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PubMed1991

A collagen-based nerve guide conduit for peripheral nerve repair: an electrophysiological study of nerve regeneration in rodents and nonhuman primates.

When a peripheral nerve is severed and left untreated, the most likely result is the formation of an endbulb neuroma; this tangled mass of disorganized nerve fibers blocks functional recovery following nerve injury. Although there are several different approaches for promoting nerve repair, which have been greatly refined over recent years, the clinical results of peripheral nerve repair remain very disappointing. In this paper we compare the results of a collagen nerve guide conduit to the more standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves in rats and nonhuman primates. In rats, we tested recovery from sciatic nerve transection and repair by 1) direct microsurgical suture, 2) 4 mm autograft, or 3) entubulation repair with collagen-based nerve guide conduits. Evoked muscle action potentials (MAP) were recorded from the gastrocnemius muscle at 4 and 12 weeks following sciatic nerve transection. At 4 weeks the repair group of direct suture demonstrated a significantly greater MAP, compared to the other surgical repair groups. However, at 12 weeks all four surgical repair groups displayed similar levels of recovery of the motor response. In six adult male Macaca fascicularis monkeys the median nerve was transected 2 cm above the wrist and repaired by either a 4 mm nerve autograft or a collagen-based nerve guide conduit leaving a 4 mm gap between nerve ends. Serial studies of motor and sensory fibers were performed by recording the evoked MAP from the abductor pollicis brevis muscle (APB) and the sensory action potential (SAP) evoked by stimulation of digital nerves (digit II), respectively, up to 760 days following surgery. Evoked muscle responses returned to normal baseline levels in all cases. Statistical analysis of the motor responses, as judged by the slope of the recovery curves, indicated a significantly more rapid rate of recovery for the nerve guide repair group. The final level of recovery of the MAP amplitudes was not significantly different between the groups. In contrast, the SAP amplitude only recovered to the low normal range and there were no statistically significant differences between the two groups in terms of sensory recovery rates. The rodent and primate studies suggest that in terms of recovery of physiological responses from target muscle and sensory nerves, entubulation repair of peripheral nerves with a collagen-based nerve guide conduit over a short nerve gap (4 mm) is as effective as a standard nerve autograft.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Morphological taxonomy of the neurons of the primate striatum.

A quantitative taxonomy of primate striatal neurons was elaborated on the basis of the morphology of Golgi-impregnated neurons. Dendritic arborizations were reconstructed from serial sections and digitized in three dimensions by means of a video computer system. Topological, metrical, and geometrical parameters were measured for each neuron. Groups of neurons were isolated by using uni- and multidimensional statistical tests. A neuronal species was defined as a group of neurons characterized quantitatively by a series of nonredundant parameters, differing statistically from other groups, and appearing as a separate cluster in principal component analysis. Four neuronal species were isolated: (1) the spiny neuronal species (96% of striatal neurons) characterized by spine-free proximal dendrites (up to 31 microns) and spine-laden distal dendrites, which are more numerous, shorter, and less spiny in the human than in the monkey, (2) the leptodendritic neuronal species (2%) characterized by a small number of long, thick, smooth, and sparsely ramified dendrites, (3) the spidery neuronal species (1%) characterized by very thick dendritic stems and a large number of varicose recurrent distal processes, and (4) the microneuronal species (1%) characterized by numerous short, thin, and beaded axonlike processes. All striatal neurons give off a local axonal arborization. The size and shape of cell bodies were analyzed quantitatively in Golgi material and in materials treated for Nissl-staining, immunohistochemical demonstration of parvalbumin and histochemical demonstration of acetylcholinesterase. Only three types were distinguishable: small, round cell bodies corresponding to either spiny neurons or microneurons, medium-size elongated cell bodies, which were parvalbumin-immunoreactive and corresponded to leptodendritic neurons, and large round cell bodies, which were acetylcholinesterase-positive and corresponded to spidery neurons. Thorough analysis of previously elaborated classifications revealed that spidery neurons do not exist in rats and cats and that large cholinergic neurons in these species correspond to leptodendritic neurons. From this, it can be assumed that the dendritic domain of striatal cholinergic neurons is considerably smaller in primates than in other species. Computer simulations based on both the frequency of each neuronal species and their three-dimensional dendritic morphology revealed that the striatum consists of two intertwined dendritic lattices: a fine-grain lattice (300-600 microns) formed by the dendritic arborizations of spiny, spidery, and microneurons, and a large-grain lattice (1,200 microns) formed by the dendritic arborizations of leptodendritic neurons. This suggests that cortical information can be processed in the striatum through two different systems: a fine-grain system that would conserve the precision of the cortical input, and a large-grain system that would blur it.

