Annals of the New York Academy of Sciences
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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.
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Ann. N. Y. Acad. Sci. · Jun 2004
ReviewSeasonal plasticity in the song control system: multiple brain sites of steroid hormone action and the importance of variation in song behavior.
Birdsong, in non-tropical species, is generally more common in spring and summer when males sing to attract mates and/or defend territories. Changes in the volumes of song control nuclei, such as HVC and the robust nucleus of the arcopallium (RA), are observed seasonally. Long photoperiods in spring stimulate the recrudescence of the testes and the release of testosterone. ⋯ Testosterone can act via brain-derived neurotrophic factor (BDNF) that is also released in HVC as a result of song activity. Testosterone could enhance song nucleus volume indirectly by acting in the preoptic area, a region regulating sexual behaviors, including song, that connects to the song system through catecholaminergic cells. Seasonal neuroplasticity in the song system involves an interplay among seasonal state, testosterone action, and behavioral activity.
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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.