Cutaneous melanoma with metastasis in a cynomolgus monkey (Macaca fascicularis).

BACKGROUND: A 3.3-year-old-male cynomolgus macaque (Macaca fascicularis) showed a focally extensive soft, dark, discoid dermal mass, 0.5 cm in diameter, on the dorsal surface of the right hind foot, over the fourth and fifth metatarsal bones. METHODS AND RESULTS Microscopic examination revealed a cutaneous melanoma with local lymphatic invasion, characterized by neoplastic melanocytes within the subcapsular sinus of popliteal and inguinal lymph nodes. The diagnosis was confirmed by immunohistochemistry and transmission electron microscopy. CONCLUSIONS: To our knowledge, this is the first documented case of melanoma in a cynomolgus monkey.

Persistency of adenoviral-mediated lysostaphin expression in goat mammary glands.

Gene therapy has great potential to enable synthesis of protein molecules in targeted cells of an animal. One application may be the production of antibacterial enzymes by the mammary gland as a means of preventing or treating mastitis. We have previously demonstrated that goat mammary cells are capable of producing lysostaphin, an antistaphylococcal enzyme, after being transduced in vivo with a recombinant adenoviral vector containing a modified lysostaphin gene (Ad-lys). The current study examined duration of expression, and antibody response to lysostaphin and the adenoviral vector. Following intramammary infusion into nonlactating goats (n = 4), recovery of transducible adenoviral vector in mammary secretions persisted for 11 d. Transducible vector was not detected in serum, saliva, urine, or feces. Peak lysostaphin concentrations (< 20 microg/mL) in mammary secretions of infused udders were detected approximately 1 wk postinfusion, and generally returned to undetectable levels after an additional 1 to 2 wk. The poor persistency of expression was likely due to the very potent immune response to both the adenovirus and the expressed lysostaphin. Serum IgG antibodies recognizing the adenoviral vector developed within 7 d of the infusion, and titers rose dramatically to greater than 1:1 x 10(5). Similar titers of serum IgG antibodies to lysostaphin developed in 3 goats, with more moderate titers in the fourth goat. The antibody response to lysostaphin was delayed by approximately 4 d in comparison to the response to the adenovirus. Serum IgG antibody profiles were reflected in mammary secretions. No IgA antibodies to adenovirus or lysostaphin were detected in sera or mammary secretion. We demonstrate that while the lysostaphin gene can be introduced to the mammary gland using an adenoviral-mediated gene transfer technique, the strong immune response that it provokes makes the approach unsuitable for combating mastitis.

Characteristics of carbon dioxide-induced antinociception.

This lab previously showed that brief inhalation of high concentrations of CO2 results in a prolonged, moderate antinociception with characteristics of a nonopiate, hormonal mechanism. To further characterize and optimize this response, the effect of a variety of methodological, biological, and stress-related manipulations were studied. No significant differences were found in the CO2-induced response between animals that were tested during different portions of their diurnal cycles, in rats that were unhandled or habituated to nociceptive testing conditions, in male vs. female rats, or in animals of differing weights. Additionally, restraining animals prior to CO2 exposure induced a hot plate antinociceptive response that was not different from the response produced by CO2 alone. In contrast, on the tail flick test, a CO2 -restraint interaction both increased and decreased the response at different times. The present findings show that CO2 antinociception: a) is a reliable phenomenon not altered by a variety of methodological and biological conditions, and b) has characteristics of a novel, stress-mediated antinociceptive response.

Prolonged antinociception following carbon dioxide anesthesia in the laboratory rat.

In the laboratory rat, inhalation (30 s) of high (> 70%) CO2 concentrations resulted in short-term (1-3 min) anesthesia, followed by a prolonged (up to 60 min) mild antinociception. Exposure to 100% CO2 resulted in significant thermal (hot-plate, 52 degrees, and tail-flick) and mechanical (tail-pinch, 886 g force) antinociception. Control animals, placed in the same chamber filled with air, showed no such effects. Rats exposed to 70% CO2 exhibited effects on the hot plate comparable to those seen after inhalation of 100% CO2, indicating that the response is not due to CO2-induced hypoxia. Additionally, recovery from halothane-induced anesthesia of comparable duration did not result in antinociception, confirming that anesthesia alone is not sufficient to produce the effect. Pretreatment with the opiate antagonist naltrexone (0.1-10 mg/kg i.p.) did not diminish the CO2-induced antinociception, suggesting that endogenous opioids are not obligatory in the mechanism of this response. Furthermore, hypophysectomy abolished hot-plate antinociception in animals exposed to 100% CO2 while sham-treated controls exhibited a pattern of hot-plate responses similar to that reported above. Taken together, these findings show that: (1) recovery from CO2-induced anesthesia results in a prolonged mild antinociception, detectable with thermal and mechanical nociceptive tests; and (2) this response may represent a novel from of environmentally induced antinociception, mediated by a non-opiate hormonal substance.