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- Demirel, Isak, 1987-
(författare)
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Uropathogenic Esherichia coli, multidrug-resistance and induction of host defense mechanisms
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Uropathogenic Escherichia coli (UPEC) is the primary cause of urinary tract infection (UTI), which is one of the most common infections in humans. UPEC strains have acquired successful strategies to subvert the host defense and antibiotics to persist in the urinary tract. The main aim of this thesis was to investigate the host defense mechanisms during a UPEC infection in vitro.The results showed that SOCS3, a key regulator of the immune system, was increased in bladder epithelial cells in response to a UPEC infection. In addition, UPEC decreased the phosphorylation of the SOCS3 regulated transcription factor STAT3. Nitric oxide (NO), a host-derived antimicrobial factor was shown to increase the release of IL-6 from renal epithelial cells alone or in combination with UPEC. The induction of IL-6 was mediated by ERK1/2 and p38 MAPK signaling and NO was also shown to attenuate UPEC-induced IL-6 mRNA degradation. Furthermore, extended-spectrum beta-lactamase (ESBL)-producing UPEC isolates were shown to induce higher PMN migration and ROS-production, but lower cytokine secretion from renal epithelial cells than susceptible isolates. Ineffective ceftibuten treatment of ESBL isolates induced bacterial filamentation associated with an increased release of ATP and LPS, with a subsequent enhancement of the ESBL evoked host response.Taken together, the findings show that UPEC can induce SOCS3, a suppressor of host responses and that NO can regulate proinflammatory mediators. In addition, the data suggest that there are differences between ESBL- and non-ESBL-producing isolates ability to evoke a host response. Exposing resistant isolates to ineffective antibiotics was shown to alter the evoked host response.
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- Johansson, RK, et al.
(författare)
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Expression of nitric oxide synthase in bladder smooth muscle cells: Regulation by cytokines and L-arginine
- 2002
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Ingår i: Journal of Urology. - 1527-3792. ; 168:5, s. 2280-2285
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The expression and regulation of the different isoforms of nitric oxide synthase (NOS) in bladder smooth muscle cells are controversial and to our knowledge have not yet been studied systematically. Therefore, the expression and regulation of NOS were studied in rat bladder smooth muscle cells after stimulation with cytokines, lipopolysaccharide and L-arginine. Materials and Methods: Primary cell cultures were prepared from rat bladders. The expression of NOS mRNA was examined by reverse transcriptase-polymerase chain reaction and inducible NOS (iNOS) protein expression was studied by Western blot analysis and immunohistochemistry. Nitrite accumulation in the culture medium was determined by the Griess assay. The expression of iNOS was also studied immunohistochemically in whole bladder strips stimulated by cytokines. Results: NOS mRNA expression was not detected in unstimulated cells. Stimulating bladder smooth muscle cells with a cytokine mixture of interferon-gamma, tumor necrosis factor-alpha and interleukin-1beta induced iNOS mRNA and protein expression. The combination of interleukin-1beta plus tumor necrosis factor-alpha appeared to be crucial for iNOS induction in bladder smooth muscle cells. Exposing bladder smooth muscle cells to lipopolysaccharide did not induce iNOS. Adding L-arginine increased nitrite accumulation in cytokine mixture stimulated bladder smooth muscle cells, while iNOS positive cells were detected in the smooth muscle layer of cytokine mixture stimulated bladder strips. Conclusions: NOS was not detected in unstimulated bladder smooth muscle cells. However, bladder smooth muscle has the potential to express iNOS when exposed to cytokines known to be produced during urinary tract infection.
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- Kocjan, Boštjan J, et al.
(författare)
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Molecular methods for identification and characterization of novel papillomaviruses.
- 2015
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Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1469-0691 .- 1198-743X. ; 21:9, s. 808-816
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Forskningsöversikt (refereegranskat)abstract
- Papillomaviruses (PV) are a remarkably heterogeneous family of small DNA viruses that infect a wide variety of vertebrate species and are etiologically linked with the development of various neoplastic changes of the skin and mucosal epithelia. Based on nucleotide similarity, PVs are hierarchically classified into genera, species and types. Novel human PV (HPV) types are given a unique number only after the whole genome has been cloned and deposited with the International HPV Reference Center. As of March 09, 2015, 200 different HPV types, belonging to 49 species, had been recognized by the International HPV Reference Center. In addition, 131 animal PV types identified from 66 different animal species exist. Recent advances in molecular techniques have resulted in an explosive increase in the identification of novel HPV types and novel subgenomic HPV sequences in the last few years. Among PV genera, the Gamma-PV genus has been growing most rapidly in recent years with 80 completely sequenced HPV types, followed by Alpha- and Beta-PV genera that have 65 and 51 recognized HPV types, respectively. We reviewed in detail the contemporary molecular methods most often used for identification and characterization of novel PV types, including polymerase chain reaction, rolling circle amplification and next generation sequencing. Furthermore, we present a short overview of 12 and 10 novel HPV types recently identified in Sweden and Slovenia, respectively. Finally, an update on the International Human Papillomavirus Reference Center is provided.
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- Poljakovic, Mirjana, et al.
(författare)
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Escherichia coli-induced inducible nitric oxide synthase and cyclooxygenase expression in the mouse bladder and kidney
- 2001
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Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 59:3, s. 893-904
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The host response to urinary tract infection includes the production of different inflammatory mediators. We investigated the cellular localization and time course of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) expression in the mouse bladder and kidney after bacterial infection. METHODS: Experimental urinary tract infection in mice was established by intravesical inoculation of a clinical uropathogen Escherichia coli (E. coli) AD 110. Urine was collected at 6-, 12-, 24-, and 72-hours postinstillation, and the nitrite concentration was determined. The induction of iNOS and COX-2 was studied by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Nitrite levels in the urine had increased threefold at 6 and 12 hours postbacterial instillation. Bladders from mice instilled with AD 110, but not with phosphate-buffered saline, showed a large number of iNOS-- and COX-2--expressing inflammatory cells. The inflammatory cell activation peaked at 6 and 12 hours postinstillation and had vanished by 72 hours. iNOS expression was detected in some urothelial cells after 24 and 72 hours, but COX-2 expression was not detected. In the kidney, infection activated an iNOS and COX-2 response, as shown by immunoreactivity in inflammatory cells at all time points. A strong epithelial iNOS response was observed in the renal pelvis at 12, 24, and 72 hours postinstillation, but COX-2 was not detected. Enhanced tissue expression of iNOS and COX-2 after bacterial instillation was also demonstrated by RT-PCR. CONCLUSIONS: E. coli AD 110 induced expression of iNOS and COX-2 in the urinary tract. Inflammatory cells expressed both iNOS-and COX-2, but epithelial cells expressed only iNOS and with a later onset than in the inflammatory cells. This suggests that the epithelial iNOS response is not caused by direct bacterial activation, but more likely is by mediators involved in the inflammatory response.
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