Cyclooxygenase-2 expression in inflammatory lung lesions of nonhuman primates.

Mammalian cells contain two related but unique isoforms of cyclooxygenase (COX-1 and COX-2). COX-1 is expressed constitutively in a majority of tissues and is involved in the production of prostaglandins (PGs) that modulate normal physiologic functions. COX-2 is inducible by various stimuli and is involved in the production of PGs that modulate physiologic events in development, cell growth, and inflammation. With the exception of peribronchial glands and chondrocytes of peribronchial cartilage, COX-2 is not detectable in the normal lung of nonhuman primates. We evaluated COX-2 expression by immunohistochemical methods in the inflammatory lesions of two cynomolgus monkeys (Macaca fascicularis) with acute severe pneumonia. Both monkeys exhibited acute severe bronchopneumonia; histologically, lung lesions were characterized by infiltration of large numbers of neutrophils and fewer macrophages, mild bronchial epithelial hyperplasia, and slight type-2 pneumocyte hyperplasia. In both monkeys, mild to marked COX-2 immunoreactivity was detected within the cytoplasm of macrophages, bronchial epithelial cells, type-2 pneumocytes, and endothelial cells of blood vessels. No COX-2 immunoreactivity was detectable in the neutrophils that constituted >90% of the inflammatory cells. These observations suggest that in acute inflammatory lung lesions in nonhuman primates 1) COX-2 is induced in the bronchial and alveolar epithelial cells, 2) macrophages are the primary inflammatory cells that exhibit COX-2, and 3) neutrophils do not express COX-2.

Expression of cyclooxygenase-2 in transitional cell carcinoma of the urinary bladder in dogs.

OBJECTIVE: To evaluate expression of cyclooxygenase (COX)-1 and COX-2 in the urinary bladder epithelium of clinically normal dogs and in transitional cell carcinoma cells of dogs. ANIMALS: 21 dogs with transitional cell carcinoma of the urinary bladder and 8 dogs with clinically normal urinary bladders. PROCEDURE: COX-1 and COX-2 were evaluated by use of isoform-specific antibodies with standard immunohistochemical methods. RESULT: COX-1, but not COX-2, was constitutively expressed in normal urinary bladder epithelium; however, COX-2 was expressed in neoplastic epithelium in primary tumors and in metastatic lesions of all 21 dogs and in new proliferating blood vessels in 3 dogs. Also, COX-1 was expressed in the neoplastic cells. CONCLUSIONS AND CLINICAL RELEVANCE: Lack of expression of COX-2 in normal bladder epithelium and its substantial expression in transitional cell carcinoma cells suggest that this isoform may be involved in tumor cell growth. Inhibition of COX-2 is a likely mechanism of the antineoplastic effects of non steroidal antiinflammatory drugs.

Respiratory and pharyngo-esophageal iridovirus infection in a gopher tortoise (Gopherus polyphemus).

A free-living adult male gopher tortoise (Gopherus polyphemus) was found on Sanibel Island, Florida (USA), on 18 February 1992 with signs of upper respiratory disease. On necropsy after euthanasia on 27 February 1992, severe, extensive necrotizing ulcerative tracheitis, multifocal necrotizing pneumonia, and multifocal necrotizing ulcerative pharyngitis and esophagitis were observed. Large ovoid to round intracytoplasmic basophilic inclusions, which appeared to displace the nucleus to the cell periphery, occurred within degenerate and necrotic epithelial cells of the above tissues. On transmission electron microscopy of formalin-fixed trachea and lung, intracytoplasmic viral particles were observed within necrotic cells in the tracheal lumen and epithelial cells of the lung. Most infected cells also had a roughly spherical granular cytoplasmic inclusion that contained clusters of viral particles. Viral particles had an electron dense spherical to icosahedral core surrounded by a less electron dense icosahedral capsid. Mature extracellular virions were surrounded by an envelope and were 150 to 220 nm in diameter. Virions and cytoplasmic inclusions were morphologically similar to those of the Family Iridoviridae.

Clinical and clinical laboratory correlates in sea otters dying unexpectedly in rehabilitation centers following the Exxon Valdez oil spill.

Following the Exxon Valdez oil spill, 347 oiled sea otters (Enhydra lutris) were treated in rehabilitation centers. Of these, 116 died, 94 within 10 days of presentation. Clinical records of 21 otters dying during the first 10 days of rehabilitation were reviewed to define the laboratory abnormalities and clinical syndromes associated with these unexpected deaths. The most common terminal syndrome was shock characterized by hypothermia, lethargy, and often hemorrhagic diarrhea. In heavily and moderately oiled otters, shock developed within 48 hours of initial presentation, whereas in lightly oiled otters shock generally occurred during the second week of captivity. Accompanying laboratory abnormalities included leukopenia with increased numbers of immature neutrophils (degenerative left shift), lymphopenia, anemia, azotemia (primarily prerenal), hyperkalemia, hypoproteinemia/hypoalbuminemia, elevations of serum transaminases, and hypoglycemia. Shock associated with hemorrhagic diarrhea probably occurred either as a direct primary effect of oiling or as an indirect effect secondary to confinement and handling in the rehabilitation centers. Lightly oiled otters were less likely to die from shock than were heavily oiled otters (22% vs. 72%, respectively). Heavily oiled otters developed shock more rapidly and had greater numbers of laboratory abnormalities, suggesting that exposure to oil was an important contributing factor.

Histopathologic lesions in sea otters exposed to crude oil.