Animals↗
PubMed1995

Variation and evolution of mammalian corticospinal somata with special reference to primates.

The morphology of the somata originating the corticospinal tract was examined in 24 species of mammals to identify commonalities and major sources of variation among the different species. Horseradish peroxidase was applied to a hemisection of the spinal cord at the C1-C2 junction. After tetramethylbenzidine processing, the labeled somata throughout the cerebral cortex were plotted and counted. Then, 23 morphological characteristics of the corticospinal somata were examined, including their number, size, and density across the cortical surface. The results show that morphological characteristics of corticospinal somata are closely related to an animal's body, brain, and cerebral cortex size. That is, mammals with large neocortical surfaces tend to have larger as well as more corticospinal somata; mammals with large bodies tend to have corticospinal somata that are less densely distributed. Moreover, the probable increase in the ratio of local noncorticospinal somata to corticospinal somata implies that the evolution of the corticospinal tract was accomplished by an increase in "support" or "server" cells as well as an increase in the size of the tract itself. The results also show that several characteristics are reliably related to an animal's taxonomic classification and hence its ancestry. Comparisons among three mammalian lineages indicate that some characteristics may have changed uniquely in the anthropoid primate lineage, and thus, presumably, in the human lineage. The results suggest that if morphological characteristics of the corticospinal tract important in the evolution of the specialized motor abilities in anthropoid primates are sought, then examination of the role of changes in soma diameter, rostral (motor)/caudal (sensory) ratios of density, concentration, surface density, and volume density may be more instructive than examination of the total number of corticospinal neurons alone.

Animals↗
PubMed2005

Social withdrawal behaviors in nonhuman primates and changes in neuroendocrine and monoamine concentrations during a separation paradigm.

This study investigated relationships between withdrawal behaviors in rhesus macaques and changes in monoamine metabolite and endocrine concentrations during repeated psychosocial stress. Rhesus monkeys (N = 71) experienced maternal separation in which four separations took place during four consecutive weeks. Behavioral observations were made, as well as plasma concentrations of cortisol and cerebrospinal fluid concentrations of the serotonin, dopamine, and norepinephrine metabolites were obtained. Animals were assigned to high, moderate, and low withdrawal groups, defined using baseline durations of withdrawal behaviors. Highly withdrawn animals showed less reduction than nonwithdrawn animals in serotonin metabolite concentrations over repeated separations. Highly withdrawn macaques also failed to significantly reduce cortisol concentrations across separation weeks. More adaptation in central serotonin functioning and cortisol concentrations was seen in nonwithdrawn primates than in highly withdrawn primates; these findings have implications for increased risk of developing anxiety disorders in highly inhibited children.

Animals↗
PubMed2004

Gustatory responsiveness to monosodium glutamate and sodium chloride in four species of nonhuman primates.

The taste responsiveness of six squirrel monkeys, five pigtail macaques, four olive baboons and four spider monkeys to monsodium glutamate (MSG) and to sodium chloride was assessed in two-bottle preference tests of brief duration (2 min). When given the choice between tap water and defined concentrations of the two tastants dissolved in tap water, the animals were found to significantly discriminate concentrations of MSG as low as 2 mM (spider monkeys and olive baboons), 50 mM (pigtail macaques) and 300 mM (squirrel monkeys) from the solvent. With sodium chloride, taste preference thresholds were found to be 1 mM (spider monkeys), 20 mM (pigtail macaques), 50 mM (olive baboons), and 200 mM (squirrel monkeys), respectively. Across-species comparisons of the degree of preference for MSG and sodium chloride displayed by the four primate species showed the same order of spider monkeys>olive baboons>pigtail macaques>squirrel monkeys. When presented with equimolar concentrations of different tastants, all four species preferred sucrose as well as a mixture of sucrose and sodium chloride over MSG, and--at least at one concentration--they preferred MSG over sodium chloride. The results support the assertion that the taste responsiveness of the four primate species to MSG and sodium chloride might reflect an evolutionary adaptation to their respective dietary habits.

