Kanazawa Medical University

About: Kanazawa Medical University is a education organization based out in Kanazawa, Japan. It is known for research contribution in the topics: Population & Cancer. The organization has 3103 authors who have published 6322 publications receiving 144592 citations. The organization is also known as: Kanazawa ika daigaku.

Crystal Structure of Human 53BP1 Brct Domains Bound to P53 Tumour Suppressor

Abstract: The BRCT (BRCA1 C-terminus) is an evolutionary conserved protein–protein interacting module found as single, tandem or multiple repeats in a diverse range of proteins known to play roles in the DNA-damage response. The BRCT domains of 53BP1 bind to the tumour suppressor p53. To investigate the nature of this interaction, we have determined the crystal structure of the 53BP1 BRCT tandem repeat in complex with the DNA-binding domain of p53. The structure of the 53BP1–p53 complex shows that the BRCT tandem repeats pack together through a conserved interface that also involves the inter-domain linker. A comparison of the structure of the BRCT region of 53BP1 with the BRCA1 BRCT tandem repeat reveals that the interdomain interface and linker regions are remarkably well conserved. 53BP1 binds to p53 through contacts with the N-terminal BRCT repeat and the inter-BRCT linker. The p53 residues involved in this binding are mutated in cancer and are also important for DNA binding. We propose that BRCT domains bind to cellular target proteins through a conserved structural element termed the ‘BRCT recognition motif’.

Effect of shift work on body mass index and metabolic parameters.

Abstract: Objectives The aim of this cohort study was to investigate the effects of shift work on changes in parameters related to metabolic disturbances. Methods The study population included 1529 male blue-collar workers, aged 19–49 years at baseline, working in a sash and zipper factory in Japan. The participants were divided into four groups according to the work schedule at baseline, the end point being workers doing fixed daytime work in both years (day–day), workers who changed from shift work to fixed daytime work (shift–day), workers who changed from fixed daytime work to shift work (day–shift), and workers doing shift work in both years (shift–shift). The changes in body mass index (BMI), blood pressure, serum cholesterol, and glycosylated hemoglobin A1c over a period of 10 years were compared among the groups by work schedule. Results The age-adjusted mean increase in BMI was 1.03 kg/m 2 for the day–shift workers, and it was significantly larger than that of the day–day workers and shift–day workers. The shift–shift workers showed a significantly larger increase in BMI than the day–day workers. These tendencies remained after adjustment for age and all other confounding factors, such as BMI, smoking, drinking, and leisure-time physical activity at baseline. The increase in total cholesterol tended to be higher among the shift–shift workers and the day–shift workers, but there were no significant differences. Blood pressure and hemogrlobin A1c did not differ among the four groups. Conclusions Shift work is considered to be a risk factor for excess weight. However, no significant difference in the biomarkers was found between daytime workers and shift workers.

Septic Shock Is Associated with Receptor for Advanced Glycation End Products Ligation of LPS

Abstract: Septic shock is a severe systemic response to bacterial infection. Receptor for advanced glycation end products (RAGE) plays a role in immune reactions to recognize specific molecular patterns as pathogen recognition receptors. However, the interaction between LPS, the bioactive component of bacterial cell walls, and RAGE is unclear. In this study, we found direct LPS binding to RAGE by a surface plasmon resonance assay, a plate competition assay, and flow cytometry. LPS increased TNF-α secretion from peritoneal macrophages and an NF-κB promoter-driven luciferase activity through RAGE. Blood neutrophils and monocytes expressed RAGE, and TLR2 was counterregulated in RAGE−/− mice. After LPS injection, RAGE+/+ mice showed a higher mortality, higher serum levels of IL-6, TNF-α, high mobility group box 1, and endothelin-1, and severe lung and liver pathologies compared with RAGE−/− mice without significant differences in plasma LPS level. Administration of soluble RAGE significantly reduced the LPS-induced cytokine release and tissue damage and improved the LPS-induced lethality even in RAGE−/− as well as RAGE+/+ mice. The results thus suggest that RAGE can associate with LPS and that RAGE system can regulate inflammatory responses. Soluble RAGE would be a therapeutic tool for LPS-induced septic shock.

Mitotic Kinase Expression and Colorectal Cancer Progression

Abstract: Loss of chromosomal integrity as well as genomic stability is considered to act as a driving force during the processes of tumorigenesis and tumor progression(1–3). Recently, two kinase genes involved in mitosis, the genes for aurora and IPL1l ike midbodyassociated protein kinase-1 (4,5) [AIM1, registered in UniGene and also known as aurora1(6) and ARK2 (7)] and for serine/threonine kinase-6 [STK6, also known as BTAK/STK15(8,9),Aik (10), aurora2(6), and ARK1 (7)], which are related to Ipl1 inSaccharomyces cerevisiae and aurora inDrosophila, have been found to be expressed at high levels in cancer cells(5,6,9).These genes encode serine/threonine protein kinases whose functional roles during chromosomal segregation processes in mitosis have been examined (4–10). In transfected human cellsin vitro, the overexpression of either AIM-1 or STK6 causes chromosomal abnormalities, which are presumably attributed to a defect in the mitotic processes (5,9).Thus, these genes may be involved in the loss of chromosomal integrity during human cancer development via mitotic subversion.

Relation of Vegetable, Fruit, and Meat Intake to 7-Year Blood Pressure Change in Middle-aged Men The Chicago Western Electric Study

Abstract: Information is sparse on the role of foods in long-term blood pressure (BP) change. The investigators examined relations of food intake to BP change in a prospective cohort study of 1,710 employed men in Chicago, Illinois, initially aged 41-57 years. In 1958 and 1959, BP was measured and nutrient intake assessed by comprehensive interview. In 1959, intake of 26 specific food groups was also assessed. BP was remeasured annually through 1966. The generalized estimating equation method was used to analyze relations of food group intakes to average annual BP change, adjusting for age, weight at each year, alcohol consumption, calories, and other foods. Average systolic blood pressure (SBP)/diastolic blood pressure (DBP) increase was 1.9/0.3 mmHg per year. The SBP of men who consumed 14-42 cups of vegetables a month (0.5-1.5 cups/day) versus <14 cups a month (<0.5 cups/day) was estimated to rise 2.8 mmHg less in 7 years (p < 0.01). The SBP of men who consumed 14-42 cups of fruit a month versus <14 cups a month was estimated to increase 2.2 mmHg less in 7 years (p < 0.05). Beef-veal-lamb and poultry intakes were related directly to a greater SBP/DBP increase (p < 0.05). These results support the concept that diets higher in fruits and vegetables and lower in meats (except fish) may reduce the risk of developing high BP.