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Ragnarsdóttir B Lutay N Grönberg-Hernandez J Köves B Svanborg C 《Nature reviews. Urology》2011,8(8):449-468
A functional and well-balanced immune response is required to resist most infections. Slight dysfunctions in innate immunity can turn the 'friendly' host defense into an unpleasant foe and give rise to disease. Beneficial and destructive forces of innate immunity have been discovered in the urinary tract and mechanisms by which they influence the severity of urinary tract infections (UTIs) have been elucidated. By modifying specific aspects of the innate immune response to UTI, genetic variation either exaggerates the severity of acute pyelonephritis to include urosepsis and renal scarring or protects against symptomatic disease by suppressing innate immune signaling, as in asymptomatic bacteriuria (ABU). Different genes are polymorphic in patients prone to acute pyelonephritis or ABU, respectively, and yet discussions of UTI susceptibility in clinical practice still focus mainly on social and behavioral factors or dysfunctional voiding. Is it not time for UTIs to enter the era of molecular medicine? Defining why certain individuals are protected from UTI while others have severe, recurrent infections has long been difficult, but progress is now being made, encouraging new approaches to risk assessment and therapy in this large and important patient group, as well as revealing promising facets of 'good' versus 'bad' inflammation. 相似文献
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Nataliya E. Yelina Lisa M. Smith Alexandra M. E. Jones Kanu Patel Krystyna A. Kelly David C. Baulcombe 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(31):13948-13953
RNA silencing in plants and some animals has a non–cell-autonomous effect due to an RNA signal that moves between cells or organs. To identify unique factors involved in this process, we analyzed a group of Arabidopsis mutants with defective spread of RNA silencing from a transgene expressed specifically in the phloem. These mutants accumulated reduced amounts of small interfering (si)RNA from the transgene locus and from endogenous loci TAS1, TAS2, and an inverted repeat locus IR71. The defect in TAS1 and TAS2 siRNA biogenesis is in the processing of a long siRNA precursor. We mapped the mutations to a gene encoding the Arabidopsis homolog of a protein, TEX1, which is involved in intracellular transport of RNA in animals. TEX1 is a component of the THO/TREX complex, and we show that the Arabidopsis TEX1 interacts with other predicted components of a THO/TREX complex. Correspondingly, we found at least two other components of the Arabidopsis THO core complex that are involved in RNA silencing. To reconcile the effect of these mutations on transgene and endogenous gene siRNA, we propose a mechanism in which THO/TREX processes or transports a long RNA molecule so that it can be a template for secondary siRNA production. 相似文献
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Nizar Souayah P.A. Michas-MartinAbu Nasar Nataliya KrivitskayaHussam A. Yacoub Hafiz KhanAdnan I. Qureshi 《Vaccine》2011,29(5):886-889
Using data from Vaccine Adverse Event Reporting System, we identified 69 reports of Guillain-Barré Syndrome (GBS) after Gardasil vaccination that occurred in the United States between 2006 and 2009. The onset of symptoms was within 6 weeks after vaccination in 70% of the patients in whom the date of vaccination was known. The estimated weekly reporting rate of post-Gardasil GBS within the first 6 weeks (6.6 per 10,000,000) was higher than that of the general population, and higher than post-Menactra and post-influenza vaccinations. Further prospective active surveillance for accurate ascertainment and identification of high-risk groups of GBS after Gardasil vaccination is warranted. 相似文献
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Svensson M Yadav M Holmqvist B Lutay N Svanborg C Godaly G 《Kidney international》2011,80(10):1064-1072
The CXCR1 receptor and chemokine CXCL8 (IL-8) support neutrophil-dependent clearance of uropathogenic Escherichia coli from the urinary tract. CXCR1 is reduced in children prone to pyelonephritis, and heterozygous hCXCR1 polymorphisms are more common in this patient group than in healthy individuals, strongly suggesting a disease association. Since murine CXCR2 (mCXCR2) is functionally similar to human CXCR1, we determined effects of gene heterozygosity on the susceptibility to urinary tract infection by infecting heterozygous (mCxcr2(+/-)) mice with uropathogenic Escherichia coli. Clearance of infection and tissue damage were assessed as a function of innate immunity in comparison to that in knockout (mCxcr2(-/-)) and wild-type (mCxcr2(+/+)) mice. Acute sepsis-associated mortality was increased and bacterial clearance drastically impaired in heterozygous compared to wild-type mice. Chemokine and neutrophil responses were delayed along with evidence of neutrophil retention and unresolved kidney inflammation 1 month after infection. This was accompanied by epithelial proliferation and subepithelial fibrosis. The heterozygous phenotype was intermediate, between knockout and wild-type mice, but specific immune cell infiltrates that accompany chronic infection in knockout mice were not found. Hence, the known heterozygous CXCR1 polymorphisms may predispose patients to acute pyelonephritis and urosepsis. 相似文献
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Primary sclerosing cholangitis (PSC) is a chronic fibroinflammatory syndrome involving the biliary tract, often accompanied by inflammatory bowel disease (IBD). This syndrome is a prototype disease linking chronic inflammation to carcinogenesis. Indeed, PSC is associated with an increased risk of cholangiocarcinoma (CCA), gallbladder cancer, hepatocellular carcinoma (HCC), and colorectal cancer. Herein, we review the risk for these malignancies in PSC and discuss rational cancer surveillance strategies for these patients. Where evidence is limited, we suggest a pragmatic approach. In this regard, we recommend interval screening for CCA with noninvasive imaging modalities and serum carbohydrate antigen 19-9 determinations annually. These imaging studies also serve to screen for gallbladder cancer and HCC. Screening for colorectal cancer is more firmly established in PSC patients with IBD and includes colonoscopy at the time of PSC diagnosis and, thereafter, at 1-2-year intervals. We also highlight areas where more information is required, such as management of biliary tract dysplasia and cancer chemoprevention in PSC. 相似文献
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