Animals↗
PubMed1982

A model for comparison of masticatory effectiveness in primates.

A model is presented to express how effectively animals increase the exposed surface area of their food by chewing. It includes a coefficient of masticatory effectiveness (E) the value of which increases with effectiveness of exposing new food surface area with each chew. Humans and other species of primates differ significantly in their values of E; among the nonhuman primates studied, Lemur catta has a higher coefficient than Lemur fulvus, and both have higher coefficients than either Varecia variegatus or Galago crassicaudatus argentatus. The differences among the coefficients of these prosimians are correlated with variations in specific features of the molar morphology. Of six lower molar shearing crests considered, the relative length of the postmetacristid correlates most highly with the coefficient of masticatory effectiveness for the prosimian species. Also, among comparable-sized prosimians, E correlates significantly with the absolute postmetacristid length. Both these findings indicate that the relative size of molar shearing crests is related significantly to how effectively an animal chews its food. These are also implications for an adaptation to a high-fiber diet.

Analysis of Variance↗
PubMed1997

Transduction of hematopoietic stem cells in humans and in nonhuman primates.

Primitive hematopoietic progenitor and stem cells have been pursued as highly desirable targets for genetic therapy. Retroviral vectors have been used for the majority of preclinical and clinical studies directed at these cells; however, both preclinical and early clinical studies indicate that the gene transfer efficiency of the current generation of vectors using known transduction conditions into primate and human repopulating stem cells is too low to be of clinical utility in most situations. In this presentation I will summarize the status of our completed and ongoing clinical genetic marking trials, and describe our efforts in the laboratory and use of primate transplantation models to improve on these results.

Animals↗
PubMed2001

Synthesis and purification of 3-hydroxykynurenine-O-beta-glucoside, a primate lens ultraviolet filter, and its application in a two-step assay for beta-glucosidase activity.

3-Hydroxykynurenine-3-O-beta-glucoside (3-HKG) functions in the primate lens as a filter of 295- 400-nm light, thereby protecting the retina from damaging UV radiation. Although extensive studies have been conducted to determine the functional role of 3-HKG in the primate lens, an efficient method for its synthesis and purification has yet to be developed. Several procedures have been reported for the synthesis of 3-HKG; however, these procedures either result in low yields or require numerous sequential reactions and purification steps. In this study, we report a two-step synthesis of 3-HKG with a one-step purification and a two- to eightfold increase in yield over previously reported methods. Additionally, an assay was developed to confirm the presence of a beta-glycosidic linkage in the purified reaction product and we propose a method by which 3-HKG can be used as a general probe of beta-glucosidase activity. The assay consists of adding glucose oxidase to the 3-HKG/glucosidase solution and then allowing the hydrogen peroxide, generated from the interaction of glucose with glucose oxidase, to oxidize 3-hydroxykynurenine to xanthomattin (XAN) and 4,6-dihydroxyquinolinequinone carboxylic acid (DHQCA). Both XAN and DHQCA absorb strongly between 400 and 500 nm and the color change of the solution can be seen by eye. In addition, XAN fluoresces in the visible region with lambda(max) = 527 nm.

Animals↗
PubMed1995

Polymorphic tandem repeats in dopamine D4 receptor are spread over primate species.

The human dopamine D4 receptor has polymorphic tandem repeats in the third cytoplasmic loop. However, these repeats are not present in the rat counterpart. To determine whether the tandem repeats are specific to humans or not, we analyzed genomic DNA sequences for the D4 receptor of six primate species (human, chimpanzee, gorilla, orangutan, macaque, marmoset). Sequencing data revealed that all primates have the 48-bp tandem repeats in the D4 receptor gene. This finding suggests that these repeats originated before the separation of the New World monkey lineage from the Old World monkey and ape-human lineages.

Amino Acid Sequence↗
PubMed1994

Evolution of the chAB4 multisequence family in primates.

