Self-Injurious behavior in rhesus macaques: Issues and challenges.

Some monkeys housed in research facilities develop abnormal behavior ranging from stereotypic to the more serious condition of self-injurious behavior (SIB). We initially sought to understand how and why monkeys engaged in SIB and more importantly why only a small percentage of laboratory monkeys, with seemingly similar housing and background, developed this disorder. Of particular importance was the recognition that different pathways might lead to SIB and that strong individual differences would affect the manifestation of this disorder and the response to treatment.

Use of OpdA, an organophosphorus (OP) hydrolase, prevents lethality in an African green monkey model of acute OP poisoning.

Organophosphorus (OP) pesticides are a diverse class of acetylcholinesterase (AChE) inhibitors that are responsible for tremendous morbidity and mortality worldwide, killing approximately 300,000 people annually. Enzymatic hydrolysis of OPs is a potential therapy for acute poisoning. OpdA, an OP hydrolase isolated from Agrobacterium radiobacter, has been shown to decrease lethality in rodent models of OP poisoning.

Multiple endocardial neurofibromas in a rosy-billed pochard (Netta peposaca).

Endocardial neoplasms are uncommon in veterinary species with most cases restricted to endocardial schwannomas in aged rats. A 15-year-old male rosy-billed pochard (Netta peposaca) was diagnosed following necropsy with numerous, proliferative endocardial masses. Histologically, these masses were composed of interlacing streams and bundles of neoplastic spindle cells supported by a fine fibrovascular stroma.

Small intestinal adenocarcinoma in common marmosets (Callithrix jacchus).

Small intestinal adenocarcinomas are uncommon neoplasms that are rarely reported in nonhuman primates. These neoplasms are also rare in humans, although they are thought to share a similar pathogenesis with the more common colorectal carcinoma. Herein the authors report the clinical, histologic, immunohistochemical, and molecular characteristics of small intestinal adenocarcinoma in 10 common marmosets (Callithrix jacchus).

Histologic and immunohistochemical characterization of pheochromocytoma in 6 cotton-top tamarins (Saguinus oedipus).

Pheochromocytomas are uncommon neoplasms of the adrenal medulla that are most frequently reported in rats and select mouse strains. In many cases, especially those in man, pheochromocytoma is associated with familial tumor syndromes, because of inherited mutations in a variety of proto-oncogenes and tumor suppressor genes. Nonhuman primates are valuable animal models for a variety of human diseases because of their similar anatomy and physiology; however, cases of pheochromocytomas have only rarely been reported in nonhuman primates.

Viral and host correlates of serum resistin in simian AIDS.

Resistin is an adipocytokine with a proposed dual role in metabolism and inflammation. In light of the ability to promote inflammatory responses, adipocytokines may prove key factors in modulating the host response to HIV. This study utilizes the simian immunodeficiency virus (SIV) model of HIV/AIDS to investigate changes in serum resistin levels following dietary intervention and SIV infection and determine associations with measures of body composition and disease severity.

Downregulation of gamma interferon receptor 1 by Kaposi's sarcoma-associated herpesvirus K3 and K5.

Upon viral infection, the major defense mounted by the host immune system is activation of the interferon (IFN)-mediated antiviral pathway. In order to complete their life cycles, viruses must modulate the host IFN-mediated immune response. The K3 and K5 proteins of a human tumor-inducing herpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV), have been shown to downregulate the surface expression of host immune modulatory receptors by increasing their endocytosis rates, which leads to suppression of cell-mediated immunity.

Receptor regulation of gene expression of axon guidance molecules: implications for adaptation.

Axon guidance molecules, critical for neurodevelopment, are also implicated in morphological and other neurodaptative changes mediated by physiological or pharmacological events in adult brain. As an example, the psychostimulant cocaine markedly alters axon guidance molecules in adult brain of cocaine-treated rats. To decipher a potential link between drug-induced activation of G-protein-coupled receptors (GPCRs) and modulation of axon guidance molecules, we investigated whether GPCR activity in a SK-N-MC human neuroepithelioma cell line (which expresses low levels of D1 dopamine receptors) affects gene expression of axon guidance molecules (semaphorins, ephrins, netrins, and their receptors).

