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.

Mechanistic toxicogenomic analysis of WAY-144122 administration in Sprague-Dawley rats.

Application of global gene expression analysis in the study of mechanisms of toxicity could provide a more comprehensive interpretation of the molecular basis of drug action. WAY-144122 has pharmacological activity against several targets improving insulin responsiveness and favorably altering lipid profiles. Normal rats treated with suprapharmacological doses of WAY-144122 for 28 days exhibited drug-related effects in the liver and ovary. To determine the molecular mechanism underlying these effects, we employed global gene expression profiling to measure RNA levels in these target organs obtained from WAY-144122-treated rats administered test article for 1, 3, 7, and 14 days. Genes altered in expression by WAY-144122 were functionally categorized and related to their biological activity. In the liver, WAY-144122 caused a widespread up-regulation of genes involved in lipid mobilization, peroxisomal proliferation, and fatty acid beta-oxidation. In the ovary, we observed reduced expression of genes encoding luteinizing hormone receptor, follistatin, and enzymes in the estradiol synthesis pathway. Transcriptional changes in both organs precede histopathological effects. Profiling analysis allowed us to formulate hypotheses for molecular mechanisms underlying the physiological observations. In the liver, transcriptional changes suggest that WAY-144122 induced increased metabolic activity and peroxisomal proliferation resulting in increased liver weight and hepatocellular hypertrophy. We propose decreased estradiol synthesis as the underlying mechanism for the observed follicular atrophy in the ovary. Importantly, in this study, we have identified potential molecular mechanisms of drug effect in expression profiles before observation of physiological changes.

Acute pulmonary lesions in sheep experimentally infected with bovine viral diarrhoea virus.

Six sheep, aged 6-8 months and seronegative for pestivirus, were inoculated intranasally, through the tracheal wall, and intrabronchially with a non-cytopathogenic isolate of bovine viral diarrhoea virus (ncpBVDV). Infected sheep were killed in pairs on post-inoculation day (PID) 2, 4 and 6. They all exhibited transient leucopenia or lymphopenia, or both. Platelet counts decreased but remained within normal limits. BVDV was isolated from buffy coats and tissues of all sheep inoculated with ncpBVDV but not from two uninfected control animals. Pulmonary lesions, evident in ncpBVDV-inoculated sheep, consisted of moderate oedema with multifocal alveolar septal necrosis and haemorrhage, infiltrates of mononuclear inflammatory cells, and degenerative changes in alveolar epithelium, endothelium and pulmonary intravascular macrophages. Additionally, there was morphological evidence of platelet activation and pulmonary intravascular macrophage stimulation. Lesions were not observed in the two control sheep.

Pathogenesis of infection induced by an adenovirus isolated from a goat.

OBJECTIVE: To determine the pathogenic potential of an adenovirus isolated from a goat. ANIMALS: 14 colostrum-deprived, isolation-reared goat kids approximately 3 weeks old. PROCEDURE: Kids were inoculated with either cell culture fluid containing adenovirus (n = 10) or uninfected cell culture fluid (n = 4): 2 ml transtracheally and 1 ml/nostril. Clinical signs of disease and rectal temperature were recorded daily; nasal secretion and fecal specimens were collected daily. Control kids were necropsied, 2/d, on postinoculation days (PID) 5 and 10. Virus-inoculated kids were necropsied on PID 3, 5, 7, 10, and 28. After necropsy, lung, liver, kidney, and brain specimens were aseptically collected for virus isolation attempts. Tracheal fluid was collected on sterile cotton swabs. Turbinate, trachea, lung, mediastinal lymph node, liver, kidney, duodenum, jejunum, ileum, mesenteric lymph node, colon, and brain specimens were collected for histologic evaluation. RESULTS: Kids developed mild-to-moderate clinical respiratory tract infection. Virus was recovered consistently from nasal secretion and sporadically from fecal specimens. Grossly, there were multiple areas of atelectasis and hyperemia, principally in the cranioventral portion of the lungs. Microscopically, there was detachment and sloughing of foci of epithelial cells of the terminal bronchioles and alveoli. In kids necropsied late in the disease, these changes were accompanied by hyperplasia of type-II epithelial cells. Viral inclusions were not an obvious feature, but a few cells contained probable inclusions. CONCLUSIONS AND CLINICAL RELEVANCE: The caprine adenovirus reported here is capable of inducing respiratory tract disease and lesions in the lungs of young kids.

Distribution of anti-CD68 (EBM11) immunoreactivity in formalin-fixed, paraffin-embedded bovine tissues.

