Immunohistochemical localization of NAD(P)H:quinone oxidoreductase in conjunctival melanomas and primary acquired melanosis.

PURPOSE: Mitomycin C has been used in the treatment of primary acquired melanosis and melanomas of the conjunctiva. Because there is increasing evidence that NAD(P)H:quinone oxidoreductase (EC 1.6.99.2, NQO1) or DT-diaphorase plays an important role in the bioactivation of mitomycin C, we examined pathologic specimens of these tumors for NQO1 by immunohistochemistry. METHODS: Formalin-fixed, paraffin-embedded sections with histologic diagnoses of primary acquired melanosis or conjunctival melanomas were obtained from the Eye Pathology Laboratory, University of Colorado Health Sciences Center. Detection of NQO1 in tissues was performed using standard immunohistochemical techniques with monoclonal antibodies against NQO1 and immunoperoxidase staining. Samples were examined by two independent reviewers and NQO1 staining was graded from 0 (no staining) to 3+ (intense staining). RESULTS: Eleven of 11 melanomas (95% confidence interval, 72% to 100%) and three of three lesions with primary acquired melanosis with atypia stained positively for NQO1. In the melanomas, staining was relatively uniform, while in primary acquired melanosis there was cell-to-cell variability in the staining. CONCLUSIONS: NQO1 was detected by immunohistochemistry in every examined section of primary acquired melanosis and melanoma of the conjunctiva, suggesting that NQO1 may play a role in the bioactivation of mitomycin C in these tumors.

Immunohistochemical localization of NQO1 in epithelial dysplasia and neoplasia and in donor eyes.

PURPOSE: To examine the expression of NAD(P)H:quinone oxidoreductase 1 (NQO1, DT-diaphorase), a potential bioactivating enzyme for mitomycin C in corneal and conjunctival epithelial dysplasia and neoplasia and in normal tissues from human donor eyes, by immunohistochemistry. METHODS: Formalin-fixed, paraffin-embedded sections of human donor eyes and tissue sections with histologic diagnoses of corneal and conjunctival epithelial dysplasia and neoplasia from the Eye Pathology Laboratory, University of Colorado Health Sciences Center were analyzed. Detection of NQO1 in tissues was performed using standard immunohistochemical techniques with monoclonal antibodies against NQO1 and immunoperoxidase staining. RESULTS: All 20 tumors stained positive for NQO1. In seven eyes from four donors, positive staining for NQO1 was detected in all epithelial and endothelial layers, in fibroblasts, in all retinal layers except the photoreceptor outer segments, and in the fascicles and arachnoid of the optic nerve. Only minimal staining was detected in the photoreceptor outer segments and the optic nerve pia and dura. Immunostaining was markedly reduced in all tissues in both eyes from donor 5. Genetic analysis confirmed that this individual was homozygous for a polymorphism in NQO1 (NQO1*2). CONCLUSIONS: NQO1 was detected by immunohistochemistry in every examined section of corneal and conjunctival epithelial dysplasia and neoplasia, suggesting that NQO1 may play a role in the bioactivation of mitomycin C in these tumors. However, the presence of NQO1 in the corneal, conjunctival, and ciliary epithelium; the retinas; and the optic nerves of donor eyes may indicate the potential for mitomycin C toxicity, particularly at higher doses.

Immunoglobulin A and immunoglobulin G biclonal gammopathy in a dog with multiple myeloma.

A nine-year-old golden retriever was referred for evaluation of chronic anorexia, vomiting, and diarrhea. Low body weight, mucous membrane pallor, and palpably enlarged liver and spleen were detected by physical examination. Anemia, hyperglobulinemia, and concurrent trichuriasis and coccidiosis were identified upon initial diagnostic evaluation. Punctate vertebral lysis was apparent radiographically. Atypical plasma cell proliferation was found in the bone marrow, liver, and spleen. An immunoglobulin A and immunoglobulin G biclonal gammopathy was demonstrated by serum protein electrophoresis and immunoelectrophoresis. The dog was diagnosed with multiple myeloma and euthanized per owner request. Multiple myeloma should be considered in the differential diagnosis for biclonal gammopathy in the dog.

Onchocerciasis in two dogs.

Although widely reported in cattle, horses, and other ungulates, onchocerciasis has only recently been reported in 1 dog. We report 2 additional dogs with onchocerciasis involving the palpebral conjunctiva, third palpebra, and sclera. Both dogs were evaluated because of ocular or periocular masses. Histologically, viable adult parasites were surrounded by minimal fibrosis and few macrophages. Pyogranulomas were often centered around degenerating or mineralized Onchocerca organisms. Onchocerciasis should be considered in the differential diagnosis of ocular or periocular nodules in dogs, particularly dogs from western states.

Kochia (Kochia scoparia) toxicosis in cattle: results of four experimental grazing trials.

Four kochia grazing trials were completed over a period of 3 years. Yearling steers were allowed to graze pure stands of irrigated and fertilized kochia (Kochia scoparia) for periods of 14 to 105 days. A total of 116 steers were given kochia as their sole forage. Twenty control steers were allowed to graze native grass pasture, and 20 steers were allowed to graze both native grass and kochia pastures. Steers grazing only kochia lost weight or gained poorly compared with control steers grazing native grass. Steers that grazed both kochia and native grass had intermediate rates of gain. Signs of toxicosis were observed only in steers grazing kochia alone. Considerable variability in the degree of toxicosis was observed from one year to another. Morbidity in the steers grazing only kochia varied from 0% (Trial 4) to 28% (Trial 1), and mortality varied from 0% (Trials 3 and 4) to 10% (Trial 2). The most common signs observed in clinically affected steers were depression, dehydration, weight loss, muscular weakness, photosensitization, ocular discharge, and crusty muzzle. In all 4 trials, significant elevations in serum glutamic oxaloacetic transaminase (GOT) and serum gamma glutamyl transpeptidase (GGT) were observed in steers grazing kochia. In 3 of the 4 trials, significant elevations in serum bilirubin, serum calcium, and serum protein were also observed in kochia-fed steers. Necropsies were performed on 6 of 9 steers that died or were euthanized. The primary pathologic findings were severe chronic nephrosis (5 steers) and degenerative hepatopathy (5 steers).(ABSTRACT TRUNCATED AT 250 WORDS)