Correlation between gene expression and morphological alterations in baboon carotid after balloon dilatation injury.
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Treatment for fibroproliferative restenosis after angioplasty and endovascular surgery is an unmet medical need. Rational therapy and drug design still lack the very basic knowledge about the underlying biological processes leading to pathological changes in the vessel wall. We have developed a primate model for vascular response to denudation-overstretch injury of baboon carotid artery. With this model, we have investigated the time course of vascular expression of 41,000 human cDNA clones and correlated these changes with carotid histology and function. Analysis revealed 20,788 differentially regulated cDNA clones. After high stringency data selection, the most prominently regulated 1629 cDNA clones representing 1510 genes of known function were clustered. Genes corresponding to functional and anatomical alterations in the injured carotid wall were further aligned into functional groups according to Gene Ontology classification. The observed expression patterns faithfully reflected the functional and anatomical alterations observed in the vascular wall in response to injury. The analysis presents a tentative model for genomic response to balloon catheter injury and a road map to identify time-related genomic alterations in human vascular specimens. (+info)
Specialization in pyramidal cell structure in the sensory-motor cortex of the Chacma baboon (Papio ursinus) with comparative notes on macaque and vervet monkeys.
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The systematic study of pyramidal cell structure has revealed new insights into specialization of the phenotype in the primate cerebral cortex. Regional specialization in the neuronal phenotype may influence patterns of connectivity and the computational abilities of the circuits they compose. The comparative study of pyramidal cells in homologous cortical areas is beginning to yield data on the evolution and development of such specialized circuitry in the primate cerebral cortex. Recently, we have focused our efforts on sensory-motor cortex. Based on our intracellular injection methodology, we have demonstrated a progressive increase in the size of, the branching structure in, and the spine density of the basal dendritic trees of pyramidal cells through somatosensory areas 3b, 1, 2, 5, and 7 in the macaque and vervet monkeys. In addition, we have shown that pyramidal cells in premotor area 6 are larger, more branched, and more spinous than those in the primary motor cortex (MI or area 4) in the macaque monkey, vervet monkey, and baboon. Here we expand the basis for comparison by studying the basal dendritic trees of layer III pyramidal cells in these same sensory-motor areas in the chacma baboon. The baboon was selected because it has a larger cerebral cortex than either the macaque or vervet monkeys; motor cortex has expanded disproportionately in these three species; and motor cortex in the baboon reportedly has differentiated to include a new cortical area not present in either the macaque or vervet monkeys. We found, as in monkeys, a progressive increase in the morphological complexity of pyramidal cells through areas 3b, 5, and 7, as well as from area 4 to area 6, suggesting that areal specialization in microcircuitry was likely to be present in a common ancestor of primates. In addition, we found subtle differences in the extent of the interareal differences in pyramidal cell structure between homologous cortical areas in the three species. (+info)
Complete nucleotide sequence of polyomavirus SA12.
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The Polyomaviridae have small icosahedral virions that contain a genome of approximately 5,000 bp of circular double-stranded DNA. Polyomaviruses infect hosts ranging from humans to birds, and some members of this family induce tumors in test animals or in their natural hosts. We report the complete nucleotide sequence of simian agent 12 (SA12), whose natural host is thought to be Papio ursinus, the chacma baboon. The 5,230-bp genome has a genetic organization typical of polyomaviruses. Sequences encoding large T antigen, small t antigen, agnoprotein, and the viral capsid proteins VP1, VP2, and VP3 are present in the expected locations. We show that, like its close relative simian virus 40 (SV40), SA12 expresses microRNAs that are encoded by the late DNA strand overlapping the 3' end of large T antigen coding sequences. Based on sequence comparisons, SA12 is most closely related to BK virus (BKV), a human polyomavirus. We have developed a real-time PCR test that distinguishes SA12 from BKV and the other closely related polyomaviruses JC virus and SV40. The close relationship between SA12 and BKV raises the possibility that these viruses circulate between human and baboon hosts. (+info)
Specializations of the granular prefrontal cortex of primates: implications for cognitive processing.
