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A case of urothelial carcinoma in situ of urinary bladder is reported in a 10-year-old cow naturally grazing on bracken-infested land. The cow suffered from enzootic hematuria for more than 5 years. The presence of bovine papillomavirus type 2 (BPV-2) DNA sequences was detected by polymerase chain reaction. The carcinoma in situ was characterized by the presence of anaplastic cells with amphophilic cytoplasm and pleomorphic nuclei containing granular, irregularly dispersed chromatin. Focal areas within the tumor contained large isolated and/or clustered cells. These cells had pale acidophilic cytoplasm, large nuclei with single or multiple nucleoli, and well-defined borders resembling Paget's cells. Immunohistochemically, all malignant cells were negative for vimentin and S-100 and positive for cytokeratins. In addition, normal and neoplastic cells expressed fragile histidine triad (FHIT) protein; surprisingly, some pagetoid cells did not. FHIT, the tumor suppressor gene at 3p14.2, encodes a protein of 147 amino acids (16.8 kd) with diadenosine triphosphate hydrolase activity and is a common target of deletions in human cancers of epithelial origin. Antibody to laminin detected a continuous epithelial basement membrane, thus clearly showing that neoplastic changes were limited to urothelial cells without invading stromal tissue. To our knowledge, this is the first report of an unusual pattern of spread of urothelial carcinoma in situ in a cow.

Studies on children with cancer have suggested that energy expenditure may indeed be greater than predicted for healthy children. Nutritional assessment is important for intervention and for the prevention of complications associated with malnutrition. The present study aimed to describe the nutritional status, energy expenditure, and substrate utilization of children and adolescents with cancer compared to healthy children matched for age, sex, and body mass index. Subjects were evaluated by anthropometry, food intake pattern, and body composition analysis. Energy expenditure and substrate oxidation were measured by indirect calorimetry. Indirect calorimetry data, energy, and macronutrient intake, anthropometry, and body composition parameters showed no significant differences between groups. There was no evidence of increased energy expenditure or of a change in substrate utilization in children with cancer compared to the healthy group. The data regarding usual food consumption showed no significant differences between groups.

Abstract. Expression of uroplakins (UPs) was investigated in 20 bladder tumors from cows that had been suffering from chronic enzootic hematuria for several years. In dysplastic urothelium and papillomatous proliferations, UP expression was evident both as luminal and intercellular staining. Chronic enzootic hematuria is a clinical syndrome of cattle caused by prolonged ingestion of some toxic substances from bracken fern (Pteridium spp.). Epithelial and mesenchymal tumors of the urinary bladder are frequently associated with this syndrome. Uroplakins (UPs) are major specific urothelial differentiation products of mammalian urothelium. 5,10 They are mainly produced in cells of the superficial layer of transitional cell epithelium, and they consist of four components: the 27-kd UP Ia, the 28-kd UP Ib, the 15-kd UP II, and the 47-kd UP III. 12,13 UPs are conserved through a broad range of mammalian species and are the major protein components of the asymmetric unit membrane (AUM). 11 The AUM forms the apical plaques of mammalian urothelium 1 and may act as a permeability barrier; it also may act as a means of stabilizing the apical bladder surface. 9 It has been suggested that the ability of the urothelium to terminally differentiate is gradually lost in neoplastic processes, so UPs may be a useful morphologic biomarker of differentiation in bladder carcinogenesis. 14 The aim of the present study was to investigate UP expression immunohistochemically in spontaneous tumors of the urothelium in cows grazing on bracken fern-infested land in southern Italy. Materials and MethodsSamples of neoplastic urothelium were obtained at public slaughterhouses from twenty 4-16-year-old cows that had been suffering from chronic enzootic hematuria for several years. All the animals were known to have grazed on bracken-infested pasture because they were raised in mountain areas. Urothelium, uterus, vagina, fallopian tube, ovary, and mammary gland from five 4-14-year-old healthy cows were also examined as controls. These control animals came from lowlands, where bracken fern is virtually absent. Tissues were fixed in 10% buffered formalin and processed routinely for paraffin embedment. The avidin-biotin-peroxidase complex method was used for immunohistochemical analysis of UP. Immunofluorescence staining for confocal laser scanning microscopic investigations was also performed. Five-micrometer-thick sections were blocked for endogenous peroxidase in 0.3% H 2 O 2 in methanol for 20 minutes. Antigen was enhanced by pretreating with microwave heating (twice for 5 minutes each at 750 W). Anti-AUM antibody reacting with all four UPs (Dr. T. T. Sun, Epithelial Biology Unit, Ronald Perelman Department of Dermatology. Department of Pharmacology and Kaplan Comprehensive Cancer Center. New York University School of Medicine, New York, NY) was made against highly purified bovine AUM and applied overnight at 4 C at a 1 : 2,000 dilution. Slides were washed three times, incubated with secondary antibody (biotinylated goat anti-rabbit IgG, Dako, D...

Several immunohistochemical markers have been used to define the differentiation pattern of urothelial cell tumors of the urinary bladder. We investigated the expression of the recently characterized uroplakin (UP) IIIb, an urothelium-specific and differentiation-dependent protein, in 39 urothelial tumors of the urinary bladder in cows that had suffered from chronic enzootic hematuria for several years. Bovine papillomavirus type 2 DNA was amplified and UP IIIb protein was detected in all these tumors. In papillomas and papillary carcinomas, UP IIIb expression was mostly seen as superficial staining; luminal and peripheral patterns were also observed. In nonpapillary carcinomas, UP IIIb appeared to define clearly the cell membrane lining intercellular and intracellular lumina as well as the cell borders in deeper cell layers. In benign and malignant lesions, an intracytoplasmic immunoreactivity was also detected. Coarse intracytoplasmic UP IIIb-positive material close to the nucleus occurred in some malignant cells. Focally strong membraneous immunostaining that marked single cells with complete ringlike peripheral pattern was seen. Although UP IIIb expression does not seem to correlate with the biological behavior of urothelial tumors, it appears to be a highly sensitive marker for bovine urothelial tumors.