Promoter methylation and silencing of the retinoic acid receptor-beta gene in lung carcinomas.

BACKGROUND: Retinoic acid plays an important role in lung development and differentiation, acting primarily via nuclear receptors encoded by the retinoic acid receptor-beta (RARbeta) gene. Because receptor isoforms RARbeta2 and RARbeta4 are repressed in human lung cancers, we investigated whether methylation of their promoter, P2, might lead to silencing of the RARbeta gene in human lung tumors and cell lines. METHODS: Methylation of the P2 promoter from small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cell lines and tumor samples was analyzed by the methylation-specific polymerase chain reaction (PCR). Expression of RARbeta2 and RARbeta4 was analyzed by reverse transcription-PCR. Loss of heterozygosity (LOH) was analyzed by PCR amplification followed by electrophoretic separation of PCR products. Statistical differences were analyzed by Fisher's exact test with continuity correction. RESULTS: The P2 promoter was methylated in 72% (63 of 87) of SCLC and in 41% (52 of 127) of NSCLC tumors and cell lines, and the difference was statistically significant (two-sided P:<.001). By contrast, in 57 of 58 control samples, we observed only the unmethylated form of the gene. Four tumor cell lines with unmethylated promoter regions expressed both RARbeta2 and RARbeta4. Four tumor lines with methylated promoter regions lacked expression of these isoforms, but demethylation by exposure to 5-aza-2'-deoxycytidine restored their expression. LOH at chromosome 3p24 was observed in 100% (13 of 13) of SCLC lines and 67% (12 of 18) of NSCLC cell lines, and the difference was statistically significant (two-sided P: =.028). CONCLUSIONS: Methylation of the RARbeta P2 promoter is one mechanism that silences RARbeta2 and RARbeta4 expression in many lung cancers, particularly SCLC. Chemical demethylation is a potential approach to lung cancer therapy.

Developing a health information network within an integrated delivery system: a case study.

Changes in the health care environment, such as the growth of integrated delivery systems and the proliferation of managed care, are having a profound impact on the way in which health care organizations manage both clinical and financial information. Health information networks (HINs) are emerging to support the goals and internal needs of integrated delivery systems. In this environment, health care managers must assume a leadership role in planning for the development of HINs. The article provides an overview of the principal issues that should be addressed in an organization's information systems plan when a HIN is being developed and includes a case study that illustrates the key points discussed.

Clinical information systems: 25-year history and the future.

Clinical information Systems have not advanced rapidly enough to meet the growing needs for clinical data. This is due primarily to the industry's past focus on financial information processing. Pressure is increasing for clinical data to support health-care professionals in the delivery of patient care, and in the establishment and monitoring of quality of care indicators. This article summarizes the history of clinical systems, and presents key issues regarding future clinical information systems.

Service unit management and nurses' satisfaction.

Nurses' satisfaction was compared in 55 patient units, 32 with service unit management (SUM) and 23 without. Satisfaction of licensed practical nurses was unrelated to SUM, but intrinsic task satisfaction of registered nurses (and of head nurses, who were considered separately) was positively related to the presence of SUM. Transfer of nonprofessional tasks out of nursing and reduction of tension arising from reduced responsibility of nurses for coordinating activities with ancillary departments are possible explanations for the positive relation between the presence of SUM and professional nurses' satisfaction.