential predictor of longevity. DHEA-S is apparently unique to primates but few species of nonhuman primates have been studied for age-related changes in DHEA-S. In a short living primate, the grey mouse lemur (longevity 10-13 years), metabolic and physiological parameters exhibit high seasonal changes with age-related decrease in amplitude. From 8 month- to 11-year-old males (N = 175), plasma DHEA-S levels were measured either during the breeding season or during the winter sexual rest. Plasma DHEA-S levels show high significant changes according to season and age. During winter, DHEA-S levels were maintained low and constant over lifetime. During the summer breeding season, a decline of DHEA-S levels occurred after the age of 3 years and accelerated after the age of 6 years. DHEA-S level was about 30-40% of its adult value with age over 6 years, a stepwise pattern most closely resembling to human pattern. In mouse lemur, DHEA-S met the criteria for a biomarker of aging. When correlated to other age-related changes, the results give the opportunity to consider the mouse lemur as a promising primate model to study aging processes.

Aging↗
PubMed2003

Brain expansion and comparative prenatal ontogeny of the non-hominoid primate cranial base.

The basicranium is the keystone of the primate skull, and understanding its morphological interdependence on surrounding soft-tissue structures, such as the brain, can reveal important mechanisms of skull development and evolution. In particular, several extensive investigations have shown that, across extant adult primates, the degree of basicranial flexion and petrous orientation are closely linked to increases in brain size relative to cranial base length. The aim of this study was to determine if an equivalent link exists during prenatal life. Specific hypotheses tested included the idea that increases in relative endocranial size (IRE5), relative infratentorial size (RIE), and differential encephalization (IDE) determine the degree of basicranial flexion and coronal petrous reorientation during non-hominoid primate fetal development. Cross-sectional fetal samples of Alouatta caraya (n=17) and Macaca nemestrina (n=24) were imaged using high-resolution magnetic resonance imaging (hrMRI). Cranial base angles (CBA), petrous orientations (IPA), base lengths, and endocranial volumes were measured from the images. Findings for both samples showed retroflexion, or flattening, of the cranial base and coronal petrous reorientation as well as considerable increases in absolute and relative brain sizes. Although significant correlations of both IRE5 and RIE were observed against CBA and IPA, the correlation with CBA was in the opposite direction to that predicted by the hypotheses. Variations of IDE were not significantly correlated with either angle. Correlations of IPA with IRE5 and RIE appeared to support the hypotheses. However, partial coefficients computed for all significant correlations indicated that changes to the fetal non-hominoid primate cranial base were more closely related to increases in body size than the hypothesized influence of relative brain enlargement. These findings were discussed together with those from a previous study of modern human fetuses.

Alouatta↗
PubMed2004

Convergence of forelimb and hindlimb Natural Pendular Period in baboons (Papio cynocephalus) and its implication for the evolution of primate quadrupedalism.

The patterns of muscle mass distribution along the lengths of limbs may have important effects on the mechanics and energetics of quadrupedalism. Specifically, Myers and Steudel (J. Morphol. 234 (1997) 183) have shown that fore- and hindlimb Natural Pendular Periods (NPPs) may affect quadrupedal kinematics and must converge to reduce locomotor energetic costs. This study quantifies patterns of limb mass distribution in a live sample of Papio cynocephalus using limb inertial properties (mass, center of mass, mass moment of inertia, and radius of gyration). These inertial properties are calculated using a geometric modeling technique similar to that of Crompton et al. (Am. J. phys. Anthrop. 99 (1996) 547). The inertial properties in Papio are compared to those of Canis from Myers and Steudel (J. Morphol. 234 (1997) 183). The Papio sample has convergent fore- and hindlimb NPPs. Additionally, these limb NPPs are relatively large compared to those of Canis due to the relatively distally distributed limb mass in the Papio sample (relatively large limb masses, relatively distal centers of mass and radii of gyration, and relatively large limb mass moments of inertia). This relatively distal limb mass appears related to the grasping abilities of their hands and feet. Causal links are explored between limb shape adaptations for grasping hands and feet and the kinematics of primate quadrupedalism. In particular, if primates in general follow Papio's limb mass distribution pattern, then relatively large limb NPPs may lead to the relatively low stride frequencies already documented for primates. The kinematics of primate quadrupedalism appears to have been strongly influenced by both selection for grasping hands and feet and selection for reduced locomotor energetic costs.

