Th1 genetic adjuvants modulate immune responses in neonates.

In these studies, we address the ability of DNA encoding Th1 cytokines to bias the isotype of antibody raised by neonatal or adult immunization with an influenza hemagglutinin expressing DNA (HA-DNA). Neonatal mice coimmunized with HA-DNA and either IL-12 or IFN-gamma-expressing DNA developed IgG2a-biased immune responses, regardless of inoculation method. In contrast, the Th1 genetic adjuvants had no effect on IgG subtype patterns in adults.

Cocaine-induced changes in extracellular dopamine determined by microdialysis in awake squirrel monkeys.

Rationale: The behavioral effects of cocaine have been linked to brain dopamine systems. Extending the findings to neurochemical studies in the squirrel monkey would enhance our understanding of the behavioral pharmacology of cocaine in nonhuman primates.

Objectives: The present studies characterized the effects of cocaine and the selective dopamine uptake inhibitor GBR 12909 on extracellular dopamine in the caudate nucleus of awake squirrel monkeys through microdialysis experiments.

Rapid CD4(+) T-cell loss induced by human immunodeficiency virus type 1(NC) in uninfected and previously infected chimpanzees.

To investigate the pathogenicity of a virus originating in a chimpanzee with AIDS (C499), two chimpanzees were inoculated with a plasma-derived isolate termed human immunodeficiency virus type 1(NC) (HIV-1(NC)). A previously uninfected chimpanzee, C534, experienced rapid peripheral CD4(+) T-cell loss to fewer than 26 cells/microl by 14 weeks after infection. CD4(+) T-cell depletion was associated with high plasma HIV-1 loads but a low virus burden in the peripheral lymph node.

Behavioral evaluation of hemiparkinsonian MPTP monkeys following dopamine pharmacological manipulation and adrenal co-graft transplantation.

Bradykinesia and rigidity are the symptoms that most directly correlate with loss of striatal dopamine in Parkinson's disease. In the hemiparkinsonian (HP) monkey, this is represented by paucity of movement as measured by coli puterized movement analysis, diminished manual dexterity on clinical examination, and diminished performance on operant behavioral tasks. The present study used an MPTP-induced HP model in rhesus monkeys to evaluate the effectiveness of adrenal medullary and peripheral nerve co-grafts in diminishing parkinsonian symptoms.

Behavioral effects of AMI-193, a 5-HT(2A)- and dopamine D(2)-receptor antagonist, in the squirrel monkey.

8-[3-(4-Fluorophenoxy) propyl]-1-phenyl-1,3,8-triazaspiro[4, 5]decan-4-one (AMI-193) was developed as a 5-HT(2A)-selective antagonist with in vivo activity suitable for behavioral studies. However, AMI-193 is a potent dopamine D(2)-receptor antagonist with low nanomolar affinity. Accordingly, D(2)-actions may contribute to its behavioral pharmacology.

Recent advances in the biology of addiction.

Recent research into the biologic basis of drug addiction continues to offer considerable promise for understanding how neurochemistry, pharmacology, and molecular biology relate to the reinforcing effects of abused drugs. One area of research is the development and pharmacologic and neurochemical characterization of cocaine and opiate polydrug abuse, a growing subset of the drug abuse population. Considerable advances have also been made in understanding how chronic and persistent drug use induces biochemical and molecular biologic adaptations in brain regions related to drug reinforcement.

Anatomy of the dopamine system in the basal ganglia.

The dopaminergic nigropallidal and nigrosubthalamic projections control the activity of the globus pallidus and subthalamic nucleus neurons in both normal and pathological conditions. Intrastriatal dopaminergic neurons increase substantially in animal models of Parkinson's disease. They contain GABA, display the ultrastructural features of interneurons and form axo-axonic synapses with putative cortical-like glutamatergic boutons.

Activation of metabotropic glutamate receptor 5 has direct excitatory effects and potentiates NMDA receptor currents in neurons of the subthalamic nucleus.

