Tick paralysis in a free-ranging bobcat (Lynx rufus).

CASE DESCRIPTION: A free-ranging male bobcat (Lynx rufus) was evaluated because of signs of pelvic limb paralysis. CLINICAL FINDINGS: Physical examination of the anesthetized animal revealed tick infestation, normal mentation, and a lack of evidence of traumatic injuries. Radiography revealed no clinically relevant abnormalities. Hematologic analysis results were generally unremarkable, and serologic tests for exposure to feline coronavirus, FeLV, FIV, and Toxoplasma gondii were negative. Results of PCR assays for flea- and common tick-borne organisms other than Bartonella clarridgeiae were negative. TREATMENT AND OUTCOME: Ticks were manually removed, and the patient received supportive care and fipronil treatment. The bobcat made a full recovery within 72 hours after treatment for ticks, and a presumptive diagnosis of tick paralysis was made. Identified tick species included Dermacenter variabilis, Amblyomma americanum, and Ixodes scapularis. CLINICAL RELEVANCE: To the authors' knowledge, tick paralysis has not previously been reported in felids outside Australia. This disease should be considered a differential diagnosis in felids, including exotic cats, with signs of neuromuscular disease of unknown etiopathogenesis.

ANTEMORTEM DIAGNOSIS AND SUCCESSFUL TREATMENT OF A COMPLETE MOLAR PREGNANCY IN A GERIATRIC BONOBO ( PAN PANISCUS).

A 47-yr-old multiparous female bonobo ( Pan paniscus) tested positive for pregnancy on a routine urine test. Because this geriatric animal was considered postreproductive, oral contraception had been discontinued. Sequential transabdominal ultrasound evaluations were performed under voluntary behavior and revealed that the uterus contained a mass of heterogenous tissue which was rapidly increasing in size. Due to a lack of normal fetal development and the ultrasonographic appearance of the uterine tissue, a molar pregnancy was suspected. Ovariohysterectomy was performed, and a complete hydatidiform mole was confirmed through human chorionic gonadotropin levels as well as gross and histological examination of the uterus. To the authors' knowledge, this is the first time a complete molar pregnancy has been reported antemortem in a nonhuman great ape, although a single case of partial hydatidiform mole was previously documented in a chimpanzee on postmortem examination. This case describes the successful medical and surgical management of complete molar pregnancy in a bonobo and provides support for extending the age range of birth control recommendations in geriatric captive great apes that exhibit active breeding behavior.

Hematologic, plasma biochemistry, and select nutrient values in captive smooth dogfish (Mustelus canis).

The Indianapolis Zoo maintains a large collection of smooth dogfish (Mustelus canis). During the first several years of captivity, there was a period of high mortality in adult, wild-caught sharks in the collection. Smooth dogfish with superficial abrasions would rapidly succumb to infection and death, regardless of the treatment approach. Although the sharks did successfully produce viable offspring, there was an elevated pup mortality rate, with 0% of the pups reaching 1 yr of age during the same period of high mortality in adult sharks. This poor response to captivity prompted interest in the physiologic response of these animals to illness. The objective of this investigation was to establish a preliminary data set of hematologic and plasma chemistry reference intervals, along with select nutrient parameters specific to wild-caught adults maintained in prolonged captivity (i.e., greater than 22 mo). Blood samples were collected from 20 clinically healthy, male (n = 10) and female (n = 10) dogfish sharks at the Oceans facility at the Indianapolis Zoo. Although gender differences in mortality rate were not apparent, complete blood cell counts, plasma biochemical profiles, and select nutrient analyses were performed and analyzed accordingly. Statistically significant differences (P < or = 0.05) specific to sex were determined for parameters including packed cell volume (PCV), absolute and relative fine eosinophilic granulocytes, relative percentage of coarse eosinophilic granulocytes, globulins, the albumin/globulin ratio, total protein, phosphorus, iron, selenium and copper. White blood cell counts appear to be lower in this species compared to other captive elasmobranchs. Further research into appropriate hematology standards including nutritional parameters appears warranted.

Pre-assembly of STAT4 with the human IFN-alpha/beta receptor-2 subunit is mediated by the STAT4 N-domain.

CD4(+) T cells regulate adaptive responses to pathogens by secreting unique subsets of cytokines that mediate inflammatory processes. The innate cytokines IL-12 and IFN-alpha/beta regulate type I responses and promote acute IFN-gamma secretion through the activation of the STAT4 transcription factor. Although IL-12-induced STAT4 activation is a conserved pathway across species, IFN-alpha/beta-dependent STAT4 phosphorylation does not occur as efficiently in mice as it does in human T cells. In order to understand this species-specific pathway for IFN-alpha/beta-dependent STAT4 activation, we have examined the molecular basis of STAT4 recruitment by the human IFNAR. In this report, we demonstrate that the N-domain of STAT4 interacts with the cytoplasmic domain of the human, but not the murine IFNAR2 subunit. This interaction mapped to a membrane-proximal segment of the hIFNAR2 spanning amino acids 299-333. Deletion of this region within the hIFNAR2 completely abolishes IFN-alpha/beta-dependent STAT4 tyrosine phosphorylation when expressed in human IFNAR2-deficient fibroblasts. Thus, the human IFNAR2 cytoplasmic domain serves to link STAT4 to the IFNAR as a pre-assembled complex that facilitates cytokine-driven STAT4 activation.

IL-12, but not IFN-alpha, promotes STAT4 activation and Th1 development in murine CD4+ T cells expressing a chimeric murine/human Stat2 gene.

Humans and mice have evolved distinct pathways for Th1 cell development. Although IL-12 promotes CD4(+) Th1 development in both murine and human T cells, IFN-alphabeta drives Th1 development only in human cells. This IFN-alphabeta-dependent pathway is not conserved in the mouse species due in part to a specific mutation within murine Stat2. Restoration of this pathway in murine T cells would provide the opportunity to more closely model specific human disease states that rely on CD4(+) T cell responses to IFN-alphabeta. To this end, the C terminus of murine Stat2, harboring the mutation, was replaced with the corresponding human Stat2 sequence by a knockin targeting strategy within murine embryonic stem cells. Chimeric m/h Stat2 knockin mice were healthy, bred normally, and exhibited a normal lymphoid compartment. Furthermore, the murine/human STAT2 protein was expressed in murine CD4(+) T cells and was activated by murine IFN-alpha signaling. However, the murine/human STAT2 protein was insufficient to restore full IFN-alpha-driven Th1 development as defined by IFN-gamma expression. Furthermore, IL-12, but not IFN-alpha, promoted acute IFN-gamma secretion in collaboration with IL-18 stimulation in both CD4(+) and CD8(+) T cells. The inability of T cells to commit to Th1 development correlated with the lack of STAT4 phosphorylation in response to IFN-alpha. This finding suggests that, although the C terminus of human STAT2 is required for STAT4 recruitment and activation by the human type I IFNAR (IFN-alphabetaR), it is not sufficient to restore this process through the murine IFNAR complex.