http://hdl.handle.net/1956/931 Search the Channel search http://bora.uib.no/simple-search http://hdl.handle.net/1956/2219 Title: Uterine cervical neoplasia : aspects of biology and pathology <br/> <br/>Authors: Bertelsen, Bjørn I. http://hdl.handle.net/1956/2214 Title: Time-dependent clock gene expression in mouse and human stem and progenitor cells <br/> <br/>Authors: Tsinkalovsky, Oleg <br/> <br/>Abstract: Time is a fundamental part of all biological processes. During the whole process of evolution, living cells and organisms had to adapt to cyclic variations in the environment. In particular, the light and temperature conditions varied with day and night and with the seasons. The cellular functions and behavior in organisms were regulated according to their daily needs and provision of optimal conditions for survival. Time functions in cells are of two kinds. One is the cyclic variation, where the same events come back with regular intervals. Thereby, cellular adaptation occurs in a cyclic manner. The second way is longitudinal time regulation. From conception on, the development of organs occur sequentially and strictly coordinated in time until a mature fetus is ready for delivery. The periods of gestation, infant, growth and maturity, as well as aging, are strictly regulated in all higher organisms. Total life span is also rather constant within each species, although there are differences of many fold between short-lived and long-lived species. Thus, all the different longitudinal time periods in the life within a species are strictly coordinated to each other and are in concordance with total life span. Time regulation in single cells occurs at shorter intervals, both with cyclic and noncyclic variations. The oscillations may be down to a few seconds or even parts of seconds, such as nerve pulses. Heartbeat in higher organisms usually occurs as a rhythm of about one second or less, respiratory rhythm is slower, while the rhythm of the blood pressure is according to day and night. As a result, many types of time regulation and adaptation are occurring simultaneously in the same organism. Until a few years ago, the study of such time keeping was largely confined to the observation of phenomena from the outside and with mainly a descriptive approach. This has been replaced by a deeper understanding of the underlying biology and regulatory mechanisms at the genetic level (for recent review see Koukkari and Sothern, 2006b). This thesis deals with the hematopoietic system in mice and in men, a highly adaptable tissue with a high cell turnover and many different functions that cover all parts of the body. It is therefore no wonder that time keeping is an important part of the regulatory circuits. The main emphasis of this thesis is on the elucidation of local clock functions in cells of different stage of maturation, and discussion on how the molecular clock in bone marrow (BM) is unique compared to other tissues, as well as different between species. http://hdl.handle.net/1956/1926 Title: Polymorphisms of the XRCC1, XRCC3 and XPD genes and risk of colorectal adenoma and carcinoma, in a Norwegian cohort : a case control study <br/> <br/>Authors: Skjelbred, Camilla Furu; Sæbø, Mona; Wallin, Håkan; Nexø, Bjørn Andersen; Hagen, Per Christian; Lothe, Inger Marie Bowitz; Aase, Steinar; Johnson, Egil; Hansteen, Inger-Lise; Vogel, Ulla; Kure, Elin H. <br/> <br/>Abstract: Background: Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. Less is known about other DNA repair pathways in colorectal carcinogenesis. In this study we have focused on the XRCC1, XRCC3 and XPD genes, involved in base excision repair, homologous recombinational repair and nucleotide excision repair, respectively. Methods: We used a case-control study design (157 carcinomas, 983 adenomas and 399 controls) to test the association between five polymorphisms in these DNA repair genes (XRCC1 Arg194Trp, Arg280His, Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln), and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression model adjusting for age, gender, cigarette smoking and alcohol consumption. Results: The XRCC1 280His allele was associated with an increased risk of adenomas (OR 2.30, 95% CI 1.19–4.46). The XRCC1 399Gln allele was associated with a reduction of risk of high-risk adenomas (OR 0.62, 95% CI 0.41–0.96). Carriers of the variant XPD 751Gln allele had an increased risk of low-risk adenomas (OR 1.40, 95% CI 1.03–1.89), while no association was found with risk of carcinomas. Conclusion: Our results suggest an increased risk for advanced colorectal neoplasia in individuals with the XRCC1 Arg280His polymorphism and a reduced risk associated with the XRCC1 Arg399Gln polymorphism. Interestingly, individuals with the XPD Lys751Gln polymorphism had an increased risk of low-risk adenomas. This may suggest a role in regression of adenomas.