| 1. |
|
|
| 2. |
- Huang, Jiaqi, et al.
(författare)
-
Helicobacter pylori infection, chronic corpus atrophic gastritis and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort : A nested case-control study
- 2017
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 140:8, s. 1727-1735
-
Tidskriftsartikel (refereegranskat)abstract
- The association between H. pylori infection and pancreatic cancer risk remains controversial. We conducted a nested case-control study with 448 pancreatic cancer cases and their individually matched control subjects, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, to determine whether there was an altered pancreatic cancer risk associated with H. pylori infection and chronic corpus atrophic gastritis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for matching factors and other potential confounders. Our results showed that pancreatic cancer risk was neither associated with H. pylori seropositivity (OR = 0.96; 95% CI: 0.70, 1.31) nor CagA seropositivity (OR = 1.07; 95% CI: 0.77, 1.48). We also did not find any excess risk among individuals seropositive for H. pylori but seronegative for CagA, compared with the group seronegative for both antibodies (OR = 0.94; 95% CI: 0.63, 1.38). However, we found that chronic corpus atrophic gastritis was non-significantly associated with an increased pancreatic cancer risk (OR = 1.35; 95% CI: 0.77, 2.37), and although based on small numbers, the excess risk was particularly marked among individuals seronegative for both H. pylori and CagA (OR = 5.66; 95% CI: 1.59, 20.19, p value for interaction < 0.01). Our findings provided evidence supporting the null association between H. pylori infection and pancreatic cancer risk in western European populations. However, the suggested association between chronic corpus atrophic gastritis and pancreatic cancer risk warrants independent verification in future studies, and, if confirmed, further studies on the underlying mechanisms.
|
|
| 3. |
- Ndegwa, Nelson, et al.
(författare)
-
Gastric Microbiota in a Low-Helicobacter pylori Prevalence General Population and Their Associations With Gastric Lesions
- 2020
-
Ingår i: Clinical and Translational Gastroenterology. - : LIPPINCOTT WILLIAMS & WILKINS. - 2155-384X. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION:Non-Helicobacter pylori microbiota might account for some cases with unexplained chronic gastritis that may in a minority eventually progress to gastric cancer through the Correa cascade. We characterized gastric microbiota by describing the normal stomach, compared it with early precancerous lesions and other disease states, and assessed whether H. pylori status affects bacterial diversity.METHODS:In a population-based study of those with and without gastrointestinal symptoms, cytology brush samples were collected during endoscopy from 316 individuals. Mucosal status was classified as normal mucosa (171), nonatrophic H. pylori gastritis (33), atrophic gastritis (12), or antral chemical gastritis (61). The 16S rRNA gene sequencing and analysis were performed to characterize the microbiota.RESULTS:Microbiota in atrophic gastritis and nonatrophic H. pylori gastritis stomachs were dysbiotic and differed from those in the normal stomach (P = 0.001). The normal stomach had the highest microbial diversity, followed by antral chemical gastritis. The atrophic gastritis and chronic H. pylori gastritis groups had the lowest diversity, a difference that was statistically significant (P = 0.01). Besides H. pylori, non-H. pylori bacteria accounted for group differences. Microbial network analysis showed that the normal group network was most highly connected, whereas the H. pylori gastritis group had the lowest connection. We found an increasing positive co-occurrence of oral bacteria in the stomach because samples deviated from the normal network, some of which were pathogens. The H. pylori-negative group had the highest microbial diversity (Shannon index) compared with the H. pylori-positive group (P = 0.001).DISCUSSION:In this low-H. pylori prevalence general population, the gastric mucosal microbiota of the normal stomach differed significantly from those with nonatrophic or atrophic gastritis. There was an increasing abundance of pathogenic bacteria from the normal state to early precancerous states.
|
|
| 4. |
- Rubin, Jenny, et al.
