Genetic factors play an important role in the regulation of human life span but the exact pathways remain to be elucidated, however they may be interrelated with the regulation of human... Show moreGenetic factors play an important role in the regulation of human life span but the exact pathways remain to be elucidated, however they may be interrelated with the regulation of human reproduction. It is argued that an innate cytokine profile supportive of Th1-type T cells favors survival of infectious diseases (with longevity as the ultimate), but women with this profile are found less likely to have successful pregnancies (progeny). The probability of a normal fertility was found to increase more than 10-fold when the innate cytokine profile was characterized by high IL-10 (Th-2 cytokine) and low TNF- (Th-1 cytokine) responsiveness. The IL10 –2849 AA genotype was found to be associated with a decreased fertility and fecundity (time to pregnancy) in females, possibly due to the lower expected IL10 responsiveness. Rheumatoid arthritis (RA) is an example of a Th-1 mediated disease. It was found that the phenotype of joint destruction in RA was associated with the phenotype of reported miscarriages, suggesting common genetic risk factors for each of these two traits, possibly through the innate Th-1/Th-2 phenotype. Factor V Leiden (FVL) is a point mutation in the factor V gene generating a 7-fold increase in incidence of deep vein thrombosis. Specific advantages of the FVL mutation in early pregnancy (implantation) might balance its potentially harmful effects later in life and explain the remarkably high prevalence of this mutation in the general population. Show less
This thesis contains the results of several studies on the long-term consequences of the myeloablative conditioning for haematopoietic stem cell transplantation (SCT) during infancy and childhood,... Show moreThis thesis contains the results of several studies on the long-term consequences of the myeloablative conditioning for haematopoietic stem cell transplantation (SCT) during infancy and childhood, with the emphasis on late effects on endocrine functions. After a general introduction, effects of total-body irradiation (TBI) on pituitary and thyroid glands in rhesus monkeys and effects of irradiation on growth plates in growing rats are discussed. After these experimental animal data, effects of different conditioning regimens for SCT in children on growth, pubertal development, thyroid function and quality of life are discussed in subsequent chapters, and results of growth hormone therapy in these patients are presented. All study results presented in the thesis and relevant data from the literature are integrated into a general discussion at the end of the thesis. Show less
