University of Münster

About: University of Münster is a education organization based out in Münster, Germany. It is known for research contribution in the topics: Population & Catalysis. The organization has 35609 authors who have published 69059 publications receiving 2278534 citations. The organization is also known as: University of Munster & University of Muenster.

Sex and virulence in Escherichia coli: an evolutionary perspective

Abstract: Summary Pathogenic Escherichia coli cause over 160 million cases of dysentery and one million deaths per year, whereas non-pathogenic E. coli constitute part of the normal intestinal flora of healthy mammals and birds. The evolutionary pathways underlying this dichotomy in bacterial lifestyle were investigated by multilocus sequence typing of a global collection of isolates. Specific pathogen types (enterohaemorrhagic E. coli , enteropathogenic E. coli , enteroinvasive E. coli , K1 and Shigella ) have arisen independently and repeat- edly in several lineages, whereas other lineages con- tain only few pathogens. Rates of evolution have accelerated in pathogenic lineages, culminating in highly virulent organisms whose genomic contents are altered frequently by increased rates of homolo- gous recombination; thus, the evolution of virulence is linked to bacterial sex. This long-term pattern of evolution was observed in genes distributed through- out the genome, and thereby is the likely result of episodic selection for strains that can escape the host immune response.

Nasal Carriage as a Source of Staphylococcus aureus Bacteremia

Abstract: Background The consequences of infection with Staphylococcus aureus can be severe, so strategies for prevention are important. We examined S. aureus isolates from blood and from nasal specimens to determine whether the organisms in the bloodstream originated from the patient's own flora. Methods In a multicenter study, swabs for culture were obtained from the anterior nares of 219 patients with S. aureus bacteremia. A total of 723 isolates were collected and genotyped. In a second study, 1640 S. aureus isolates from nasal swabs from 1278 patients were collected over a period of five years and then compared with isolates from the blood of patients who subsequently had S. aureus bacteremia. Results In the multicenter study of S. aureus bacteremia, the blood isolates were identical to those from the anterior nares in 180 of 219 patients (82.2 percent). In the second study, 14 of 1278 patients who had nasal colonization with S. aureus subsequently had S. aureus bacteremia. In 12 of these 14 patients (86 perce...

Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma.

Abstract: The time to progression among patients receiving bortezomib plus melphalan– prednisone (bortezomib group) was 24.0 months, as compared with 16.6 months among those receiving melphalan–prednisone alone (control group) (hazard ratio for the bortezomib group, 0.48; P<0.001). The proportions of patients with a partial response or better were 71% in the bortezomib group and 35% in the control group; complete-response rates were 30% and 4%, respectively (P<0.001). The median duration of the response was 19.9 months in the bortezomib group and 13.1 months in the control group. The hazard ratio for overall survival was 0.61 for the bortezomib group (P = 0.008). Adverse events were consistent with established profiles of toxic events associated with bortezomib and melphalan–prednisone. Grade 3 events occurred in a higher proportion of patients in the bortezomib group than in the control group (53% vs. 44%, P = 0.02), but there were no significant differences in grade 4 events (28% and 27%, respectively) or treatment-related deaths (1% and 2%). Conclusions Bortezomib plus melphalan–prednisone was superior to melphalan–prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy. (ClinicalTrials.gov number, NCT00111319.)

Genetic basis and molecular mechanism for idiopathic ventricular fibrillation

Abstract: Ventricular fibrillation causes more than 300,000 sudden deaths each year in the USA alone. In approximately 5-12% of these cases, there are no demonstrable cardiac or non-cardiac causes to account for the episode, which is therefore classified as idiopathic ventricular fibrillation (IVF). A distinct group of IVF patients has been found to present with a characteristic electrocardiographic pattern. Because of the small size of most pedigrees and the high incidence of sudden death, however, molecular genetic studies of IVF have not yet been done. Because IVF causes cardiac rhythm disturbance, we investigated whether malfunction of ion channels could cause the disorder by studying mutations in the cardiac sodium channel gene SCN5A. We have now identified a missense mutation, a splice-donor mutation, and a frameshift mutation in the coding region of SCN5A in three IVF families. We show that sodium channels with the missense mutation recover from inactivation more rapidly than normal and that the frameshift mutation causes the sodium channel to be non-functional. Our results indicate that mutations in cardiac ion-channel genes contribute to the risk of developing IVF.

FGF23 induces left ventricular hypertrophy

Abstract: Chronic kidney disease (CKD) is a public health epidemic that increases risk of death due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiovascular disease in individuals with CKD. Elevated levels of FGF23 have been linked to greater risks of LVH and mortality in patients with CKD, but whether these risks represent causal effects of FGF23 is unknown. Here, we report that elevated FGF23 levels are independently associated with LVH in a large, racially diverse CKD cohort. FGF23 caused pathological hypertrophy of isolated rat cardiomyocytes via FGF receptor–dependent activation of the calcineurin-NFAT signaling pathway, but this effect was independent of klotho, the coreceptor for FGF23 in the kidney and parathyroid glands. Intramyocardial or intravenous injection of FGF23 in wild-type mice resulted in LVH, and klotho-deficient mice demonstrated elevated FGF23 levels and LVH. In an established animal model of CKD, treatment with an FGF–receptor blocker attenuated LVH, although no change in blood pressure was observed. These results unveil a klotho-independent, causal role for FGF23 in the pathogenesis of LVH and suggest that chronically elevated FGF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD.