| 1. |
- Ahlgren, Kerstin M., et al.
(författare)
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Increased IL-17A secretion in response to Candida albicans in autoimmune polyendocrine syndrome type 1 and its animal model
- 2011
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 41:1, s. 235-245
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal failure are hallmarks of the disease. The critical mechanisms causing chronic mucocutaneous candidiasis in APS-1 patients have not been identified although autoantibodies to cytokines are implicated in the pathogenesis. To investigate whether the Th reactivity to Candida albicans (C. albicans) and other stimuli was altered, we isolated PBMC from APS-1 patients and matched healthy controls. The Th17 pathway was upregulated in response to C. albicans in APS-1 patients, whereas the IL-22 secretion was reduced. Autoantibodies against IL-22, IL-17A and IL-17F were detected in sera from APS-1 patients by immunoprecipitation. In addition, Aire-deficient (Aire(0/0) ) mice were much more susceptible than Aire(+/+) mice to mucosal candidiasis and C. albicans-induced Th17- and Th1-cell responses were increased in Aire(0/0) mice. Thus an excessive IL-17A reactivity towards C. albicans was observed in APS-1 patients and Aire(0/0) mice.
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| 2. |
- Ardesjö, Brita, et al.
(författare)
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Identification of a novel staining pattern of bile duct epithelial cells in primary sclerosing cholangitis
- 2010
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998 .- 1536-4844. ; 16:2, s. 305-311
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Primary sclerosing cholangitis (PSC) is an inflammatory disease of the bile ducts with an unknown etiology. A number of autoantigens have been proposed, but an early diagnostic marker is still lacking. Our aim was to identify such an autoantigen. METHODS: Immunostaining was performed on normal human bile duct with sera from patients with PSC and controls. To identify an autoantigen a cDNA library from normal human choledochus was constructed and immunoscreened with patient sera. Using in vitro transcription and translation and immunoprecipitation we examined the immunoreactivity against PDZ domain containing 1 (PDZK1) in 35 patients with PSC, 198 control patients, and 94 healthy controls. RESULTS: We observed a previously unpublished staining pattern in which cytoplasmatic granules and apical cell membranes of biliary epithelial cells were stained by PSC sera. Strong immunoreactivity to these structures was obtained with 12 out of 35 PSC sera (34%) but not with sera from healthy controls. By screening the cDNA library we identified PDZK1 as a candidate antigen. Immunoreactivity against PDZK1 was detected in 9% of PSC patients, 2% of inflammatory bowel disease (IBD) patients, 8% of autoimmune pancreatitis patients, 18% of Grave's disease patients, and 1% of healthy controls. CONCLUSIONS: Previously unpublished, specific, and strong autoantibodies against epithelial cells of the bile duct in PSC sera were identified. Furthermore, PDZK1 is suggested as a potential new autoantigen.
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| 3. |
- Ardesjö Lundgren, Brita, et al.
(författare)
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Identification of complement C3 as an autoantigen in inflammatory bowel disease.
- 2010
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Ingår i: European journal of gastroenterology & hepatology. - 1473-5687 .- 0954-691X. ; 22:4, s. 429-436
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Autoantibodies against goblet cells in the gastrointestinal mucosa have been described in patients with inflammatory bowel disease (IBD) but a corresponding autoantigen has not yet been identified. The aim of this study was to identify such an antigen. METHODS: First, 10 candidate autoantigens were discarded based on double stainings of appendiceal sections and a mucin-producing cell line (HT29-mtx). Second, an appendiceal cDNA library was immunoscreened with IBD sera. RESULTS: Three out of 48 positive clones were identified as complement C3. Using immunoprecipitation of in vitro transcribed and translated C3, seven of 17 primary sclerosing cholangitis patient sera, 15 of 65 IBD sera, and none out of 54 sera from healthy blood donors showed C3 immunoreactivity. The results were confirmed using western blot and an enzyme-linked immunosorbent assay with alternative sources of C3 protein. CONCLUSION: In conclusion, we have identified complement C3 as a potential autoantigen in IBD and primary sclerosing cholangitis.
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| 4. |
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| 5. |
- Fagerlind, Martin, 1980, et al.
(författare)
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Investigation of the interface between silicon nitride passivations and AlGaN/AlN/GaN heterostructures by C(V) characterization of metal-insulator-semiconductor-heterostructure capacitors
- 2010
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 108:1
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Tidskriftsartikel (refereegranskat)abstract
- Capacitance-voltage [C(V)] measurements of metal-insulator-semiconductor-heterostructure capacitors are used to investigate the interface between silicon nitride passivation and AlGaN/AlN/GaN heterostructure material. AlGaN/AlN/GaN samples having different silicon nitride passivating layers, deposited using three different deposition techniques, are evaluated. Different interface state distributions result in large differences in the C(V) characteristics. A method to extract fixed charge as well as traps from the C(V) characteristics is presented. Rough estimates of the emission time constants of the traps can be extracted by careful analysis of the C(V) characteristics. The fixed charge is positive for all samples, with a density varying between 1.3 x 10(12) and 7.1 x 10(12) cm(-2). For the traps, the peak density of interface states is varying between 16 x 10(12) and 31 x 10(12) cm(-2) eV(-1) for the three samples. It is concluded that, of the deposition methods investigated in this report, the low pressure chemical vapor deposited silicon nitride passivation shows the most promising results with regards to low densities of interface states. (C) 2010 American Institute of Physics. [doi:10.1063/1.3428442]
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| 6. |
- Hjelmgren, Hans, 1960, et al.
