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PubMed2000

Cortical bone distribution in the femoral neck of strepsirhine primates.

The thickness of the inferior and superior cortices of the femoral neck was measured on X-rays of 181 strepsirhine primate femora representing 24 species. Neck length, neck depth and neck-shaft angle were also measured. The strength of the femoral neck in frontal bending was estimated by modeling the neck as a hollow cylinder, with neck depth as the outer diameter and cortical thickness representing the superior and inferior shell dimensions. Results indicate that the inferior cortex is always thicker than the superior cortex. The ratio of superior to inferior cortical thickness is highly variable but distinguishes two of the three locomotor groups in the sample. Vertical clingers and leapers have higher ratios (i.e., a more even distribution of cortical bone) than quadrupeds. The slow climbers tend to have the lowest ratios, although they do not differ significantly from the leapers and quadrupeds. These results do not confirm prior theoretical expectations and reported data for anthropoid primates that link greater asymmetry of the cortical shell to more stereotypical hip excursions. The ratio of superior to inferior cortical thickness is unrelated to body mass, femoral neck length, and neck-shaft angle, calling into question whether the short neck of strepsirhine primates acts as a cantilever beam in bending. On the other hand, the estimated section moduli are highly correlated with body mass and neck length, a correlation that is driven primarily by body mass. In conclusion, we believe that an alternative interpretation to the cantilever beam model is needed to explain the asymmetry in bone distribution in the femoral neck, at least in strepsirhine primates (e.g., a thicker inferior cortex is required to reinforce the strongly curved inferior surface). As in prior studies of cross-sectional geometry of long bones, we found slightly positive allometry of cortical dimensions with body mass.

Animals↗
PubMed1998

A clade of New World primates with distinctive alphoid satellite DNAs.

Centromerically located alphoid satellite DNAs are present in all primates. They typically consist of arrays of a 340-bp monomeric unit that is composed of related, but diverged, 170-bp subunits. A unique monomeric unit has recently been described: the alphoid satellite monomers of the neotropical primate Chiropotes satanas (bearded saki) are typically 539 bp in length. In addition, a number of smaller satellite sequences are present in this species. Analysis of two primates closely related to Chiropotes, Pithecia irrorata (saki) and Cacajao melanocephalus (uakari), show that they also contain unique alphoid satellites that are different from those of Chiropotes and different from one another. Southern blot and sequence analyses suggest that an alphoid satellite rearrangement(s) occurred early in the history of the tribe Pitheciini (Chiropotes, Pithecia, Cacajao) and that rearrangements are continuing to occur in this group of primates.

Animals↗
PubMed1994

Somatic gene transfer to the adult primate central nervous system: in vitro and in vivo characterization of cells genetically modified to secrete nerve growth factor.

Somatic gene transfer offers a means of delivering substances to the central nervous system (CNS) in a regionally specific, high-dose, chronic and well-tolerated manner. Studies in rats have shown that genetically modified cell grafts can prevent neuronal degeneration and promote functional recovery after injury and can improve cognitive function in aged subjects. To assess the potential utility of somatic gene transfer techniques in primate models, retroviral vectors were used to modify genetically monkey and human primary skin fibroblasts to produce and secrete human nerve growth factor (NGF). In vitro, all cell types produced NGF and sustained this production through cell growth to confluency, as determined by both Northern blot analysis and ELISA. Adult human fibroblasts produced as much NGF as did young human fibroblasts. Monkey fibroblasts genetically modified to produce NGF were then grafted to intact adult rhesus and cynomolgous monkey brains. Among nine primates that received a total of 76 grafts, surviving cells were found in all subjects up to the maximal experimental timepoint of 6 months. Cholinergic fibres from the host brain penetrated NGF-secreting grafts up to 6 months after grafting, but showed little penetration in control grafts lacking the NGF gene. Autografts survived better than allografts. These findings indicate that both human and primate fibroblasts can be transduced to produce and secrete NGF, can maintain this production whether in a growing or quiescent state and can elicit robust sprouting responses when primate fibroblasts are grafted to the adult brain. Cells genetically modified to produce trophic factors are a useful model for studying in vitro and in vivo CNS plasticity and for testing potential therapies for neurodegenerative conditions.