The subthalamic nucleus (STN) is a key nucleus in the basal ganglia motor circuit that provides the major glutamatergic excitatory input to the basal ganglia output nuclei. The STN plays an important role in normal motor function, as well as in pathological conditions such as Parkinson's disease (PD) and related disorders. Development of a complete understanding of the roles of the STN in motor control and the pathophysiological changes in STN that underlie PD will require a detailed understanding of the mechanisms involved in regulation of excitability of STN neurons.

Capuchins do cooperate: the advantage of an intuitive task.

We used a cooperative pulling task to examine proximate aspects of cooperation in captive brown capuchin monkeys, Cebus apella. Specifically, our goal was to determine whether capuchins can learn the contingency between their partner's participation in a task and its successful completion. We examined whether the monkeys visually monitored their partners and adjusted pulling behaviour according to their partner's presence.

Guided bone regeneration of large mandibular defects in a primate model.

Background: An earlier publication from our laboratory described the use of guided bone regeneration to fill large bone voids in the mandible created through en bloc resection in primates. The present report is an embellishment of this paper and describes bone regeneration experiments in 18 adult male Macaca mulatta monkeys to determine how long membranes must be in position to promote guided bone regeneration.

Methods: Thirty-six lesions were created in the mandibles of 18 monkeys in a standardized mandibular defect of 8 x 19 mm.

Effects of Mpl ligands on platelet production and function in nonhuman primates.

Endogenous thrombopoietin (TPO) stimulates platelet production in nonhuman primates dose-dependentbyinducing megakaryocyte development from early marrow hematopoietic progenitors and subsequent proliferation and endoreduplication. Recombinant human TPO, nonpegylated or pegylated recombinant human megakaryocyte growth and development factor produce log-linear responses in peak peripheral platelet counts (or peripheral platelet mass turnover), platelet TPO receptor density, and marrow megakaryocyte volume, ploidy, number and mass. Mpl ligand therapy sustains normal peripheral platelet concentrations following myelosuppressive chemotherapy in baboons and corrects peripheral platelet counts in HIV-infected chimpanzees with severe thrombocytopenia.

Progressive infection in a subset of HIV-1-positive chimpanzees.

Chimpanzees are susceptible to infection with human immunodeficiency virus (HIV)-1; however, infected animals usually maintain normal numbers of CD4(+) T lymphocytes and do not develop immunodeficiency. We have examined 10 chronically infected HIV-1-positive chimpanzees for evidence of progressive infection. In addition to 1 animal that developed AIDS, 3 chimpanzees exhibit evidence of progressive HIV infection.

Attitudinal reciprocity in food sharing among brown capuchin monkeys.

Capuchin monkeys (Cebus apella) share food even if separated by a mesh restraint. Pairs of capuchins were moved into a test chamber in which one of them received apple pieces for 20 min, and the other received carrot pieces for the next 20 min. Previous research had shown a correlation between the rate of food transfer in both directions across female-female dyads.

Use of intrauterine devices (IUDs) for contraception in the common chimpanzee (Pan troglodytes).

The common chimpanzee (Pan troglodytes) is a species phylogenetically very close to man. It was not many years ago that the captive population of chimpanzees (P. troglodytes) was considered at risk because of perceived problems with reproductive success.

GABA(B) and group I metabotropic glutamate receptors in the striatopallidal complex in primates.

Glutamate and GABA neurotransmission is mediated through various types of ionotropic and metabotropic receptors. In this review, we summarise some of our recent findings on the subcellular and subsynaptic localisation of GABA(B) and group I metabotropic glutamate receptors in the striatopallidal complex of monkeys. Polyclonal antibodies that specifically recognise GABA(B)R1, mGluR1a and mGluR5 receptor subtypes were used for immunoperoxidase and pre-embedding immunogold techniques at the light and electron microscope levels.

Primates--a natural heritage of conflict resolution.

The traditional notion of aggression as an antisocial instinct is being replaced by a framework that considers it a tool of competition and negotiation. When survival depends on mutual assistance, the expression of aggression is constrained by the need to maintain beneficial relationships. Moreover, evolution has produced ways of countering its disruptive consequences.

