The membrane attack complex-also known as C5b-9-is the end-product of the classical, lectin, and alternative complement pathways. It is thought to play an important role in the pathogenesis of... Show moreThe membrane attack complex-also known as C5b-9-is the end-product of the classical, lectin, and alternative complement pathways. It is thought to play an important role in the pathogenesis of various kidney diseases by causing cellular injury and tissue inflammation, resulting in sclerosis and fibrosis. These deleterious effects are, consequently, targeted in the development of novel therapies that inhibit the formation of C5b-9, such as eculizumab. To clarify how C5b-9 contributes to kidney disease and to predict which patients benefit from such therapy, knowledge on deposition of C5b-9 in the kidney is essential. Because immunohistochemical staining of C5b-9 has not been routinely conducted and never been compared across studies, we provide a review of studies on deposition of C5b-9 in healthy and diseased human kidneys. We describe techniques to stain deposits and compare the occurrence of deposits in healthy kidneys and in a wide spectrum of kidney diseases, including hypertensive nephropathy, diabetic nephropathy, membranous nephropathy, IgA nephropathy, lupus nephritis, C3 glomerulopathy, and thrombotic microangiopathies such as the atypical hemolytic uremic syndrome, vasculitis, interstitial nephritis, acute tubular necrosis, kidney tumors, and rejection of kidney transplants. We summarize how these deposits are related with other histological lesions and clinical characteristics. We evaluate the prognostic relevance of these deposits in the light of possible treatment with complement inhibitors. Show less
Purpose: The moving rectangle method is used to disentangle the contributions of rectangularization and life span extension to the increase in life expectancy. It requires the choice of an endpoint... Show morePurpose: The moving rectangle method is used to disentangle the contributions of rectangularization and life span extension to the increase in life expectancy. It requires the choice of an endpoint of the survival curve that approaches the maximum age at death. We examined the effect of choosing different end points on the outcomes of this method. Methods: For five developed countries, survival curves from age 50 years were constructed per calendar year from 1922 onward. Survival values of 0.1, 0.01, and 0.001 were chosen as end points of the survival curve, and the contributions of rectangularization and life span extension to the increase in life expectancy were calculated using the moving rectangle method. Results: The choice of different survival values as end points profoundly influenced the estimated contributions of rectangularization and life span extension to the increase in life expectancy. When choosing 0.001, rectangularization contributed most years, whereas when choosing 0.1, life span extension contributed most years. Conclusions: When the moving rectangle method is used to estimate the contributions of rectangularization and life span extension to the increase in life expectancy, its outcomes depend on the choice of the endpoint of the survival curve. Show less
In this thesis, senescence is measured in human populations according to its definition of an increase in the risks of dysfunction, disease, and death with chronological age. Part I of this thesis... Show moreIn this thesis, senescence is measured in human populations according to its definition of an increase in the risks of dysfunction, disease, and death with chronological age. Part I of this thesis investigates how a population__s senescence rate can be measured through the increase in mortality rate with age. Part II of this thesis investigates how senescence can be measured through the increase in morbidity - with a focus on cardiovascular disease - in a non-western population and thus be compared with the senescence process in western populations. Show less