Animals↗
PubMed1993

Localization of inhibin/activin subunits in the testis of adult nonhuman primates and men.

The localization and distribution of inhibin/activin subunits was evaluated in the testes of three nonhuman primate species (Macaca fascicularis, M. mulatta, M. arctoides), of young (31 to 43 years) and old (60 to 85 years) men, and of men with disturbed or arrested spermatogenesis using immunohistochemical techniques (peroxidase-anti-peroxidase and alkaline-phosphatase/anti-alkaline-phosphatase technique). Specific polyclonal (anti-porcine inhibin alpha-1-32 and anti-bovine activin A) and monoclonal (anti-human inhibin alpha-1-32 and anti-human activin beta A-82-114) antisera were employed. Among all nonhuman primate species and in men, inhibin/activin subunits were present in the cytoplasm of Sertoli cells and Leydig cells but not in germ cells. No relationship could be established between the staining pattern for inhibin/activin subunits and the completeness or the stage of the spermatogenic process. The staining for the beta A-subunit in Sertoli cells appeared more intense in the testes of old men compared with that of young men. The majority of Leydig cells contained either the alpha-subunit and beta A-subunit or the beta A-subunit alone. The signal for the beta A-subunit was remarkably intense in normal and hyperplastic human Leydig cells. These observations demonstrate the presence of inhibin/activin subunits in Sertoli cells and Leydig cells of adult primates and raise the possibility that these subunits or their respective dimers (inhibin A/activin A) might subserve a paracrine/autocrine role in the adult primate testis.(ABSTRACT TRUNCATED AT 250 WORDS)

Activins↗
PubMed1986

Comparison of the primate alphaherpesviruses. I. Characterization of two herpesviruses from spider monkeys and squirrel monkeys and viral polypeptides synthesized in infected cells.

Biological and biochemical properties of two neurotropic herpesviruses of New World monkeys--Herpesvirus saimiri type 1 (HVS-1) and Herpesvirus ateles type 1 (HVA-1)--were examined and compared. HVS-1 and HVA-1 both exhibited a time course of replication similar to another primate herpesvirus, SA 8. Both viruses grew rapidly and high titers of infectious virus were readily produced. HVS-1 and HVA-1 were also able to replicate efficiently in cell lines derived from a number of primate and non-primate species. Analysis of proteins synthesized in infected cells revealed the presence of over 30 virus-specific proteins ranging from less than 30,000 to over 200,000 daltons apparent molecular weight. Both viruses specified synthesis of a major capsid polypeptide of 148,000 daltons. Pulse labeling of cells during infection demonstrated temporal differences in the kinetics of synthesis of individual viral proteins and post-translational modification of a number of viral polypeptides. Glycosylated polypeptides synthesized in HVS-1 and HVA-1 infected cells were identified which ranged from approximately 49,000 to 120,000 daltons. Structural polypeptides of HVA-1 and HVS-1 virions were identified by SDS-PAGE analysis of purified virions. Taken together with clinical data on the diseases caused by these viruses, these studies indicate that HVS-1 and HVA-1 appear similar in many respects to both the human herpes simplex viruses and alphaherpesviruses of other primates.

Animals↗
PubMed2000

Conservation of the deleted-in-azoospermia-like-1 (DAZL1) gene structure in old world monkeys points to a homologous function of DAZL1 in this primate class.

We isolated the complete deleted-in-azoospermia-like-1 (DAZL1) gene of the old world monkey Macaca fascicularis (tentatively designated as MafaDAZL1) and compared its sequence structure to that of the other DAZL1 genes isolated so far. In addition to the homologous RNA recognition motif (RRM domain), we only identified a high conservation of the Mafa-DAZL1 coding region to the mammalian DAZL1 genes (i.e. mouse: Dazl1; and human: DAZL1) and to that of Xenopus (xdazl). Only in the primates, Macaca fascicularis and human, sequences and lengths of the 5' and 3' untranslated DAZL1 gene structures (UTRs) displayed a similar conservation as their coding regions (i.e. 91-94%). Both belong to the primate class of old world monkeys evolutionarily separated 36-55 million years ago (1). The strong conservation of the complete DAZL1 gene structure in both primate species suggests a similar control and maturation pathway of DAZL1 transcripts in the germ line of old world monkeys and also indicates a homologous function of the DAZL1 RNA-binding protein in this primate class.