A commercially acquired anti-human macrophage antibody (anti-CD68; EBM11) was used in an immunocytochemical technique to detect macrophages in formalin-fixed, paraffin-embedded tissues from cattle, pigs, humans, rats, turkeys, dogs, and cats. In healthy cattle, the antibody labeled alveolar macrophages, pulmonary intravascular cells (presumably intravascular macrophages), and macrophage-like cells in other tissues. In bovine lungs infected with Pasteurella haemolytica, EBM11 antibody labeled 95% of alveolar macrophages and macrophages within alveolar septa but only 0-2% of streaming or "oat" leukocytes. Alveolar macrophages were also stained by EBM11 in pigs but not in rats, turkeys, dogs, and cats. The antibody also stained macrophage aggregates in the mesenteric lymph nodes and intestinal lamina propria of Mycobacterium paratuberculosis-infected cattle. This study shows that the anti-CD68 (EBM11) antibody is a useful marker of macrophages in normal bovine tissues or tissues from areas of acute or chronic inflammation that have been routinely processed. The study also adds strength to the growing evidence suggesting that streaming leukocytes seen in pneumonic pasteurellosis are neutrophils.

Infected cell types in ovine lung following exposure to bovine respiratory syncytial virus.

Sixteen adult sheep (ten females, six males obtained from a closed flock at National Animal Disease Center, Ames, IA) were experimentally infected with bovine respiratory syncytial virus strain 375 (BRSV), and lung tissues were stained for viral antigen. Two infected sheep were euthanatized at each of the following post-inoculation times: 12, 24, 36, 48, 72, 96, 144, and 192 hours. Lung, nasal turbinates, trachea, right cranial bronchial and mediastinal lymph nodes, liver, and spleen were collected for histologic evaluation. An indirect immunoperoxidase technique was performed on routine paraffin-embedded sections of lung tissue, trachea, turbinates, and bronchial and mediastinal lymph nodes to determine the location of the BRSV antigen. For lung tissue from each sheep 400 light microscopic fields at 160x magnification were examined for staining for BRSV antigen. Lung tissue was also collected for virus and bacterial isolation. Daily serum samples were taken for determination of anti-BRSV titers. Severe respiratory disease was not produced in any sheep. Bovine respiratory syncytial virus was isolated from lung tissue collected from all sheep up through 144 hours post-inoculation. At 12 hours post-inoculation (case No. 2) respiratory syncytial virus antigen was detected in bronchiolar epithelium and a mononuclear cell within an alveolar space. Lung tissue from the sheep necropsied between 24 and 144 hours post-inoculation (case Nos. 3-14) contained BRSV antigen in bronchiolar epithelium, type I pneumocytes, type II pneumocytes, alveolar macrophages, and mononuclear cells within alveolar spaces. Macrophages staining for viral antigen were rare. Bronchiolar and type I epithelial cells comprised the majority of infected cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of ethylenediaminetetraacetic acid, tetrasodium salt dihydrate (EDTA)-Tween 20 treatment versus protease digestion of formalin-fixed tissue sections for detection of bovine respiratory syncytial virus antigen in infected ovine lung.

The efficacy of protease and ethylenediaminetetraacetic acid, tetrasodium salt dihydrate (EDTA)-Tween 20 in unmasking bovine respiratory syncytial virus (BRSV) antigens in formalin-fixed lung tissue was compared using avidin-biotin immunoperoxidase procedure. Tissues were taken from experimentally infected lambs. BRSV antigen stained in both techniques. Treatment with EDTA-Tween 20 resulted in more intense staining of BRSV infected cells, more uniform cytoplasmic staining, less non-specific background, and superior cellular detail in comparison to protease digestion.

Cardiovascular responses of fetal guinea pig to norepinephrine.

A technique allowing the direct measurement of fetal heart rate and blood pressure in the guinea pig is described in detail. The basal heart rate and blood pressure measurements under both pentobarbital and methoxyflurane anesthesia are given. In comparison to the mother, the fetal cardiovascular system was less responsive to norepinephrine. This technique demonstrates the feasibility of using the guinea pig in fetal cardiovascular experimentation.

An assessment of the Alabama Smile Keeper school dental health education program.

An evaluation of the Alabama Smile Keeper Dental Health Education Program was necessary to determine if educating teachers to teach preventive dentistry improved the oral hygiene and knowledge of dental health of elementary schoolchildren. Four hundred seventy-five students at the Maxwell Air Force Base elementary school in grades 1 through 6 were tested using a series of written examinations and scores from a plaque index (Greene's OHI-S Index) before and after the education program. Levels of plaque were significantly reduced immediately after instruction and retention test scores were significantly lower four months later than preinstruction test scores. Written examinations proved that knowledge increased immediately after instruction and retention test scores were significantly better than preinstruction test scores.