ABSTRACT
The human homolog of KET, p63, bears strong homology to the tumor suppressor p53 and plays an essential role in epithelial development. CUSP, the most abundant cutaneous product of p63, has been identified as an autoantigen in chronic ulcerative stomatitis (CUS). The original report of KET expression at least partially contradicts p63 expression subsequently reported by many different groups. We have examined p63 expression by Northern analysis of RNA from multiple human tissues and by indirect immunofluorescence of rat tissue with CUS patient sera. Northern analysis reveals p63 RNA in skin, thymus, placenta, skeletal muscle, kidney, and lung, with non-transactivating p63 RNA in skin, thymus, and placenta. Reverse transcriptase polymerase chain reaction (rtPCR) assays show abundant non-transactivating p63 RNA, and little to no transactivating p63 RNA, in human basal cell carcinoma as well as in normal skin adjacent to the tumors. p63 RNA expression was not detected in brain, heart, colon, spleen, liver, or small intestine. Immunofluorescence reveals p63 expression in skin, oral epithelium, tongue, kidney, and trachea, but not in liver, large intestine, testis, skeletal muscle, or heart. Focal p63 expression within tissues, the complex array of isoforms encoded by the gene, and the specificity of the probes and antibodies utilized, may all contribute to contradictory accounts of CUSP/p63 expression.
Subject(s)
Genes, Tumor Suppressor , Gingivitis, Necrotizing Ulcerative/genetics , Membrane Proteins , Phosphoproteins/genetics , Trans-Activators/genetics , Transcription, Genetic , Tumor Suppressor Protein p53 , Animals , DNA-Binding Proteins , Female , Fluorescent Antibody Technique, Indirect , Genetic Variation , Humans , Kidney/metabolism , Male , Mouth Mucosa/metabolism , Organ Specificity , Phosphoproteins/analysis , RNA, Messenger/genetics , Rats , Skin/metabolism , Tongue/metabolism , Trachea/metabolism , Trans-Activators/analysis , Transcription Factors , Tumor Suppressor ProteinsABSTRACT
A unique clinical syndrome has been described in which patients have chronic oral ulceration and autoantibodies to nuclei of stratified squamous epithelium. We have characterized the autoantibodies from patients sera and found that the major autoantigen is a 70 kDa epithelial nuclear protein. Sequencing of the cDNA for this protein, chronic ulcerative stomatitis protein, revealed it to be homologous to the p53 tumor suppressor and to the p73 putative tumor suppressor, and to be a splicing variant of the KET gene. The p53-like genes, p73 and the several KET splicing variants, are recently described genes of uncertain biologic and pathologic significance. This study provides the first clear association of a p53-like protein with a disease process.
Subject(s)
Autoantigens/blood , Gingivitis, Necrotizing Ulcerative/blood , Gingivitis, Necrotizing Ulcerative/immunology , Autoantigens/genetics , Base Sequence , Binding Sites, Antibody , Cell Nucleus/chemistry , Fluorescent Antibody Technique , Genes, p53 , Humans , Keratinocytes/immunology , Keratinocytes/ultrastructure , Molecular Sequence Data , Sequence Homology, Amino AcidABSTRACT
In a study population of black Africans with advanced glaucoma in Ghana we conducted a prospective study of intraoperative 5-fluorouracil alone. Eyes undergoing trabeculectomy were randomly selected either to receive or not receive a single intraoperative application of 5-fluorouracil (50 mg/ml for five minutes). Fifty-five eyes had a mean follow-up of 282 days (minimum, 92 days). Twenty of 24 eyes (83%) in the 5-fluorouracil group vs 12 of 31 eyes (39%) in the control group had postoperative intraocular pressure of 20 mm Hg or less with or without medical therapy (P = .01). Eleven of 24 eyes (46%) in the 5-fluorouracil group and five of 31 eyes (16%) in the control group had intraocular pressure of 15 mm Hg or less (P = .02). Without medical therapy, 17 of 24 eyes (71%) in the 5-fluorouracil group and ten of 31 eyes (32%) in the control group had intraocular pressure of 20 mm Hg or less (P = .02). The overall complications were similar in the two groups. In this population, intraoperative 5-fluorouracil markedly improved the ability of trabeculectomy to lower intraocular pressure. We recommend that intraoperative 5-fluorouracil be considered in glaucoma surgery with poor prognosis as an alternative to postoperative subconjunctival injections when multiple injections are not feasible.