Approximately 50 members of the primate-specific multisequence family chAB4 are located as clusters at eight different chromosomal loci within the human genome. The whole cloned region of chAB4 represents a single-copy or low-copy sequence in all nonhuman primates tested, with the exception of the chimpanzee, for which we found chAB4 copy numbers similar to those in the human. An Alu element was inserted into chAB4 after the divergence of the Old World monkeys from the hominoids but before chAB4 was amplified. The first amplification step could be dated after the great apes and the human diverged from the Old World monkeys. We have evidence that neither the copy numbers nor the chromosomal locations remained stable after this initial step and that gross alterations in the relative copy numbers of individual family members occurred even after the divergence of the human and the chimpanzee. Taken together, our data suggest that chAB4, in an evolutionary sense, is an unusually unstable sequence family.

Animals↗
PubMedDate not supplied

Wasatchian-Bridgerian (Eocene) paleoecology of the western interior of North America: changing paleoenvironments and taxonomic composition of omomyid (Tarsiiformes) primates.

Many changes in mammalian faunas occurred across the early (Wasatchian) to middle (Bridgerian) Eocene boundary as documented in the fossil record from the Western Interior of North America. One of the more striking changes took place within the tarsiiform primate family Omomyidae. In the early Eocene, omomyids were dominated, both in abundance and diversity, by the subfamily Anaptomorphinae. In the middle Eocene, the subfamily Omomyinae dominated in abundance, while both subfamilies were nearly equally diverse. Examination of a series of paleoecological indicators including leaf-margin analysis, cenogram analysis, ecological diversity analysis of trophic structure, the distribution and development of ancient soil horizons (paleosols), and the distribution of lacustrine and fluvial facies in the Bighorn and southern Green River basins of Wyoming reveals factors that may have influenced the composition of omomyid primates. Subtle but important changes occurred in paleoclimates with mean annual temperatures reaching Cenozoic maximums at the end of the Wasatchian into the early Bridgerian. Both land mammal ages were typified by subtropical, closed forested conditions, but the Bridgerian was probably more humid and wetter than the Wasatchian. Paleohabitats most commonly sampled in the Wasatchian of the Bighorn Basin are proximal and distal floodplains, while those of the Bridgerian in the southern Green River Basin are lake margins and proximal floodplains. Changes in paleoclimate may have triggered a wave of omomyine immigration near the end of the Wasatchian with omomyines entering into habitats previously occupied by anaptomorphines. Lake margin and proximal floodplain habitats are those most commonly occupied by omomyines in the Bridgerian with anaptomorphines being more common in basin margin and distal floodplain areas not commonly sampled. Omomyine immigration and sampling of differing paleohabitats are two possible explanations for the changes documented in omomyid diversity and abundance.

Animals↗
PubMed2002

Oligocene sivaladapid primate from the Bugti Hills (Balochistan, Pakistan) bridges the gap between Eocene and Miocene adapiform communities in Southern Asia.

A new species of Guangxilemur (Sivaladapidae, Adapiformes) is described from the early Oligocene Chitarwata Formation (Bugti Member) of the Bugti Hills, Sulaiman geological Province, Balochistan, Pakistan. Guangxilemur singsilai n. sp. provides further diagnostic morphological characters from its newly described upper and lower dentitions, confirming its intermediate phylogenetic position between Eocene and Miocene Asian sivaladapid adapiforms. G. singsilai possesses moderately developed shearing and puncturing molar features and maintains lingual cusps on upper molars as in Eocene hoanghoniines; in contrast, it possesses a typical molariform P(4) as in Miocene sivaladapines. The important paleogeographic changes that have affected South Asia during the Tertiary (related to the collision between the Indian and Eurasian Plates) have played a critical role in reforming circulation and climatic differentiation. The presence in Pakistan of an unique and well-diversified Oligocene primate fauna, clearly demonstrates that South Asia maintained favourable environmental conditions during the middle Caenozoic global climatic deterioration that coincides with drastic changes in faunal structure on the whole Holarctic Province, including the extinction of adapiform primates.

Animals↗
PubMed2002

A quantitative morphometric comparative analysis of the primate temporal lobe.