3' Untranslated Regions↗
PubMed2002

Differential changes in glutamate concentration in the primate prefrontal cortex during spatial delayed alternation and sensory-guided tasks.

Glutamate is a major neurotransmitter in the mammalian brain and glutamatergic neurotransmission in the frontal cortex is indicated to play important roles in cognitive operations. We previously examined changes in extracellular dopamine in the primate frontal cortex in cognitive tasks, and in this paper we extend this to glutamate. We employed, as cognitive tasks, a delayed alternation task where the animal must retain information in working memory, and a sensory-guided task in which there is no working memory requirement but there may be more sensory processing requirements. Using the in vivo microdialysis method, we examined changes in extracellular glutamate concentration in the dorsolateral, arcuate, orbitofrontal, and premotor areas of the primate frontal cortex. Compared to basal rest levels, we observed significant increases in glutamate concentration in dorsolateral and arcuate areas of the prefrontal cortex during the sensory-guided task, but did not find significant changes in any of the frontal areas examined during the delayed alternation task. When glutamate concentration was compared between the delayed alternation and sensory-guided tasks, difference was observed only in the dorsolateral prefrontal cortex, especially in the ventral lip area of the principal sulcus. The results indicate the importance of glutamate in processing sensory information but not in retaining information in working memory in the primate dorsolateral and arcuate prefrontal cortex. We also compared the concentration of glutamate and dopamine in the tasks. We found a double dissociation in the concentration of glutamate and dopamine in the dorsolateral area: there was an increase in glutamate but no change in dopamine during the sensory-guided task, whereas there was an increase in dopamine but no change in glutamate during the delayed alternation task. It is thus suggested that in the primate dorsolateral prefrontal cortex, increased glutamate tone without dopamine increase facilitates sensory-guided task performance, while increased dopamine tone without glutamate increase is beneficial for working memory task performance.

Animals↗
PubMed2004

Ancestral population sizes and species divergence times in the primate lineage on the basis of intron and BAC end sequences.

The effective sizes of ancestral populations and species divergence times of six primate species (humans, chimpanzees, gorillas, orangutans, and representatives of Old World monkeys and New World monkeys) are estimated by applying the two-species maximum likelihood (ML) method to intron sequences of 20 different loci. Examination of rate heterogeneity of nucleotide substitutions and intragenic recombination identifies five outrageous loci (ODC1, GHR, HBE, INS, and HBG). The estimated ancestral polymorphism ranges from 0.21 to 0.96% at major divergences in primate evolution. One exceptionally low polymorphism occurs when African and Asian apes diverged. However, taking into consideration the possible short generation times in primate ancestors, it is concluded that the ancestral population size in the primate lineage was no smaller than that of extant humans. Furthermore, under the assumption of 6 million years (myr) divergence between humans and chimpanzees, the divergence time of humans from gorillas, orangutans. Old World monkeys, and New World monkeys is estimated as 7.2, 18, 34, and 65 myr ago, respectively, which are generally older than traditional estimates. Beside the intron sequences, three other data sets of orthologous sequences are used between the human and the chimpanzee comparison. The ML application to these data sets including 58,156 random BAC end sequences (BES) shows that the nucleotide substitution rate is as low as 0.6-0.8 x 10(-9) per site per year and the extent of ancestral polymorphism is 0.33-0.51%. With such a low substitution rate and short generation time, the relatively high extent of polymorphism suggests a fairly large effective population size in the ancestral lineage common to humans and chimpanzees.

Animals↗
PubMedDate not supplied

Clearance of blood-borne pathogens mediated through bispecific monoclonal antibodies bound to the primate erythrocyte complement receptor.

The primate erythrocyte complement receptor facilitates both the immune adherence reaction and the immune complex clearance properties of primate erythrocytes. These phenomena have been studied for more than 40 years. However, it has only recently become apparent that these characteristics of primate erythrocytes may be useful in the generation of a therapy based on bispecific monoclonal antibodies. Our approach uses bispecific monoclonal antibody constructs (heteropolymers) that promote binding of specific target pathogens to primate erythrocytes via the complement receptor. Once bound to the erythrocytes, the pathogen-heteropolymer complex should be cleared from the circulation, phagocytosed and destroyed in the liver. Results with several prototype target pathogens in monkey models indicate it may be possible to use this technology to develop a robust and general therapy for the treatment of diseases associated with blood-borne pathogens.