(författare)
-
The coding ECP 434(G>C) gene polymorphism determines the cytotoxicity of ECP but has minor effects on fibroblast-mediated gel contraction and no effect on RNase activity
- 2009
-
Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 183:1, s. 445-451
-
Tidskriftsartikel (refereegranskat)abstract
- Eosinophil cationic protein (ECP) is a secretory protein of the eosinophil granulocyte, a cell involved in innate immunity. Functional studies have implicated ECP in numerous processes, such as tissue remodeling in allergic inflammation and cytotoxicity toward a variety of pathogens. Recent genetic studies have suggested that the ECP 434(G>C) polymorphism resulting in an arg97thr substitution would alter the function of ECP in vivo. Functional (in vitro) studies of ECP up until now have either been conducted with native preparations containing an unknown mixture of the ECP(97arg) and ECP(97thr) variants, or with recombinant proteins. Therefore, we have now for the first time extracted the native ECP(97arg) and ECP(97thr) variants from healthy blood donors and tested them functionally in vitro. Our results show that the arg97thr shift dramatically alters the cytotoxic capacity of ECP in vitro; the tested ECP(97arg) variants were cytotoxic toward the small-cell lung cancer cell line NCI-H69, whereas ECP(97thr) was noncytotoxic. RNase activity was unaffected by the arg97thr substitution. Both ECP(97arg) and ECP(97thr) stimulated fibroblast-mediated collagen gel contraction, an experimental model, which depicts wound healing, in a dose-dependent manner. In conclusion, our results demonstrate that the ECP 434(G>C) gene polymorphism affects the functional properties of native ECP, but also that there is a dissociation between different biological activities; the arg97thr substitution impairs the cytotoxic potential of ECP but less the gel contraction and not at all the RNase activity.
|
|
| 5. |
- Sun, Jiangwei, et al.
(författare)
-
Antibiotics Use and Risk of Amyotrophic Lateral Sclerosis in Sweden
- 2019
-
Ingår i: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 26:11, s. 1355-1361
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Previous animal studies have suggested disrupted intestinal microbiome in amyotrophic lateral sclerosis (ALS). Due to the known effect of antibiotics on gut microflora, the potential role of antibiotics use on the risk of ALS deserves an investigation.METHODS: A nested case-control study was conducted using several Swedish national registers. We included 2,484 ALS patients diagnosed between July 1, 2006 and December 31, 2013 as cases and randomly selected five controls per case who were individually matched to the case by sex, birth year, and area of residence from the general Swedish population. Information on antibiotics prescriptions before ALS diagnosis was extracted from the Prescribed Drug Register for both cases and controls. Conditional logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).RESULTS: After accounting for potential diagnostic delay in ALS by excluding all prescriptions within one year before diagnosis, any antibiotics use was associated with a higher risk of ALS. The ORs (95% CIs) were 1.06 (0.94-1.19), 1.13 (1.00-1.28), and 1.18 (1.03-1.35) when comparing one, 2-3, and ≥4 prescriptions to no prescription (P for trend = 0.0069). Similar results were noted for antibiotics used for respiratory infections and urinary tract as well as skin and soft tissue infections. Among different individual antibiotics, the risk of ALS was especially increased in relation to more than two prescriptions of beta-lactamase sensitive penicillin (OR=1.28; 95% CI 1.10-1.50).CONCLUSIONS: Use of antibiotics, especially repeated, might be associated with a higher subsequent risk of ALS.
|
|
| 6. |
- Sun, Jiangwei, et al.