Following the Exxon Valdez oil spill in Prince William Sound, Alaska, sea otters (Enhydra lutris) that appeared to be contaminated with oil, that were in danger of becoming contaminated, or that were behaving abnormally were captured and taken to rehabilitation centers. Exposure to oil was assessed by visual examination when otters arrived at the centers. Degree of oil exposure was graded according to the following criteria: oil covering greater than 60% of the body--heavily contaminated; oil covering 30-60% of the body--moderately contaminated; oil covering less than 30% of the body or light sheen on fur--lightly contaminated. If there was no oil visible, otters were considered uncontaminated. Tissues from 51 oil-contaminated sea otters (14 males, 37 females) and from six uncontaminated sea otters (three males, three females) that died in rehabilitation centers were examined histologically. Among oil-contaminated sea otters, 19/46 had interstitial pulmonary emphysema, 13/40 had gastric erosion and hemorrhage, 11/47 had centrilobular hepatic necrosis, 14/47 had periportal to diffuse hepatic lipidosis, and 10/42 had renal tubular lipidosis. Of the uncontaminated sea otters, 1/6 had gastric erosion and hemorrhage and 1/6 had diffuse hepatic lipidosis. Histologic examinations were performed on tissues from five sea otters (three males, two females) found dead with external oil present 15 to 16 days after the spill. Periportal hepatic lipidosis and renal tubular lipidosis were found in 3/5, and interstitial pulmonary emphysema was found in 1/5. Tissues from six apparently normal sea otters (four males, two females) collected from an area not affected by an oil spill were examined histologically, and none of these lesions were found. We conclude that interstitial pulmonary emphysema, centrilobular hepatic necrosis, and hepatic and renal lipidosis of sea otters were associated with exposure to crude oil. Gastric erosion and hemorrhage may have been associated with stress of captivity and/or oil exposure.

A histomorphologic and immunohistochemical study of chordoma in twenty ferrets (Mustela putorius furo).

The histomorphologic and immunohistochemical features of chordoma in 20 ferrets were evaluated. The mean age was 3.4 years, and, in the cases for which sex was known, females (n = 10) outnumbered males (n = 5) two to one. All 20 tumors occurred on the tip of the tail. Nineteen of 20 tumors (95%) were composed of three tissue components, often arranged concentrically with lobules of physaliferous cells at the periphery, trabecular bone in the center, and cartilage in between. The bone often contained marrow and hematopoietic cells. One tumor lacked chondromatous or osseous tissue. Immunohistochemical results were consistent with previous studies of chordoma. All 20 tumors (100%) were positive for keratin and vimentin intermediate filaments; 15 (75%) were positive for S-100 protein; and 17 (85%) were positive for neuron specific enolase. This neoplasm shares morphologic and immunohistochemical features with "classic," as well as chondroid chordoma, of human beings, making it a potential animal model.

Chronic upper respiratory tract disease of free-ranging desert tortoises (Xerobates agassizii).

Seventeen desert tortoises, Xerobates agassizii, with upper respiratory tract disease were examined; thirteen were euthanatized for necropsy. Four normal control desert tortoises from a clinically healthy population were similarly evaluated. Hemoglobin and phosphorus values were significantly (P less than or equal to 0.05) lower and serum sodium, urea, SGOT, and cholesterol values were significantly higher in ill tortoises compared to controls. No significant differences in concentrations of serum or liver vitamins A and E were found between the two groups. While no significant differences were found for concentrations of lead, copper, cadmium, and selenium, the livers of ill tortoises had higher concentrations of mercury and iron. Lesions were found consistently in the upper respiratory tract (URT) of ill tortoises. In all ill tortoises dense infiltrates of lymphocytes and histiocytes obscured the mucosal epithelium and underlying glands. The mucosal epithelium was variably dysplastic, hyperplastic, and occasionally ulcerated. Electron microscopic studies revealed small (350 to 900 nm), pleomorphic organisms resembling Mycoplasma sp., in close association with the surface epithelium of the URT of ill tortoises. Pasteurella testudinis was cultured from the nasal cavity of all ill tortoises and one of four control tortoises. A Mycoplasma sp. was cultured from the nasal passageways of four ill tortoises and was ultrastructurally similar to the pleomorphic organism present on the mucosa in tissue section.

Inhibition of malic enzyme by S-oxalylglutathione, a probable in vivo effector.

Various oxalyl thiol esters (RSCOCOO-), especially S-oxalylglutathione (GS-Ox), were found to be very effective inhibitors of chicken liver malic enzyme. When the conditions are similar to those encountered physiologically [high reduced nicotinamide adenine dinucleotide phosphate (NADPH) concentrations], inhibition is detectable with less than 1 microM concentrations of GS-Ox. The amount of inhibition is not reversed by excess glutathione, thus indicating that it is not due to oxalyl transfer to some enzymic thiol group with release of glutathione. Detailed kinetic studies show that the inhibition by GS-Ox can be treated as a simple reversible binding to the enzyme; the double reciprocal plot patterns indicate that the inhibition is linear noncompetitive (mixed type), vs. both L-malate in the oxidative decarboxylation reaction and pyruvate in the reverse reaction. At pH 7.4 and 25 degrees C in the presence of 100-200 microM NADPH, the Kis and Kii values for GS-Ox are 0.7 and 5 microM, respectively, and are the same for reactions run in either direction. The high specificity for GS-Ox is indicated by the observation that, under similar conditions, the Kis values for S-oxalyl coenzyme A and S-oxalyl-N-acetylcysteamine are 40 and 150 microM, respectively. Such high specificity indicates that the enzyme has evolved a specific binding site for the glutathione part of GS-Ox. The current results, when considered in conjunction with recent evidence that oxalyl thiol esters are present in animal tissues at concentrations up to 50 microM, imply that GS-Ox is an important in vivo regulator of malic enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)