Animals↗
PubMed2004

Form and function of the oblique cord (chorda obliqua) in anthropoid primates.

The oblique cord of the forearm in humans is a ligament connecting the anterolateral aspect of the ulna proximally to the posteromedial aspect of the radius distally, inserting just below the radial tuberosity. Its functional significance is uncertain, but it has been proposed that the ligament limits supination of the forearm or aids in resisting buckling failure in the curved radius. These functional explanations are unsatisfactory for bipedal humans who do not use their forelimbs in weight support. Furthermore, there are no evolutionary explanations for its presence in humans. The purpose of this study was to investigate the distribution and form of the oblique cord in non-human primates and to explore its possible functional significance and evolutionary origin in humans. Soft tissue dissections of anthropoid primates revealed the presence of an oblique cord in New and Old World monkeys and Asian apes. It was absent in all atelines. Passive manipulation of the two forearm bones in all specimens revealed that the ligament becomes most taut in pronation contrary to the proposed human condition. Isolated radii show that the oblique cord's radial insertion lacks a clear relationship with bone curvature, thus providing little support for the hypothesis of preventing buckling failure. The oblique cord's involvement in reducing bending strain in the curved radius is also unlikely. It is suggested here that the ligament may have a role in maintaining elbow stability in quadrupedal primates. Therefore, the function of the oblique cord in anthropoid primates suggests that its presence in modern humans may be a morphological and functional remnant from a quadrupedal ancestry.

Animals↗
PubMed2006

Bone regeneration using rhBMP-2 induction in hemimandibulectomy type defects of elderly sub-human primates.

Our previous work has shown that total osseous reconstruction of large discontinuity hemimandibulectomy, critical-sized defects can be achieved easily in 8-year-old Macaca fascicularis monkeys (Boyne 1996). However the literature has indicated that animal aging decreases the BMP induction of stem cells in rats and in other rodent species. It was necessarily important that the rhBMP-2 be demonstrated in non-human primates to determine if this reduction in effectiveness also existed in the higher animals phylogenetically. The purpose of this study was to operate aged non-human primates duplicating the model used in middle-aged animals to demonstrate regeneration of hemimandibulectomy defects. This age group could be extrapolated to the 80-year-old clinic patient. Six non-human primates aged 20 years were rendered edentulous posteriorly and the mandibles allowed to heal. Three months postoperatively bilateral hemimandibulectomies were performed. The defects received BMP in a collagen sponge (Helistat) using a dose level of 0.75 mg of rhBMP-2. After the manner previously reported by Boyne (1996, 1999), at the end of four months the surgical sites were exposed by mucoperiosteal flap demonstrating complete regeneration of the critical-sized defects. The animals received two dental implants in restored areas. The implants were brought into function approximately four months later, and were allowed to function for eight months in all cases. The results indicate that the regeneration of mandibular critical-sized defects by the use of rhBMP-2 in aged animals is comparable to that of the middle-aged group. This study indicates that aged non-human primates, chronologically comparable to 80-year-old humans, respond as favorably to rhBMP-2 as do the middle-aged animals. Extrapolating the results to the clinical level, one would expect that rhBMP-2 would produce a comparable result in the regeneration of large hemimandibulectomy-type defects in clinical human patients.

Aging↗
PubMed1979

Immunological comparison of proline-rich proteins from human and primate parotid secretion.

Antisera raised in response to proline-rich proteins purified from parotid secretions of man and the primate Macaca fascicularis were employed to investigate the interrelationships of these proteins by immunodiffusion, immunoelectrophoresis and the combined use of disc gel acrylamide electrophoresis with radial immunodiffusion. The major human proline-rich proteins, PRP I, PRP II, PRP III and PRP IV as well as several minor proline-rich proteins cross-react with antiserum to PRP I or PRP III. Similarly primate parotid saliva contains several components cross-reacting with antiserum directed against a purified primate proline-rich protein, MPRP. Antiserum to PRP I or PRP III cross-reacted with MPRP and primate parotid saliva protein, whereas antiserum to MPRP cross-reacted only with human parotid saliva protein and not with the isolated human proline-rich proteins. The immunological relationships of these salivary proline-rich proteins within and between species suggest their origin from a common precursor molecule.

