Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The late radiation response of the heart is of concern because of many reports of heart disease following radiation therapy of thoracic tumors. This study was done because of the clinical relevance of the pathophysiology of cardiopulmonary irradiation and because the heart is a good model for late effects of vasculoconnective tissue due to its lack of acutely responding parenchymal cells. Thoracic irradiation of adult beagle dogs including the heart and one third of the lung volume produced an early response in the heart at 1 and 3 months which consisted of an increase in left ventricle and septal wall thickness, decreased left ventricle ejection fraction, increased heart rates, intraventricular conduction disturbances and a high probability for pericardial effusion at 3 months. Radiation doses were 36, 44, or 52 Gy given in 4 Gy fractions in 4 weeks. Premature atrial contractions, paroxysmal atrial tachycardia, sustained atrial tachycardia and atrial fibrillation occurred at all dose levels. Evidence suggests that both early and late responses were due, at least in part, to direct injury to the cardiac microvasculature. The later effects appeared to be enhanced by injury to the lung. The early response appeared to resolve in 6 to 9 months, after which there was thinning of the myocardium at higher doses and resolution of pericardial effusions. At 12 months, elevations in right atrial pressure, but not pulmonary wedge pressure, were suggestive of right-sided congestive heart failure. Pulmonary hypertension was also present at 12 months presumably due to partial lung irradiations, and may have exacerbated right-sided congestive heart failure. The radiation injury may continue to increase with time leading to serious deficits in cardiopulmonary function. The functional studies may aid in predicting late effects and evaluating residual injury.
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PMID:Canine cardiomyopathy after whole heart and partial lung irradiation. 338 19

Human cortical thickness and surface area are genetically independent, emerge through different neurobiological events during development, and are sensitive to different clinical conditions. However, the relationship between changes in the two over time is unknown. Additionally, longitudinal studies have almost invariably been restricted to older adults, precluding the delineation of adult life span trajectories of change in cortical structure. In this longitudinal study, we investigated changes in cortical thickness, surface area, and volume after an average interval of 3.6 years in 207 well screened healthy adults aged 23-87 years. We hypothesized that the relationships among metrics are dynamic across the life span, that the primary contributor to cortical volume reductions in aging is cortical thinning, and that magnitude of change varies with age and region. Changes over time were seen in cortical area (mean annual percentage change [APC], -0.19), thickness (APC, -0.35), and volume (APC, -0.51) in most regions. Volume changes were primarily explained by changes in thickness rather than area. A negative relationship between change in thickness and surface area was found across several regions, where more thinning was associated with less decrease in area, and vice versa. Accelerating changes with increasing age was seen in temporal and occipital cortices. In contrast, decelerating changes were seen in prefrontal and anterior cingulate cortices. In conclusion, a dynamic relationship between cortical thickness and surface area changes exists throughout the adult life span. The mixture of accelerating and decelerating changes further demonstrates the importance of studying these metrics across the entire adult life span.
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PMID:Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change. 2494 4

Mast cells (MCs) are the initial responders of innate immunity and their degranulation contribute to various etiologies. While the abundance of MCs in the choroid implies their fundamental importance in the eye, little is known about the significance of MCs and their degranulation in choroid. The cause of geographic atrophy (GA), a progressive dry form of age-related macular degeneration is elusive and there is currently no therapy for this blinding disorder. Here we demonstrate in both human GA and a rat model for GA, that MC degranulation and MC-derived tryptase are central to disease progression. Retinal pigment epithelium degeneration followed by retinal and choroidal thinning, characteristic phenotypes of GA, were driven by continuous choroidal MC stimulation and activation in a slow release fashion in the rat. Genetic manipulation of MCs, pharmacological intervention targeting MC degranulation with ketotifen fumarate or inhibition of MC-derived tryptase with APC 366 prevented all of GA-like phenotypes following MC degranulation in the rat model. Our results demonstrate the fundamental role of choroidal MC involvement in GA disease etiology, and will provide new opportunities for understanding GA pathology and identifying novel therapies targeting MCs.
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PMID:A role for mast cells in geographic atrophy. 3252 94