University of Milan

About: University of Milan is a education organization based out in Milan, Italy. It is known for research contribution in the topics: Population & Medicine. The organization has 58413 authors who have published 139784 publications receiving 4636354 citations. The organization is also known as: Università degli Studi di Milano & Statale.

Gallbladder cancer worldwide: geographical distribution and risk factors.

Abstract: Gallbladder cancer is a relatively rare neoplasm that shows, however, high incidence rates in certain world populations. The interplay of genetic susceptibility, lifestyle factors and infections in gallbladder carcinogenesis is still poorly understood. Age-adjusted rates were calculated by cancer registry-based data. Epidemiological studies on gallbladder cancer were selected through searches of literature, and relative risks were abstracted for major risk factors. The highest gallbladder cancer incidence rates worldwide were reported for women in Delhi, India (21.5/100,000), South Karachi, Pakistan (13.8/100,000) and Quito, Ecuador (12.9/100,000). High incidence was found in Korea and Japan and some central and eastern European countries. Female-to-male incidence ratios were generally around 3, but ranged from 1 in Far East Asia to over 5 in Spain and Colombia. History of gallstones was the strongest risk factor for gallbladder cancer, with a pooled relative risk (RR) of 4.9 [95% confidence interval (CI): 3.3-7.4]. Consistent associations were also present with obesity, multiparity and chronic infections like Salmonella typhi and S. paratyphi [pooled RR 4.8 (95% CI: 1.4-17.3)] and Helicobacter bilis and H. pylori [pooled RR 4.3 (95% CI: 2.1-8.8)]. Differences in incidence ratios point to variations in gallbladder cancer aetiology in different populations. Diagnosis of gallstones and removal of gallbladder currently represent the keystone to gallbladder cancer prevention, but interventions able to prevent obesity, cholecystitis and gallstone formation should be assessed.

DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1

Abstract: A single double-strand break (DSB) induced by HO endonuclease triggers both repair by homologous recombination and activation of the Mec1-dependent DNA damage checkpoint in budding yeast. Here we report that DNA damage checkpoint activation by a DSB requires the cyclin-dependent kinase CDK1 (Cdc28) in budding yeast. CDK1 is also required for DSB-induced homologous recombination at any cell cycle stage. Inhibition of homologous recombination by using an analogue-sensitive CDK1 protein results in a compensatory increase in non-homologous end joining. CDK1 is required for efficient 5' to 3' resection of DSB ends and for the recruitment of both the single-stranded DNA-binding complex, RPA, and the Rad51 recombination protein. In contrast, Mre11 protein, part of the MRX complex, accumulates at unresected DSB ends. CDK1 is not required when the DNA damage checkpoint is initiated by lesions that are processed by nucleotide excision repair. Maintenance of the DSB-induced checkpoint requires continuing CDK1 activity that ensures continuing end resection. CDK1 is also important for a later step in homologous recombination, after strand invasion and before the initiation of new DNA synthesis.

QT interval prolongation as predictor of sudden death in patients with myocardial infarction.

Abstract: Fifty-five patients with recent myocardial infarction and 55 healthy controls, matched for age, sex, race, height, weight, education and job, had an electrocardiogram taken every two months for seven years. Twenty-eight patients and one control had a sudden cardiac death. The QTc (mean of all values recorded) was found prolonged in one control (2%), five of 27 surviving patients (18%) and in 16 of 28 patients who had sudden death (57%). The difference between surviving and sudden death patients is significant (P less than 0.01). It is interesting that the only control with a long QT was the one when died suddenly of myocardial infarction. Among patients with previous myocardial infarction a prolonged QTc constitutes a 2.16 times greater risk for sudden death. We conclude that a constant prolongation of QTc in patients with myocardial infarction may help, with other risk factors, in defining a subgroup at higher risk for sudden death.

SUMO modification of Huntingtin and Huntington's disease pathology

Abstract: Huntington's disease (HD) is characterized by the accumulation of a pathogenic protein, Huntingtin (Htt), that contains an abnormal polyglutamine expansion. Here, we report that a pathogenic fragment of Htt (Httex1p) can be modified either by small ubiquitin-like modifier (SUMO)-1 or by ubiquitin on identical lysine residues. In cultured cells, SUMOylation stabilizes Httex1p, reduces its ability to form aggregates, and promotes its capacity to repress transcription. In a Drosophila model of HD, SUMOylation of Httex1p exacerbates neurodegeneration, whereas ubiquitination of Httex1p abrogates neurodegeneration. Lysine mutations that prevent both SUMOylation and ubiquitination of Httex1p reduce HD pathology, indicating that the contribution of SUMOylation to HD pathology extends beyond preventing Htt ubiquitination and degradation.