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- Svanborg, Catharina, et al.
(författare)
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The 'innate' host response protects and damages the infected urinary tract
- 2001
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Ingår i: Annals of Medicine. - 1365-2060. ; 33:9, s. 563-570
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Tidskriftsartikel (refereegranskat)abstract
- Symptoms of infection and tissue pathology are caused by the host response; not by the microbe per se. The same response is also critical for the defence and is needed to clear infection. It is therefore essential to understand how the host response is activated and to identify the critical effector mechanisms of the defence. We have studied these issues in the urinary tract infection (UTI) model. The symptoms of UTI and the host defence both rely on the so-called 'innate' immune system, making this one of the best characterized human disease models of 'innate immunity. We discuss the critical molecular events that determine whether the host response will be activated by P-fimbriated uropathogenic Escherichia coli as well as factors determining whether the patient develops acute pyelonephritis or asymptomatic bacteriuria. We will describe the glycoconjugate receptors used by the P-fimbriated bacteria adhering to host tissues, the recruitment of TLR4 co-receptors and the signalling pathways that allow progression to symptomatic disease, and discuss how these mechanisms are altered in asymptomatic carriers, presenting the possible genetic basis for unresponsiveness. We have shown that neutrophils are the critical effectors of the host defence and that neutrophil dysfunctions lead to acute pyelonephritis and renal scarring. Here we discuss the mechanisms of neutrophil-mediated, chemokine receptor (CXCR1)-dependent clearance, and the defect in interleukin-8 receptor homolog knock-out (IL-8Rh KO) mice and describe the data linking low CXCR1 expression to recurrent pyelonephritis in man, as well as the information on the genetic basis for low CXCR1 expression in affected patients. Finally, the mechanisms of renal scarring in IL8Rh KO mice will be discussed in relation to human disease. Our studies hold the promise to provide a molecular and genetic explanation for disease susceptibility in some patients with UTI and to offer more precise tools for the diagnosis and therapy of these infections.
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- Hang, L, et al.
(författare)
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Cytokine repertoire of epithelial cells lining the human urinary tract
- 1998
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Ingår i: The Journal of urology. - 0022-5347. ; 159:6, s. 92-2185
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To examine the cytokine profile of epithelial cells lining the human urinary tract with the aim of differentiating between the constitutive and disease-related cytokine production in these tissues.MATERIALS AND METHODS: Sections from the renal pelvis, ureter, bladder or urethra were obtained from 22 patients undergoing urinary tract surgery and were stained with monoclonal antibodies to interleukin(IL)-1beta, IL-4, IL-6, IL-8, interferon gamma (IFNgamma) and transforming growth factor beta (TGFbeta). Sections were classified according to the presence or absence of disease in the tissue.RESULTS: Epithelial cells lining the renal pelvis, ureter, bladder or urethra all stained for IL-8 and TGFbeta (100%) in disease-free tissues and sections with cancer or interstitial cystitis (IC). In contrast, staining for IL-1beta, IL-4, IL-6 and IFNgamma varied with the disease state of the patient. Epithelial IL-1beta staining was absent (0%) in sections from healthy bladder, but positive in tissues with IC or cancer-associated pathology (50 to 100%). IL-6 staining was detected in the epithelial layer of several patients with IC or cancer related pathology, but only in cells with non-epithelial morphology and not in disease-free tissues. IFNgamma and IL-4 staining were only observed in patients with IC and only in cells with non-epithelial morphology.CONCLUSIONS: The results show that epithelial cells from all parts of the urinary tract constitutively produce IL-8 and TGFbeta and suggest that the production of other cytokines varies with the disease of the patient. Constitutive cytokine production provides the basis for a rapid host response, in the defense against mucosal attack by microbes or toxic agents.
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- Köves, Béla, et al.
(författare)
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Benefits and Harms of Treatment of Asymptomatic Bacteriuria : A Systematic Review and Meta-analysis by the European Association of Urology Urological Infection Guidelines Panel
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838.
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Tidskriftsartikel (refereegranskat)abstract
- People with asymptomatic bacteriuria (ABU) are often unnecessarily treated with antibiotics risking adverse effects and antimicrobial resistance. We performed a systematic review to determine any benefits and harms of treating ABU in particular patient groups. Relevant databases were searched and eligible trials were assessed for risk-of-bias and Grading of Recommendations, Assessment, Development and Education quality. Where possible, a meta-analysis of extracted data was performed or a narrative synthesis of the evidence was presented. After screening 3626 articles, 50 studies involving 7088 patients were included. Overall, quality of evidence ranged from very low to low. There was no evidence of benefit for patients with no risk factors, patients with diabetes mellitus, postmenopausal women, elderly institutionalised patients, patients with renal transplants, or patients prior to joint replacement, and treatment was harmful for patients with recurrent urinary tract infection (UTI). Treatment of ABU resulted in a lower risk of postoperative UTI after transurethral resection surgery. In pregnant women, we found evidence that treatment of ABU decreased risk of symptomatic UTI, low birthweight, and preterm delivery. ABU should be treated prior to transurethral resection surgery. In addition, current evidence also suggests that ABU treatment is required in pregnant women, although the results of a recent trial have challenged this view. Patient summary: We reviewed available scientific studies to see if people with bacteria in their urine but without symptoms of urinary tract infection should be treated with antibiotics to eliminate bacteria. For most people, treatment was not beneficial and may be harmful. Antibiotic treatment did appear to benefit women in pregnancy and those about to undergo urological surgery. Treatment of asymptomatic bacteriuria is not beneficial in most patient groups. It should be treated only prior to endourological procedures and pregnancy. However, in the latter group, more up-to-date studies are needed to confirm benefit in modern healthcare settings.
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- Svanborg, Catharina, et al.
(författare)
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Adhesion, signal transduction and mucosal inflammation
- 2002
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Ingår i: Bacterial Adhesion to Host Tissues. - Cambridge : Cambridge University Press. - 9780521801072 - 0521801079 ; , s. 223-246
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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- Wullt, Bernhard, et al.
(författare)
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Neural motion planning in dynamic environments
- 2023
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Ingår i: IFAC-PapersOnLine. - : Elsevier. ; , s. 10126-10131
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Konferensbidrag (refereegranskat)abstract
- Motion planning is a mature field within robotics with many successful solutions. Despite this, current state-of-the-art planners are still computationally heavy. To address this, recent work have employed ideas from machine learning, which have drastically reduced the computational cost once a planner has been trained. It is mainly static environments that have been studied in this way. We continue along the same research direction but expand the problem to include dynamic environments, hence increasing the difficulty of the problem. Analogously to previous work, we use imitation learning, where a planning policy is learnt from an expert planner in a supervised manner. Our main contribution is a planner mimicking an expert that considers the future movement of all the obstacles in the environment, which is key in order to learn a successful policy in dynamic environments. We illustrate this by evaluating our approach in a dynamic environment and by comparing our planner with a conventional planner that re-plans at every iteration, which is a common approach in dynamic motion planning. We observe that our approach yields a higher success rate, while also taking less time and accumulating less distance to reach the goal.
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