Given their importance in language comprehension, the human temporal lobes and/or some of their component structures might be expected to be larger than allometric predictions for a nonhuman anthropoid brain of human size. Whole brain, T1-weighted MRI scans were collected from 44 living anthropoid primates spanning 11 species. Easyvision software (Philips Medical Systems, The Netherlands) was used to measure the volume of the entire brain, the temporal lobes, the superior temporal gyri, and the temporal lobe white matter. The surface areas of both the entire temporal lobe and the superior temporal gyrus were also measured, as was temporal cortical gyrification. Allometric regressions of temporal lobe structures on brain volume consistently showed apes and monkeys to scale along different trajectories, with the monkeys typically lying at a higher elevation than the apes. Within the temporal lobe, overall volume, surface area, and white matter volume were significantly larger in humans than predicted by the ape regression lines. The largest departure from allometry in humans was for the temporal lobe white matter volume which, in addition to being significantly larger than predicted for brain size, was also significantly larger than predicted for temporal lobe volume. Among the nonhuman primate sample, Cebus have small temporal lobes for their brain size, and Macaca and Papio have large superior temporal gyri for their brain size. The observed departures from allometry might reflect neurobiological adaptations supporting species-specific communication in both humans and old world monkeys.

Anatomy, Comparative↗
PubMed2002

Notharctine primates (Adapiformes) from the early to middle Eocene (Wasatchian-Bridgerian) of Wyoming: transitional species and the origins of Notharctus and Smilodectes.

Notharctine adapiform primates are an abundant element of early (Wasatchian) and middle (Bridgerian) Eocene faunal assemblages from the western interior of North America. Early Eocene notharctine samples are dominated by Cantius with Pelycodus and Copelemur being much rarer and more restricted in their geographic distribution. Cantius is replaced in the middle Eocene by Notharctus and Smilodectes, both of which are common but less widespread, being best known from southwestern Wyoming. The origin of these two middle Eocene taxa has not been well understood, due to a lack of transitional Wasatchian-Bridgerian notharctine faunal samples or because known samples had not been adequately studied. Field work at South Pass in the Greater Green River Basin has produced a relatively large sample of earliest Bridgerian notharctines. Combining this sample with a large, but previously under-studied, sample of notharctines from the latest Wasatchian and earliest Bridgerian in the Wind River Basin has clarified the relationships among Notharctus,Smilodectes, and earlier occurring notharctines. Notharctus first appears in the latest Wasatchian (Wa7), represented by N. venticolus. Phylogenetic analysis supports a Notharctus clade that shares sister taxon status with Cantius nunienus and indicates that Notharctus arose through bifurcation of the lineage containing the last common ancestor of C. nunienus and Notharctus. The origins of Smilodectes are less clear. Phylogenetic analysis supports a clade consisting of Smilodectes and Copelemur, but the origins of both taxa are not established as yet. North American notharctines are typified by relatively low taxonomic diversity, but relatively high abundance and high dental morphological variation (disparity). These attributes are opposite to those of North American omomyids, reflecting differences in ecomorphospace between these two primate radiations.

Adaptation, Physiological↗
PubMed2001

Molecular evolution of aerobic energy metabolism in primates.

As part of our goal to reconstruct human evolution at the DNA level, we have been examining changes in the biochemical machinery for aerobic energy metabolism. We find that protein subunits of two of the electron transfer complexes, complex III and complex IV, and cytochrome c, the protein carrier that connects them, have all undergone a period of rapid protein evolution in the anthropoid lineage that ultimately led to humans. Indeed, subunit IV of cytochrome c oxidase (COX; complex IV) provides one of the best examples of positively selected changes of any protein studied. The rate of subunit IV evolution accelerated in our catarrhine ancestors in the period between 40 to 18 million years ago and then decelerated in the descendant hominid lineages, a pattern of rate changes indicative of positive selection of adaptive changes followed by purifying selection acting against further changes. Besides clear evidence that adaptive evolution occurred for cytochrome c and subunits of complexes III (e.g., cytochrome c(1)) and IV (e.g., COX2 and COX4), modest rate accelerations in the lineage that led to humans are seen for other subunits of both complexes. In addition the contractile muscle-specific isoform of COX subunit VIII became a pseudogene in an anthropoid ancestor of humans but appears to be a functional gene in the nonanthropoid primates. These changes in the aerobic energy complexes coincide with the expansion of the energy-dependent neocortex during the emergence of the higher primates. Discovering the biochemical adaptations suggested by molecular evolutionary analysis will be an exciting challenge.