Activity of the hypothalamic-pituitary-adrenal axis is altered by aging and exposure to social stress in female rhesus monkeys.

Age-related changes in glucocorticoid negative feedback inhibition of hypothalamic CRF and pituitary ACTH are observed in rodents. Attempts to study similar effects in humans have produced mixed results due in part to the difficulty in matching older subjects on social and lifestyle variables. The present study used female rhesus monkeys as a model for women by comparing young adult (n = 20) to old (n = 20) females to test the hypotheses that the hypothalamic-pituitary-adrenal axis is altered in older animals and that this difference is exacerbated by exposure to social stress.

Injury risks among chimpanzees in three housing conditions.

Meeting the psychological needs of chimpanzees (Pan troglodytes) can be a challenge given their aggressiveness on the one hand and the complexity of their social lives on the other. It is unclear how to balance the need to provide opportunities for species-appropriate behavior against potential risks of injury chimpanzees may inflict on each other. This study evaluates the suggestion that simpler social environments protect chimpanzees from wounding.

Intra-ventral tegmental area injection of rat cocaine and amphetamine-regulated transcript peptide 55-102 induces locomotor activity and promotes conditioned place preference.

Cocaine- and amphetamine-regulated transcript (CART) is a novel mRNA that has been reported to be increased by acute psychostimulant administration, and that may be involved in the effects of psychostimulants. In this study, we examined the effect of centrally administered CART peptides on locomotor activity and conditioned place preference in the rat. CART peptide fragments were bilaterally injected into the ventral tegmental area.

Social amnesia in mice lacking the oxytocin gene.

The development of social familiarity in rodents depends predominantly on olfactory cues and can critically influence reproductive success. Researchers have operationally defined this memory by a reliable decrease in olfactory investigation in repeated or prolonged encounters with a conspecific. Brain oxytocin (OT) and vasopressin (AVP) seem to modulate a range of social behaviour from parental care to mate guarding.

Cognitive function in aged ovariectomized female rhesus monkeys.

To determine whether ovariectomy exacerbates age-related cognitive decline, the performance of 6 aged monkeys that had been ovariectomized early in life (OVX-Aged) was compared to that of 8 age-matched controls with intact ovaries (INT-Aged) and that of 5 young controls with intact ovaries (INT-Young) in tasks of visual recognition memory, object and spatial memory, and executive function. The OVX-Aged monkeys were marginally more impaired than the INT-Aged monkeys on the delayed nonmatching-to-sample with a 600-s delay. In contrast, they performed significantly better than the INT-Aged controls on the spatial condition of the delayed recognition span test.

Presynaptic NMDA receptor subunit immunoreactivity in GABAergic terminals in rat brain.

N-methyl-D-aspartate (NMDA) receptors are commonly found post-synaptically; they mediate fast excitatory neurotransmission in the central nervous system. In this study, we provide immunocytochemical data supporting the existence of presynaptic NMDA receptors in GABAergic terminals using polyclonal antisera raised against the C-terminus of the NMDAR1 subunit. At the light microscope level, rich plexuses of NMDAR1-positive varicose fibers were found in various nuclei in the basal forebrain (bed nucleus of stria terminalis, septum, parastrial nucleus, vascular organ of the lamina terminalis), thalamus (paraventricular nucleus, midline nuclei), and hypothalamus (parvocellular paraventricular nucleus, arcuate nucleus, preoptic nucleus, suprachiasmatic nucleus).

Immunocytochemical characterization of the mitochondrially encoded ND1 subunit of complex I (NADH : ubiquinone oxidoreductase) in rat brain.

In Parkinson's disease, there is a selective defect in complex I of the electron transfer chain. To better understand complex I and its involvement in neurodegenerative disease, we raised an antibody against a conserved epitope of the human mitochondrially encoded subunit 1 of complex I (ND1). Antibodies were affinity purified and assessed by ELISA, immunoblotting, and immunocytochemistry.