Animals↗
PubMed2006

A comparison of cortical elastic properties in the craniofacial skeletons of three primate species and its relevance to the study of human evolution.

When a force is applied to an object, the resulting pattern of strain is a function of both the object's geometry and its elastic properties. Thus, knowledge of elastic properties in craniofacial cortical bone is indispensable for exploring the biomechanics and adaptation of primate skulls. However, elastic properties, such as density and stiffness, cannot be measured in all species, particularly extinct species known only from fossils. In order for advanced engineering techniques such as finite element analysis (FEA) to be applied to questions of primate and hominid craniofacial functional morphology, it is important to understand interspecific patterns of variation in elastic properties. We hypothesized that closely related species would have similar patterns of bone elastic properties, and that similarities with extant species should allow reasonable predictions of elastic properties in the skeletons of extinct primate species. In this study, we tested this hypothesis by measuring elastic properties in five areas of the external cortex of the baboon craniofacial skeleton using an ultrasonic technique, and by comparing the results to existing data from macaque and human crania. Results showed that cortical density, thickness, elastic and shear moduli, and anisotropy varied among areas in the baboon cranium. Similar variation had previously been found in rhesus and human crania, suggesting area-specific elastic patterns in the skulls of each species. Comparison among species showed differences, suggesting species-specific patterns. These patterns were more similar between macaques and baboons for density, maximum elastic and shear stiffness, and anisotropy than between either of these and humans. This finding demonstrates that patterns of cortical elastic properties are generally similar in closely related primate species with similar craniofacial morphology. Thus, reasonable estimates of cortical bone elastic properties should be possible for extinct species through the study of phylogenetically related and functionally similar modern forms. For example, reasonable elastic property estimates of cortical bone from fossil hominid skulls should be possible once adequate information about such properties in extant great apes is added to our current data from humans, macaques, and baboons. Such data should eventually allow FEA of craniofacial function in fossil hominids.

Animals↗
PubMed2005

Differential reactivity of anti-primate and anti-human secondary antibodies against human and monkey immunoglobulins: implications for determining the sensitivity of immunogenicity assays.

Development of immunogenicity assays for assessment of human antibodies to therapeutic proteins requires a quantitative determination of assay sensitivity. In the absence of true human positive controls, this is usually accomplished by utilizing affinity-purified antibodies from non-human primates or monoclonal antibodies. In the former case, it is generally considered that non-human primate antibodies will be recognized equally to human antibodies by secondary anti-human immunoglobulin reagents used in immunogenicity assays. We present results here demonstrating that this is not the case. In reality, anti-human immunoglobulin secondary antibodies do not recognize primate immunoglobulins as well as human immunoglobulins. As a result, the use of affinity purified primate antibodies to determine the sensitivity of an immunogenicity assay will likely result in the true sensitivity of the assay being underestimated.

Animals↗
PubMed2005

Analysis of large-scale nonhuman primate islet isolations.

AIMS: It is important to have clinically relevant large animal models, especially nonhuman primates, to improve the efficacy of islet isolation and transplantation prior to clinical trials. The aim of this study was to improve the efficacy of islet isolation by analyzing large-scale nonhuman primate islet isolations. METHODS: Sixty-one islet isolations were evaluated using nonhuman primates. An automated isolation method was scaled down for islet isolation. Islet yields of prepurification, postpurification, and postculture, purity of islets, viability of islets, and functionality with glucose stimulation test were assessed. Initially, we analyzed relationships between endpoints then analyzed additional factors for successful islet isolation. Those factors included donor characteristics, the two-layer method (TLM) of pancreas preservation, trypsin inhibition during digestion, and digestion and collection time. RESULTS: Prepurification islet yields were strongly correlated with postpurification yields and postculture yields. It weakly but significantly correlated with purity, viability, and functionality. The average prepurification yield was 16,267 IE/g with each case divided into either above-average (high-yield group) or below-average groups (low-yield group). In 8 cases, TLM and trypsin inhibition were used and all cases belonged to the high-yield group. There were no significant differences between high- and low-yield groups in terms of donor age, body weight, pancreas weight, and cold ischemic time. The high-yield group had significantly longer digestion times and shorter collection times. CONCLUSIONS: TLM, trypsin inhibition, complete digestion, and quick collections were key for successful islet isolation. Analysis of nonhuman primate islet isolation techniques provided useful information, which should help to improve clinical islet transplantation.

Animals↗