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The biological underpinnings of human intelligence remain enigmatic. There remains the greatest confusion and controversy regarding mechanisms that enable humans to conceptualize, plan, and prioritize, and why they are set apart from other animals in their cognitive abilities. Here we demonstrate that the basic neuronal building block of the cerebral cortex, the pyramidal cell, is characterized by marked differences in structure among primate species. Moreover, comparison of the complexity of neuron structure with the size of the cortical area/region in which the cells are located revealed that trends in the granular prefrontal cortex (gPFC) were dramatically different to those in visual cortex. More specifically, pyramidal cells in the gPFC of humans had a disproportionately high number of spines. As neuron structure determines both its biophysical properties and connectivity, differences in the complexity in dendritic structure observed here endow neurons with different computational abilities. Furthermore, cortical circuits composed of neurons with distinguishable morphologies will likely be characterized by different functional capabilities. We propose that 1. circuitry in V1, V2, and gPFC within any given species differs in its functional capabilities and 2. there are dramatic differences in the functional capabilities of gPFC circuitry in different species, which are central to the different cognitive styles of primates. In particular, the highly branched, spinous neurons in the human gPFC may be a key component of human intelligence. (+info)
Anti-L-selectin antibody therapy does not worsen the postseptic course in a baboon model.
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INTRODUCTION: Anti-adhesion molecule therapy prevents leukocytes from extravasating. During exaggerated inflammation, this effect is wanted; however, during infection, blocking diapedesis may be detrimental. In this study, therefore, the potential risks of anti-L-selectin antibody therapy were evaluated in a primate model of sepsis. METHODS: Sixteen baboons were anesthetized and randomized into two groups. The experimental group received 2 mg/kg of the anti-L-selectin antibody HuDREG-55 and the control group received Ringer's solution prior to the onset of a 2 h infusion of Escherichia coli (1-2 x 10(9) colony forming units (CFU)/kg body weight). Serial blood samples were drawn over a 72 h period for the measurement of tumour necrosis factor-alpha, IL-6 and polymorphonuclear elastase. In addition, blood gas analysis, hematology and routine clinical chemistry were determined to monitor cardiovascular status, tissue perfusion and organ function. RESULTS: The three-day mortality rate and the mean survival time after E. coli-induced sepsis were similar in the two groups. The bacterial blood CFU levels were significantly higher in the placebo group than in the anti-L-selectin group. Other parameters measured throughout the 72 h experimental period, including the cardiovascular, immunologic, and hematologic responses as well as indicators of organ function and tissue perfusion, were similar in the two groups, with the exception of serum creatinine and mean arterial pressure at 32 h after E. coli challenge. CONCLUSION: Anti-L-selectin therapy did not adversely affect survival, promote organ dysfunction or result in major side effects in the baboon sepsis model. Additionally, as anti-L-selectin therapy improved the bacterial clearance rate, it appears that this therapy is not detrimental during sepsis. This is in contrast to previous studies using the baboon model, in which antibody therapy used to block CD18 increased mortality. (+info)
Soluble and insoluble signals and the induction of bone formation: molecular therapeutics recapitulating development.
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The osteogenic molecular signals of the transforming growth factor-beta (TGF-beta) superfamily, the bone morphogenetic/osteogenic proteins (BMPs/OPs) and uniquely in primates the TGF-beta isoforms per se, pleiotropic members of the TGF-beta supergene family, induce de novo endochondral bone formation as a recapitulation of embryonic development. Naturally derived BMPs/OPs and gamma-irradiated human recombinant osteogenic protein-1 (hOP-1) delivered by allogeneic and xenogeneic insoluble collagenous matrices initiate de novo bone induction in heterotopic and orthotopic sites of the primate Papio ursinus, culminating in complete calvarial regeneration by day 90 and maintaining the regenerated structures by day 365. The induction of bone by hOP-1 in P. ursinus develops as a mosaic structure with distinct spatial and temporal patterns of gene expression of members of the TGF-beta superfamily that singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis. The temporal and spatial expressions of TGF-beta1 mRNA indicate a specific temporal transcriptional window during which expression of TGF-beta1 is mandatory for successful and optimal osteogenesis. Highly purified naturally derived bovine BMPs/OPs and hOP-1 delivered by human collagenous bone matrices and porous hydroxyapatite, respectively, induce bone formation in mandibular defects of human patients. By using healthy body sites as bioreactors it is possible to recapitulate embryonic developments by inducing selected biomaterials combined with recombinant proteins to transform into custom-made prefabricated bone grafts for human reconstruction. The osteogenic proteins of the TGF-beta superfamily, BMPs/OPs and TGF-betas, the last endowed with the striking prerogative of inducing endochondral bone formation in primates only, are helping to engineer skeletal reconstruction in molecular terms. (+info)
Detection of natural infection with Mycobacterium intracellulare in healthy wild-caught Chacma baboons (Papio ursinus) by ESAT-6 and CFP-10 IFN-gamma ELISPOT tests following a tuberculosis outbreak.
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