(författare)
-
Hospital-treated infections in early- and mid-life and risk of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis : A nationwide nested case-control study in Sweden
- 2022
-
Ingår i: PLoS Medicine. - : Public Library of Science. - 1549-1277 .- 1549-1676. ; 19:9
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Experimental observations have suggested a role of infection in the etiology of neurodegenerative disease. In human studies, however, it is difficult to disentangle whether infection is a risk factor or rather a comorbidity or secondary event of neurodegenerative disease. To this end, we examined the risk of 3 most common neurodegenerative diseases in relation to previous inpatient or outpatient episodes of hospital-treated infections.Methods and findings: We performed a nested case-control study based on several national registers in Sweden. Cases were individuals newly diagnosed with Alzheimer's disease (AD), Parkinson's disease (PD), or amyotrophic lateral sclerosis (ALS) during 1970 to 2016 in Sweden, identified from the National Patient Register. For each case, 5 controls individually matched to the case on sex and year of birth were randomly selected from the general population. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) with adjustment for potential confounders, including sex, year of birth, area of residence, educational attainment, family history of neurodegenerative disease, and Charlson comorbidity index. Infections experienced within 5 years before diagnosis of neurodegenerative disease were excluded to reduce the influence of surveillance bias and reverse causation. The analysis included 291,941 AD cases (median age at diagnosis: 76.2 years; male: 46.6%), 103,919 PD cases (74.3; 55.1%), and 10,161 ALS cases (69.3; 56.8%). A hospital-treated infection 5 or more years earlier was associated with an increased risk of AD (OR = 1.16, 95% CI: 1.15 to 1.18, P < 0.001) and PD (OR = 1.04, 95% CI: 1.02 to 1.06, P < 0.001). Similar results were observed for bacterial, viral, and other infections and among different sites of infection including gastrointestinal and genitourinary infections. Multiple infections before age 40 conveyed the greatest risk of AD (OR = 2.62, 95% CI: 2.52 to 2.72, P < 0.001) and PD (OR = 1.41, 95% CI: 1.29 to 1.53, P < 0.001). The associations were primarily due to AD and PD diagnosed before 60 years (OR = 1.93, 95% CI: 1.89 to 1.98 for AD, P < 0.001; OR = 1.29, 95% CI: 1.22 to 1.36 for PD, P < 0.001), whereas no association was found for those diagnosed at 60 years or older (OR = 1.00, 95% CI: 0.98 to 1.01 for AD, P = 0.508; OR = 1.01, 95% CI: 0.99 to 1.03 for PD, P = 0.382). No association was observed for ALS (OR = 0.97, 95% CI: 0.92 to 1.03, P = 0.384), regardless of age at diagnosis. Excluding infections experienced within 10 years before diagnosis of neurodegenerative disease confirmed these findings. Study limitations include the potential misclassification of hospital-treated infections and neurodegenerative diseases due to incomplete coverage of the National Patient Register, as well as the residual confounding from unmeasured risk or protective factors for neurodegenerative diseases.Conclusions: Hospital-treated infections, especially in early- and mid-life, were associated with an increased risk of AD and PD, primarily among AD and PD cases diagnosed before 60 years. These findings suggest that infectious events may be a trigger or amplifier of a preexisting disease process, leading to clinical onset of neurodegenerative disease at a relatively early age. However, due to the observational nature of the study, these results do not formally prove a causal link.
|
|
| 7. |
- Zagai, Ulrika, et al.
(författare)
-
Eosinophil cationic protein stimulates migration of human lung fibroblasts in vitro
- 2009
-
Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 69:4, s. 381-386
-
Tidskriftsartikel (refereegranskat)abstract
- Asthma is characterized by eosinophilic inflammation and remodelling of the airways. Eosinophil cationic protein (ECP) is a protein released by activated eosinophils and the hypothesis that ECP contributes to the development of structural changes in the airways of asthmatics has been posed. Fibroblast recruitment is an important step in the remodelling process, and we therefore put the question whether ECP stimulates migration of human lung fibroblasts. Human peripheral eosinophils isolated from buffycoats from healthy individuals were cultured and conditioned media (CM) were collected. Native ECP was extracted from human peripheral eosinophils by gel filtration, ion-exchange and chelating chromatography. The ability of eosinophil CM and ECP to stimulate fibroblast migration was determined using the 48-well Boyden chamber. ECP concentrations in CM were assayed by ECP-CAP-FEIA. Both CM and ECP significantly stimulated fibroblast migration (48.4+/-cells/field versus 33+/-2 and 36+/-6 versus 25+/-4; P<0.001 and 0.05 respectively) in a time- and concentration-dependent manner. Adding neutralizing ECP antibodies attenuated fibroblast migration induced by both ECP as well as CM. ECP stimulates migration of human lung fibroblasts, suggesting a potential mechanism for eosinophils in the fibrotic response. This may be an important mechanism by which ECP promotes remodelling of extracellular matrix leading to airway fibrosis in asthmatics.
|
|
| 8. |
- Zagai, Ulrika, et al.