Animals↗
PubMed1991

Cytochrome P450IID subfamily in non-human primates. Catalytical and immunological characterization.

Interindividual variations of debrisoquine metabolism was recently identified in non-human primates tested in vivo. The catalytical and immunological characterization of cytochrome P450IID subfamily was undertaken in hepatic microsomes from extensive metabolizer primates. The NADPH/O2 mediated metabolism of debrisoquine, dextromethorphan and bufuralol was similar to the kinetics reported in humans. The CuOOH mediated metabolism of bufuralol suggested that at least two enzymes are responsible for bufuralol 1'-hydroxylation. Eleven compounds were tested for their capacity to modify P450IID function in vitro. Eight competitive inhibitors of P450IID6 in man were all and exclusively competitive inhibitor of P450IID subfamily in non-human primates. Quinidine, which is the strongest competitive inhibitor in man, exhibited the higher inhibitory potency in monkey (Ki = 0.75 microM). Anti-LKM antibody against P450IID subfamily cross-reacted with two proteins of 49 and 47 kDa, and sera containing anti-LKM antibody against these two proteins inhibited dextrorphan formation in vitro. These data provide evidence for catalytical and immunological similarities between human and monkey microsomes and indicate that the primate system could be a model for enzymatic studies of P450IID.

Animals↗
PubMed1988

Persistence of the pars externa system of the anterior olfactory nucleus in a microsmatic primate, Callithrix jacchus.

The pars externa (PE) system of the anterior olfactory nucleus (AON) in a primate, Callithrix jacchus, was defined by its architecture and by its connection patterns with the main olfactory bulb (MOB) as revealed by tracing techniques. Focal, unilateral injections of wheat germ agglutinin-conjugated horseradish peroxidase into the MOB yielded ipsilaterally labelled afferent neurons in all subdivisions of the AON, with the exception of a clearly circumscribed area in the ventrolateral retrobulbar field of the basocaudal frontal lobe; in the contralateral hemisphere, this same area contained intensely stained neurons forming a horizontal flat plate of small neurons. This unique commissural connection pattern parallels the organization of the PE to MOB connection in sub-primates (Schoenfeld and Macrides, 1984, J. Comp. Neurol., 227: 121-135). Thus, despite earlier controversy (Crosby and Humphrey, 1939, J. Comp. Neurol., 71: 121-213), there appears to be a PE system in a microsmatic primate whose organization is quite similar to that in sub-primates.

Animals↗
PubMed1991

Parcellated organization in the trigeminal and dorsal column nuclei of primates.

The subdivisions of the brainstem trigeminal complex in non-primate mammals are characterized by aggregated or parcellated patterns of neural organization. The present studies used cytochrome oxidase histochemistry to test if parcellated organization patterns also occur in the brainstems of primates. The results demonstrate that a parcellated pattern of neural organization exists in the trigeminal nucleus principalis, but not in the spinal trigeminal nuclei, of macaque and squirrel monkeys. The results further suggest that parcellation in the nucleus principalis qualitatively resembles the aggregated organization in dorsal column nuclei. Taken together with previous findings from non-primates, these results indicate that central parcellation is an organizational feature of specific ascending somatosensory projections in many mammals including primates.

Animals↗
PubMed1992

Ultrastructural features of primate granule cell bodies show important differences from those of rats: axosomatic synapses, somatic spines and infolded nuclei.

Granule cells of the primate dentate gyrus were examined in the electron microscope where they displayed significantly less axosomatic synapses than granule cells in rodents. In addition, primate granule cells frequently had infolded cell nuclei and somal spines which are features that are both rare in rodents. Since the granule cell body is an important site for gamma-aminobutyric acid (GABA)ergic inhibitory control, the reduced number of axosomatic synapses in monkeys suggests that local inhibitory connections of primate granule cells are less than that of rodents. Together, these differences may indicate that the primate granule cells are physiologically more active than rat granule cells.