Animals↗
PubMed1999

Mutations of respiratory syncytial virus attachment glycoprotein G associated with resistance to neutralization by primate polyclonal antibodies.

The respiratory syncytial (RS) virus attachment glycoprotein G is a type II transmembrane glycoprotein and an important target of the host immune response. Antigenic variability of the G protein is postulated to contribute to the ability of the virus to evade established immune responses. A glycoprotein G monospecific polyclonal antiserum from a nonhuman primate was used to select for an antibody resistant RS virus. The mutant virus was resistant to neutralization by the selecting antiserum and by the sera from three other G-protein immunized primates. G-protein amino acid changes were found at residues 61 (Phe to Leu), 174 (Ser to Cys), and 183 (Trp to Leu). Thus the mutant protein had amino acid changes in the transmembrane domain (61) and the central ectodomain (174 and 183). The change at amino acid 174 resulted in five rather than the usual four Cys found in the conserved central region of the ectodomain. These data demonstrate that an RS virus with resistance to neutralization by polyclonal antibodies can be selected readily in cell culture. In addition, only a limited number of amino acid changes is required to produce the resistant phenotype.

Amino Acid Sequence↗
PubMed2000

Expression and coreceptor function of APJ for primate immunodeficiency viruses.

APJ is a seven transmembrane domain G-protein-coupled receptor that functions as a coreceptor for some primate immunodeficiency virus strains. The in vivo significance of APJ coreceptor function remains to be elucidated, however, due to the lack of an antibody that can be used to assess APJ expression, and because of the absence of an antibody or ligand that can block APJ coreceptor activity. Therefore, we produced a specific monoclonal antibody (MAb 856) to APJ and found that it detected this receptor in FACS, immunofluorescence, and immunohistochemistry studies. MAb 856 also recognized APJ by Western blot, enabling us to determine that APJ is N-glycosylated. Using this antibody, we correlated APJ expression with coreceptor activity and found that APJ had coreceptor function even at low levels of expression. However, we found that APJ could not be detected by FACS analysis on cell lines commonly used to propagate primate lentiviruses, nor was it expressed on human PBMC cultured under a variety of conditions. We also found that some viral envelope proteins could mediate fusion with APJ-positive, CD4-negative cells, provided that CD4 was added in trans. These findings indicate that in some situations APJ use could render primary cell types susceptible to virus infection, although we have not found any evidence that this occurs. Finally, the peptide ligand for APJ, apelin-13, efficiently blocked APJ coreceptor activity.

Adipokines↗
PubMed2000

Species-specific TT viruses in humans and nonhuman primates and their phylogenetic relatedness.

By means of polymerase chain reaction with a primer pair (NG133-NG147) deduced from the untranslated region (UTR) of TT virus (TTV), TTVs with markedly distinct genomic lengths were recovered from sera of humans and nonhuman primates, and their entire nucleotide sequences were determined. A human TTV [TGP96 of 2908 nucleotides (nt)] was obtained that was about 900 nt shorter than heretofore reported TTVs (3787-3853 nt). Likewise, TTVs of chimpanzee occurred in two distinct genomic sizes [Pt-TTV6 (3690 nt) and Pt-TTV8-II (2785 nt)]. Two TTVs of Japanese macaque [Mf-TTV3 (3798 nt) and Mf-TTV9 (3763 nt)] were comparable in genomic length, but only 55% similar in sequence. These five human and nonhuman primate TTVs, along with TTVs of tamarin [So-TTV2 (3371 nt)] and douroucouli [At-TTV3 (3718 nt)], were compared over the entire nucleotide sequence. Although the seven TTVs were only < or = 55% similar, they share a common genomic organization with two open reading frames (ORFs), designated ORF1 (654-735 amino acids) and ORF2 (91-152 amino acids). The N-terminal sequences of ORF1 proteins were rich in arginine, and sequence motifs necessary for transcription and replication were conserved among them all. Like the human prototype TTV (TA278), all seven TTVs from various animals possessed in common two 15-nt sequences (CGAATGGCTGAGTTT and AGGGGCAATTCGGGC) in the UTR that were covered by NG133 and NG147, respectively. These primers would be instrumental in research on TTVs in previously unexamined species for defining their virological characteristics and evolutionary relationships.

Amino Acid Sequence↗