We previously identified a gene, nuclear receptor-interaction protein (NRIP), which functions as a transcription cofactor in glucocorticoid receptor (GR) and human papillomavirus E2 (HPV E2)-driven gene expression. Here, we comprehensively evaluated the role of NRIP in HPV-16 gene expression. NRIP acts as a transcription cofactor to enhance GR-regulated HPV-16 gene expression in the presence of hormone. NRIP also can form complex with E2 that caused NRIP-induced HPV gene expression via E2-binding sites in a hormone-independent manner. Furthermore, NRIP can associate with GR and E2 to form tri-protein complex to activate HPV gene expression via GRE, not the E2-binding site, in a hormone-dependent manner. These results indicate that NRIP and GR are viral E2-binding proteins and that NRIP regulates HPV gene expression via GRE and/or E2 binding site in the HPV promoter in a hormone-dependent or independent manner, respectively.
Background Carbamazepine has been associated with severe cutaneous adverse drug reactions (ADR). It is important for patients with these ADRs under off-label prescriptions are not eligible for drug injury relief in Taiwan. We conducted a study to depict the demography and possible factors related to the off-label carbamazepine use in Taiwan. We also explored the policy influence of carbamazepine use. Methods We used the dataset of one million randomly-sampled insured persons in the Taiwan National Health Insurance Research Database for 2002 and 2006 to conduct a cross-sectional study. With the use of a computerized clinical information system, carbamazepine prescriptions were categorized into five groups (A, B, C, D and E) according to these indications: Group A, B were defined as on-label use; group C, D and E were defined as various levels of off-label use, depending on the strength of support from the literature. A logistic regression model was conducted to find the factors related to off-label use.Results Based on the one million representative samples, 6305 and 5703 patients received 31 146 and 27 579 carbamazepine prescriptions in 2002 and 2006 respectively. In both years, nearly 43% of total prescriptions were related to on-label uses. Prescriptions from primary clinics and departments of internal medicine and psychiatry, the physician's age, and the patient's age were factors associated with higher risk of off-label carbamazepine use. Conclusions Our study echoes the highly prevalent off-label use of carbamazepine in Taiwan and adds to the rare research on this subject in the East Asian population. The carbamazepine relabelling in 2004 did not change either prescription patterns or factors related to off-label use.
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