Systemic arteriopathy in SIV-infected rhesus macaques (Macaca mulatta).

Background: Severe disseminated vasculopathy was observed in two simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta). These animals developed clinical signs of AIDS, including lymphadenopathy, weight loss, diarrhea and collapse.

Results And Discussion: Grossly, both animals showed emaciation, lymphadenopathy, vegetations on the mitral valve, renal infarcts and a dilated intestine; one animal had multifocal hemorrhages in multiple organs.

PRA1 co-localizes with envelope but does not influence primate lentivirus production, infectivity or envelope incorporation.

The results of yeast and mammalian two-hybrid assays previously indicated complex formation between prenylated Rab acceptor 1 (PRA1) and the cytoplasmic domain of gp41 (gp41CD) for both the human and simian immunodeficiency viruses [Evans, D. T., Tilman, K.

Inhibition of interferon-mediated antiviral activity by murine gammaherpesvirus 68 latency-associated M2 protein.

Upon viral infection, the major defense mounted by the host immune system is the activation of the interferon (IFN)-mediated antiviral pathway. In order to complete their life cycle, viruses that are obligatory intracellular parasites must modulate the host IFN-mediated immune response. Murine gammaherpesvirus 68 (gammaHV68) infects a wide range of cell types and establishes latent infections in mice.

GB virus B infection of the common marmoset (Callithrix jacchus) and associated liver pathology.

GB virus B (GBV-B) is a flavivirus that is related closely to hepatitis C virus (HCV) and induces an acute hepatitis when inoculated into several species of New World primates. Common marmosets (Callithrix jacchus) are a widely available, non-endangered primate species that is susceptible to GBV-B infection and develops a characteristic acute hepatitis. Here, animals were found to be susceptible to serially passaged serum and GBV-B transcripts.

Modulation of T-cell receptor signal transduction by herpesvirus signaling adaptor protein.

Because of its central regulatory role, T-cell receptor (TCR) signal transduction is a common target of viruses. We report here the identification of a small signaling protein, ORF5, of the T-lymphotropic tumor virus herpesvirus saimiri (HVS). ORF5 is predicted to contain 89 to 91 amino acids with an amino-terminal myristoylation site and six SH2 binding motifs, showing structural similarity to cellular LAT (linker for activation of T cells).

Altered hypothalamic-pituitary-adrenocortical function in rhesus monkeys (Macaca mulatta) with self-injurious behavior.

Individually housed rhesus monkeys sometimes spontaneously develop self-injurious behavior (SIB) in the form of self-directed biting that, on occasion, results in severe tissue damage and mutilation. We previously demonstrated lower levels of plasma cortisol in rhesus monkeys with a history of self-wounding (SW) when compared to non-wounders (NW). Furthermore, cortisol levels were negatively correlated with rates of self-directed biting.

Assorted mutations in the envelope gene of simian immunodeficiency virus lead to loss of neutralization resistance against antibodies representing a broad spectrum of specificities.

Simian immunodeficiency virus (SIV) of macaques isolate SIVmac239 is highly resistant to neutralization by polyclonal antisera or monoclonal antibodies, a property that it shares with most primary isolates of human immunodeficiency virus type 1 (HIV-1). This resistance is important for the ability of the virus to persist at high levels in vivo. To explore the physical features of the viral envelope complex that contribute to the neutralization-resistant phenotype, we examined a panel of SIVmac239 derivatives for sensitivity to neutralization by a large collection of monoclonal antibodies (MAbs).

Structural analysis of the Kaposi's sarcoma-associated herpesvirus K1 protein.

The K1 protein of Kaposi's sarcoma-associated herpesvirus (KSHV) efficiently transduces extracellular signals to elicit cellular activation events through its cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM). In addition, the extracellular domain of K1 demonstrates regional homology with the immunoglobulin (Ig) family and contains conserved regions (C1 and C2) and variable regions (V1 and V2). To generate mouse monoclonal antibodies directed against the KSHV K1 protein, BALB/c mice were primed and given boosters with K1 protein purified from mammalian cells.

Stereotypic and self-injurious behavior in rhesus macaques: a survey and retrospective analysis of environment and early experience.