Animals↗
PubMed1996

An enzyme immunoassay for serum and urinary levonorgestrel in human and non-human primates.

A microtiter plate enzyme immunoassay (EIA) is reported for the measurement of levonorgestrel (LNG) in serum and urine samples of human and non-human primates, and the results are compared to data obtained by radioimmunoassay (RIA). Rabbit polyclonal antibodies were raised against the bovine serum albumin conjugate of the 3-O-carboxymethyl oxime (CMO) derivative of LNG. The enzyme label was produced by the conjugation of horseradish peroxidase to LNG at the 3-position by the same CMO bridge used for the immunogen. The assay requires 2.5 hours to perform using 2.2-azino-di-(3-ethylbenzthiazoline sulfonic acid) diammonium salt as the chromogenic substrate. Serum (100 microliters) is extracted with petroleum ether prior to assay, whereas urine samples (25 microliters) are diluted and measured directly. The sensitivity of the assay is 0.25 pg/well with a 50% displacement of label at 7.5-9.5 pg and a linear response through 250 pg/well. Minimum levels of 8.7 and 10.0 pg/ml can be detected in serum and urine samples, respectively. Changes in serum LNG concentrations were measured in women and non-human primates following LNG implantation or injection. In the non-human primate study, serum LNG concentrations began to rise rapidly following i.m. injection of LNG, with peak levels occurring on days 3 to 5, then decreasing to approximately 25-35% of peak levels for the duration of the study. Circulating concentrations of 1.86 +/- 0.18 ng/ml LNG were reached in women the first week post-insertion of Norplant implants and decreased by 50% at 7-10 days, 75% after 14-21 days, followed by a steady decrease during the next 60-70 days to constant low levels that exhibited a high individual variation. Correlation coefficients of EIA and RIA results were 0.988 for human serum, 0.926 for human urine, and 0.972 for non-human primate serum.

Adolescent↗
PubMed1987

Leishmania major: the suitability of East African nonhuman primates as animal models for cutaneous leishmaniasis.

The susceptibility of four species of East African nonhuman primates to experimental infection with Leishmania major was investigated. Four Syke's monkeys (Cercopithecus mitis), two vervet monkeys (Cercopithecus aethiops), two baboons (Papio cynocephalus), and two brown bushbabies (Galago garnettii) were each inoculated intradermally on the left eyelid, left ear, and nose with 0.1 ml of medium containing 1 x 10(7) promastigotes of a characterized L. major strain. All the nonhuman primates except the bushbabies developed erythema and conspicuous nodules on the eyelids and ears by 3 weeks PI. The nodules increased rapidly in size and ulceration was evident on the eyelids and ears by 49 days PI in the vervets, Syke's, and baboons. The aspirates were positive in culture or smears at 35, 49, 63, and 77 days PI. No parasites were observed in cultures or smears at 92, 105, 128, 147, and 161 days PI. The lesions in these animals began resolving by 84 days PI and were completely healed by 112 days PI. The exception was one baboon in which lesion healing did not start until around 147 days and was completely healed by 182 days PI. Cultures from the liver failed to demonstrate visceralization of the parasite in any of the animals throughout the 68 weeks of the experiment. Challenge with the same strain of L. major 6 months PI, corresponding to about 3 months after self cure, failed to produce infection in any of these experimental hosts. All the nonhuman primates except the bushbaby when challenged with the same strain of L. major at 12 months PI developed lesions and were positive for parasites at 14 and 28 days PI. Positive cultures were obtained from the eyelid and ear of one vervet up to 42 days PI. However, the lesion sizes in all these animals were smaller than in the initial infection and did not ulcerate. The nodules disappeared within 6 to 8 weeks as compared to 16 weeks in the initial infection. The histopathological appearance of the lesions varied from diffuse infiltration of plasma cells and lymphocytes which increased progressively to granulomata with epitheloid cells. This study shows that the vervets, Syke's, and the baboons are equally susceptible to L. major infection, while bushbabies are refractory. The vervets, Syke's, and baboons demonstrate a self-healing phenomenon within about 3 months which is comparable to that observed in humans infected with L. major. These three species of nonhuman primates are therefore considered as suitable models for drug or vaccine trials against human zoonotic cutaneous leishmaniasis.

Animals↗