Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Jun 2007
ReviewGlomerular targets for autoantibodies in lupus nephritis--an apoptotic origin.
Systemic lupus erythematosus (SLE) is an autoimmune syndrome where different organs may individually or simultaneously be affected. Whether SLE is one disease entity or represents a variety of intrinsically unrelated organ manifestations is unknown. Variability of clinical presentations of SLE argues against the former. ⋯ It is believed that in situ binding of anti-dsDNA antibodies by nucleosomes is involved in organ manifestations in SLE. This review will focus on nature and origin of target structures for anti-dsDNA and antinucleosome antibodies in glomerular capillary and mesangial matrix membranes. We will particularly discuss the potential role of apoptosis and release of apoptotic chromatin in terms of their putative impact in SLE.
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Ann. N. Y. Acad. Sci. · Mar 2007
ReviewPhosphorylation and other conundrums of Na/Ca exchanger, NCX1.
The Na+/Ca2+ exchanger (NCX) is an important Ca2+ transport mechanism in virtually all cells in the body. There are three genes that control the expression of NCX in mammals. ⋯ Here we briefly discuss three remarkable regulatory issues or "conundrums" that involve the most prevalently expressed gene, NCX1. (1) How is NCX1 regulated by phosphorylation? We suggest that the macromolecular complex of NCX1 plays a critical role in the regulation of NCX. The role of the macromolecular complex and evidence supporting its existence and functional importance is presented. (2) Can there be transport block of a single "mode" of NCX1 transport by drugs or therapeutic agents? The simple answer is "no." A brief explanation is provided. (3) How can NCX1 knockout mice live? The answer is "by other compensatory regulatory mechanisms." These conundrums highlight important features in NCX1 and lay the foundation for new experiments to elucidate function and regulation of NCX1 and provide a context for investigations that seek to understand novel therapeutic agents.
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Ann. N. Y. Acad. Sci. · Feb 2007
ReviewShifting paradigms in dementia: toward stratification of diagnosis and treatment using MRI.
Atrophy and cerebrovascular disease are the two most important magnetic resonance imaging (MRI) characteristics in the evaluation of dementia. On MRI, atrophy is the primary hallmark of neurodegenerative dementias including Alzheimer's disease (AD), while vascular dementia is characterized by the presence of ischemic vascular damage, such as territorial infarcts, lacunes, and white matter hyperintensities. Evidence is accumulating that vascular factors play an important role in the development of cognitive decline at old age and clinical AD. ⋯ The strict distinction between AD and vascular dementia is often artificial, as most patients suffer from both disorders to some extent. For the future, we see an important role for MRI in identifying those different compartments, regardless of clinical classification. Treatment could be directed by (and evaluated through) MRI patterns, rather than a diagnostic label.
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Ann. N. Y. Acad. Sci. · Dec 2006
ReviewHormone replacement therapy and cardioprotection: what is good and what is bad for the cardiovascular system?
The incidence of cardiovascular diseases (CVDs) increases after menopause and at any age postmenopausal women have a significantly higher incidence of CVD compared to premenopausal women. Several epidemiological findings suggest the causative pathogenetic role of ovarian hormone deficiency in the development of CVD in women. Ovarian hormones have several potential protective effects on the cardiovascular system and despite several observational studies have shown the beneficial effect of estrogens and estrogen/progestin associations on CVD, at the present, after the findings of randomized studies, the effect of hormone replacement therapy (HRT) in the prevention of CVD is still under debate. ⋯ In early postmenopausal women, like the ones included in the observational studies, ovarian hormone replacement may be cardioprotective because of the responsiveness of the endothelium to estrogens that also buffer the detrimental effects upon coagulation. In late postmenopausal women ovarian hormones have either a null effect or even a detrimental effect because of the predominance of the procoagulant or plaque-destabilizing effects over the vasoprotective effects. Therefore, HRT has beneficial cardiovascular effects in younger women while it may have detrimental effect on coagulative balance and vascular inflammation and has little effect on cardiovascular functions in older women.
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During adolescence the brain shows remarkable changes in both structure and function. The plasticity exhibited by the brain during this pubertal period may make individuals more vulnerable to perturbations, such as stress. Although much is known about how exposure to stress and stress hormones during perinatal development and adulthood affect the structure and function of the brain, relatively little is known about how the pubertal brain responds to stress. ⋯ The purpose of this review is to present what is currently known about the pubertal maturation of the hypothalamic-pituitary-adrenal (HPA) axis, the neuroendocrine axis that mediates the stress response, and discuss what is currently known about how stressors affect the adolescent brain. Our dearth of knowledge regarding the effects of stress on the pubertal brain will be discussed in the context of our accumulating knowledge regarding stress-induced neuronal remodeling in the adult. Finally, as the adolescent brain is capable of such profound plasticity during this developmental stage, we will also explore the possibility of adolescence as a period of interventions and opportunities to mitigate negative consequences from earlier developmental insults.