Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Jun 2004
ReviewThe origin and functions of multiple human glucocorticoid receptor isoforms.
Glucocorticoid hormones are necessary for life and are essential in all aspects of human health and disease. The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR), which binds glucocorticoid hormones and regulates gene expression, cell signaling, and homeostasis. Decades of research have focused on the mechanisms of action of one isoform of GR, GRa. ⋯ We summarize here the processes that generate and modify various hGR isoforms with a focus on those that impact the ability of hGR to regulate target genes. We speculate that unique receptor compositions and relative receptor proportions within a cell determine the specific response to glucocorticoids. Unchecked expression of some isoforms, for example hGRbeta, has been implicated in various diseases.
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Ann. N. Y. Acad. Sci. · Jun 2004
ReviewFamilial/sporadic glucocorticoid resistance: clinical phenotype and molecular mechanisms.
Glucocorticoids regulate a variety of biologic processes and exert profound influences on many physiologic functions. Their actions are mediated by the glucocorticoid receptor (GR), which belongs to the nuclear receptor family of ligand-dependent transcription factors. Alterations in tissue sensitivity to glucocorticoids may manifest as states of resistance or hypersensitivity. ⋯ Compensatory elevations in circulating adrenocorticotropic hormone (ACTH) concentrations lead to increased production of adrenal steroids with mineralocorticoid and/or androgenic activity and their corresponding clinical manifestations, as well as increased urinary free-cortisol excretion in the absence of symptomatology suggestive of hypercortisolism. The molecular basis of the condition has been ascribed to mutations in the GR gene, which impair normal glucocorticoid signal transduction, altering tissue sensitivity to glucocorticoids. The present review focuses on the mechanisms of GR action and the clinical manifestations and molecular mechanisms of familial/sporadic glucocorticoid resistance.
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Ann. N. Y. Acad. Sci. · Jun 2004
Comparative StudyCell-free plasma DNA as a prognostic marker in intensive treatment unit patients.
Recent evidence suggests that cell-free plasma DNA has potential use as a prognostic marker in many clinical settings. The aim of the present study was to evaluate the prognostic role of cell-free plasma DNA in the prediction of clinical outcome in intensive treatment unit (ITU) patients. Cell-free plasma DNA was measured by real-time polymerase chain reaction assay for the beta-globin gene and SOFA score, APACHE II score, CRP concentrations, and clinical outcome (duration of stay, ventilation time, and mortality) were noted in 94 patients on admission to the ITU. ⋯ The median DNA concentration in nonsurvivors was 9148 GE/mL, and this was 2.3-fold greater than that in survivors (3921 GE/ml, P <0.001). ROC analysis of the data indicated a sensitivity of 85% and a specificity of 80% when DNA concentration of 6109 GE/mL was taken as a predictor of death. The data suggest that cell-free plasma DNA concentration is potentially useful as a prognostic marker in ITU patients.
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Ann. N. Y. Acad. Sci. · Jun 2004
Ultrasound as an alternative to aspiration for determining the nature of pleural effusion, especially in older people.
Sonography was performed by two expert radiologists separately after selecting 80 patients (45 men and 35 women) whose pleural fluids had been aspirated and examined by the lab. The radiologists were given no clinical information concerning the patients, and the result compared with lab results. The radiologists evaluated three criteria in determining the nature of the pleural effusion: septation, echogenicity, and thickening of pleura by more than 3 mm. ⋯ The lab results showed that there were 29 patients with transudates and 51 with exudates, and in ultrasound results there were 34 with transudates and 46 with exudates. A transudate is always without echogenicity, while exudates can be with or without echogenicity. It was therefore concluded that sonography is useful in determining the nature of pleural effusion.
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Ann. N. Y. Acad. Sci. · Jun 2004
Detection and characterization of circulating microsatellite-DNA in blood of patients with breast cancer.
Increased levels of circulating DNA have been reported in the blood of cancer patients but not healthy individuals. Tumor-specific genomic aberrations, such as loss of heterozygosity (LOH) and microsatellite instability (MSI), can be detected in this free extracellular DNA. Identification of these genetic aberrations may play an important role in cancer diagnosis and prediction of disease progression. ⋯ In conclusion, genomic aberrations on chromosomes 10, 16, and 17 are frequent in the circulating DNA of breast cancer patients. However, circulating tumor DNA does not reflect the presence of tumor cells in blood or the level of tumor-associated protein markers such as CA 15-3. Thus, screening for circulating tumor DNA may provide additional diagnostic information.