(författare)
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Transient Simulation of Microwave SiC MESFETs With Improved Trap Models
- 2010
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Ingår i: IEEE Transactions on Electron Devices. - 1557-9646 .- 0018-9383. ; 57:3, s. 729-732
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Tidskriftsartikel (refereegranskat)abstract
- Measured and simulated transient characteristics ofa SiC metal–semiconductor field-effect transistor are compared. Self-heating, gate tunneling, substrate, and surface traps are taken into account in the simulations. By explicitly filling surface traps at the vicinity of the gate during pinchoff, close correspondence between simulated and measured gate lags is achieved.
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| 7. |
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| 8. |
- Sangfelt, Per, et al.
(författare)
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Monitoring dominant strictures in primary sclerosing cholangitis with brush cytology and FDG-PET
- 2014
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 61:6, s. 1352-1357
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Despite a high risk of cholangiocellular adenocarcinoma (CCA) it is unclear how surveillance of patients with primary sclerosing cholangitis (PSC) should be performed. METHODS: We evaluated a follow-up algorithm of brush cytology and positron emission tomography/computed tomography with [(18)F] fluorodeoxyglucose ([(18)F]FDG-PET/CT), measured as maximum standardized uptake values, normalized to the liver background (SUVmax/liver) at 180 min, in PSC patients with dominant bile duct strictures. RESULTS: Brush cytology with high grade dysplasia (HGD) was detected in 12/70 patients (17%), yielding a diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 56%, 89%, 75%, and 88%, respectively. Preemptive liver transplantations due to repeated HGD before manifest CCA were performed in six patients. Receiver operating characteristic (ROC) analysis of [(18)F]FDG uptake showed that a SUVmax/liver quotient of 3.3 was able to discriminate between CCA and non-malignant disease with a sensitivity, specificity, PPV and NPV for CCA of 89%, 92%, 62%, 98%, respectively. A SUVmax/liver >3.3 detected CCA in 8/9 patients whereas a quotient <2.4 excluded CCA. Combining brush cytology and quantitative [(18)F]FDG-PET/CT yielded a sensitivity for HGD and/or CCA of 100% and a specificity of 88%. CONCLUSION: Early detection of HGD before manifest CCA is feasible with repeated brush cytology and may allow for preemptive liver transplantation. [(18)F]FDG-PET/CT has a high sensitivity for manifest CCA and a negative scan indicates a non-malignant state of the disease. Brush cytology and [(18)F]FDG-PET/CT are complementary in monitoring and managing PSC patients with dominant strictures.
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| 9. |
- Sangfelt, Per, et al.
(författare)
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Monitoring Dominant Strictures in Primary Sclerosing Cholangitis with Brush Cytology and FDG-PET
- 2014
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Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 61:6, s. 1352-1357
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Despite high risk of cholangiocellular adenocarcinoma (CCA) it is unclear how surveillance of patients with primary sclerosing cholangitis (PSC) should be performed.METHOD: We evaluated a follow-up algorithm of brush cytology and positron emission tomography/computed tomography with [18F]fluorodeoxyglucose ([18F]FDG-PET/CT), measured as the maximum standardized uptake values normalized to the liver background (SUVmax/liver) at 180 minutes, in PSC patients with dominant bile duct strictures.RESULTS: Brush cytology with high grade dysplasia (HGD) was detected in 12/70 patients (17%), yielding diagnostic sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 56%, 89%, 75% and 88%, respectively. Preemptive liver transplantations due to repeated HGD before manifest CCA were performed in six patients. Receiver operating characteristic (ROC) analysis of [18F]FDG uptake showed that a SUVmax/liver quotient of 3.3 was able to discriminate between CCA and non-malignant disease with a sensitivity, specificity, PPV and NPV for CCA of 89%, 92%, 62%, 98%, respectively. A SUVmax/liver >3.3 detected CCA in 8/9 patients whereas a quotient < 2.4 excluded CCA. Combining brush cytology and quantitative [18F]FDG-PET/CT yielded a sensitivity for HGD and/or CCA of 100% and a specificity of 88%.CONCLUSION: Early detection of HGD before manifest CCA is feasible with repeated brush cytology and may allow for preemptive liver transplantation. [18F]FDG-PET/CT has a high sensitivity for manifest CCA and a negative scan indicates a non-malignant state of the disease. Brush cytology and [18F]FDG-PET/CT are complementary in monitoring and managing PSC patients with dominant strictures.
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