Abnormal behavior in captive rhesus monkeys can range from active whole-body and self-directed stereotypies to self-injurious behavior (SIB). Although abnormal behaviors are common in singly-housed rhesus monkeys, the type and frequency of these behaviors are highly variable across individual animals, and the factors influencing them are equally varied. The purpose of this investigation was to survey abnormal behavior in a large population of rhesus macaques, to characterize the relationship between stereotypies and self-injury, and to identify potential risk factors for these aberrant behaviors.

Role of the hypothalamic-pituitary-adrenal axis in reinstatement of cocaine-seeking behavior in squirrel monkeys.

Rationale: Stress has been suggested to play a role in relapse to cocaine-seeking behavior. An important physiological system activated by stress is the hypothalamic-pituitary-adrenal (HPA) axis; however, evidence for a role of HPA axis activation in cocaine relapse has been contradictory.

Objectives: This study examined the effects of pharmacological stimulation of the HPA axis on reinstatement of drug-seeking behavior and salivary cortisol levels in a non-human primate model of cocaine relapse.

Global changes in Kaposi's sarcoma-associated virus gene expression patterns following expression of a tetracycline-inducible Rta transactivator.

An important step in the herpesvirus life cycle is the switch from latency to lytic reactivation. In order to study the life cycle of Kaposi's sarcoma-associated herpesvirus (KSHV), we developed a gene expression system in KSHV-infected primary effusion lymphoma cells. This system uses Flp-mediated efficient recombination and tetracycline-inducible expression.

Principal role of TRAP/mediator and SWI/SNF complexes in Kaposi's sarcoma-associated herpesvirus RTA-mediated lytic reactivation.

An important step in the herpesvirus life cycle is the switch from latency to lytic reactivation. The RTA transcription activator of Kaposi's sarcoma-associated herpesvirus (KSHV) acts as a molecular switch for lytic reactivation. Here we demonstrate that KSHV RTA recruits CBP, the SWI/SNF chromatin remodeling complex, and the TRAP/Mediator coactivator into viral promoters through interactions with a short acidic sequence in the carboxyl region and that this recruitment is essential for RTA-dependent viral gene expression.

Attenuation of relapse to cocaine seeking by dopamine D1 receptor agonists and antagonists in non-human primates.

Rationale: Dopamine D(1) receptor agonists and antagonists attenuate reinstatement of cocaine seeking in a non-human primate model of relapse. The mechanisms by which these different classes of D(1) receptor drugs produce these similar effects on cocaine seeking are unknown.

Objectives: This study investigated how D(1) receptor agonists and antagonists alter the shape and position of the dose-response function for reinstatement of drug seeking induced by a cocaine prime accompanied by restoration of the cocaine-paired stimulus.

Suppression of cocaine- and food-maintained behavior by the D2-like receptor partial agonist terguride in squirrel monkeys.

Rationale: The D2-like receptor partial agonist terguride has a profile of behavioral effects in rats that suggests potential benefit as a pharmacotherapy for cocaine addiction.

Objectives: The present study investigated the effects of terguride on cocaine- and food-maintained behavior in squirrel monkeys.

Methods: Squirrel monkeys were trained to respond on a second-order schedule (FI 10 min, FR 10 or 30:S) of either i.

Mucosal priming of simian immunodeficiency virus-specific cytotoxic T-lymphocyte responses in rhesus macaques by the Salmonella type III secretion antigen delivery system.

Nearly all human immunodeficiency virus (HIV) infections are acquired mucosally, and the gut-associated lymphoid tissues are important sites for early virus replication. Thus, vaccine strategies designed to prime virus-specific cytotoxic T lymphocyte (CTL) responses that home to mucosal compartments may be particularly effective at preventing or containing HIV infection. The Salmonella type III secretion system has been shown to be an effective approach for stimulating mucosal CTL responses in mice.

Self-injurious behavior in male rhesus macaques does not reflect externally directed aggression.

Self-injurious behaviors (SIB), such as self-biting and self-wounding, have been observed in a small percentage of captive nonhuman primates. Because rhesus monkeys that exhibit SIB also tend to be more aggressive, it was hypothesized that SIB is related to externally directed aggression and is associated with contexts in which physical contact between participants is prevented. The purpose of this study was to test the hypothesized relationship between SIB and outward aggression.