RESUMO
A 56-year-old woman with Langerhans cell histiocytosis of the petrous bone presented with sudden onset of sensorineural hearing loss and vertigo without other neurological impairment, mimicking idiopathic sudden sensorineural hearing loss. Differential diagnosis was difficult until neuroimaging demonstrated a lesion of the petrous bone. The patient eventually underwent removal of the lesion via the transpetrosal approach, and received postoperative chemotherapy consisting of vinblastine, methotrexate, 6-mercaptopurine, and prednisolone. Although her hearing did not recover, complete remission was achieved, and the patient is currently free from disease. Physicians need to be aware that patients with sudden onset of hearing loss may have an unexpected and hidden disease which requires neuroimaging and histological examinations for definitive diagnosis and appropriate treatment.
Assuntos
Doenças Ósseas/complicações , Perda Auditiva Neurossensorial/etiologia , Histiocitose de Células de Langerhans/complicações , Osso Petroso/patologia , Vertigem/etiologia , Doença Aguda , Doenças Ósseas/patologia , Doenças Ósseas/terapia , Quimioterapia Combinada , Feminino , Perda Auditiva Neurossensorial/patologia , Histiocitose de Células de Langerhans/patologia , Histiocitose de Células de Langerhans/terapia , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Vertigem/patologiaRESUMO
BACKGROUND: Our previous studies of the transcriptional regulation of the human ABO gene indicated that negative regulatory elements are present in the sequence just upstream from the proximal promoter. The role of the -275 to -118 region in regulation of ABO gene transcription is further characterized. STUDY DESIGN AND METHODS: Transient transfection experiments into various cells were performed with luciferase reporter plasmids carrying ABO upstream sequences, and electrophoretic mobility shift assay was carried out with a nuclear extract prepared from the human gastric cancer KATOIII cells. RESULTS: It is shown that the -202 to -118 region is involved in the negative regulation of ABO gene transcription in all cell lines examined. Transient transfection experiments in KATOIII cells with a reporter plasmid carrying mutated N box at -196 to -191 demonstrate that the N box is a negative regulatory element in the -202 to -118 sequence. Electrophoretic mobility shift assays indicate that the N box binds with a nuclear factor from KATOIII cells. CONCLUSION: These results indicate that repression of transcription from the ABO proximal promoter is partially dependent upon the N box. Therefore, reduced binding of the protein with the N box might play a direct role in ABO gene expression.
Assuntos
Sistema ABO de Grupos Sanguíneos/genética , Regulação da Expressão Gênica , Regiões Promotoras Genéticas , Transcrição Gênica , Sequência de Bases , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/fisiologia , Genes Reguladores , Humanos , Dados de Sequência Molecular , Fatores de Transcrição/fisiologiaRESUMO
We have studied the expression of human histo-blood group ABO genes during erythroid differentiation, using an ex vivo culture of AC133(-)CD34(+) cells obtained from peripheral blood. 5'-Rapid amplification of cDNA ends analysis of RNA from those cells revealed a novel transcription start site, which appeared to mark an alternative starting exon (1a) comprising 27 bp at the 5'-end of a CpG island in ABO genes. Results from reverse transcription-PCR specific to exon 1a indicated that the cells of both erythroid and epithelial lineages utilize this exon as the transcription starting exon. Transient transfection experiments showed that the region just upstream from the transcription start site possesses promoter activity in a cell type-specific manner when placed 5' adjacent to the reporter luciferase gene. Results from bisulfite genomic sequencing and reverse transcription-PCR analysis indicated that hypermethylation of the distal promoter region correlated with the absence of transcripts containing exon 1a, whereas hypermethylation in the interspersed repeats 5' adjacent to the distal promoter was commonly observed in all of the cell lines examined. These results suggest that a functional alternative promoter is located between the hypermethylated region of repetitive elements and the CpG island in the ABO genes.