(författare)
-
Eosinophil Cationic Protein Stimulates TGF-β1 Release by Human Lung Fibroblasts In Vitro
- 2007
-
Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 30:5, s. 153-160
-
Tidskriftsartikel (refereegranskat)abstract
- Eosinophilic inflammation and airway remodeling are features of asthma. Eosinophil cationic protein ( ECP) is released by activated eosinophils and transforming growth factor ( TGF)beta(1) has major functions in the fibrotic process. We therefore hypothesized that ECP stimulates TGF-beta(1) release by human lung fibroblasts. Fibroblasts in monolayer displayed a constitutive release of TGF-beta(1), which increased in presence of ECP ( 436 +/- 60 vs. 365 +/- 48 pg/ ml at 48 h; P< 0.01). mRNA expression of TGF-beta(1) was almost twofold in ECP- stimulated fibroblasts. ECP in threedimensional cultures stimulated both TGF-beta(1) release ( 180 +/- 61 vs. 137 +/- 54 pg/ ml; P< 0.01) and fibroblast- mediated collagen gel contraction ( 28 vs. 39% of initial gel area at 48 h; P< 0.001). ECP stimulates TGF-beta(1) release by human lung fibroblasts, suggesting a potential mechanism for eosinophils in the fibrotic response. This may be an important mechanism by which ECP promotes remodeling of extra cellular matrix leading to airway fibrosis in asthmatics.
|
|
| 9. |
- Zagai, Ulrika
(författare)
-
Platelets and eosinophils in lung tissue remodelling
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tissue injury and inflammation followed by effective repair restores normal function, but defective repair with associated tissue remodelling and fibrosis can lead to loss of organ function. Thus, interactions between inflammatory and mesenchymal cells in connection with the remodelling processes are of considerable importance with regards to the development of pulmonary disorders, since this interplay determines the outcome of the disease. At present, no clinical treatment for fibrosis is available and it is of considerable importance to improve our knowledge concerning the mechanisms that lead to tissue remodelling and fibrosis in order to develop effective therapeutic strategies. The present thesis was designed to explore the impact of two important inflammatory cells, platelets and eosinophils, on remodelling of lung tissue employing systems. Data are based on experimental models such as fibroblast-mediated contraction of collagen gels, which reflects the contractile process typical of tissue remodelling. In this model human lung fibroblasts are cultured in an artificial lung tissue consisting of type I collagen. The advantages of vivo and, furthermore, demonstrate more in vivo-like functional properties. To monitor fibroblast recruitment, which is also an important step in the remodelling process, we employed Boyden chambers with type I collagen coated filters. Platelets and eosinophils were cultured together with fibroblasts in collagen gels to explore the influence of these cells on gel contraction. Both platelets and lysate thereof stimulated fibroblastmediated contraction of collagen gels and both PDGF and TGF-â contributed partially to this effect. Furthermore, both peripheral blood eosinophils and eosinophil-like differentiated HL-60 clone 15 cells stimulated the fibroblast-mediated collagen gel contraction. ECP was one of the proteins produced by eosinophils involved in this interaction between eosinophils and lung fibroblasts. Moreover, ECP stimulated the release of TGF-â by both monolayer and threedimensional cultures of lung fibroblasts. ECP also enhanced the level of TGF-â mRNA in these lung fibroblasts. Both media from cultures of peripheral blood eosinophils and ECP (native and recombinant) alone stimulated the migration of lung fibroblasts, effects that were attenuated by neutralising antibodies directed towards ECP. The present thesis highlights the ways in which platelets and eosinophils can influence fibroblasts and the extracellular matrix in vitro. Based on our findings, we propose that platelets and eosinophils participate in tissue remodelling in vivo. The results documented here offer some possible explanations and mechanisms with regards to how these inflammatory cells may contribute to defective tissue repair, fibrosis and impaired pulmonary function.
|
|
| 10. |
- Zagai, Ulrika, et al.
(författare)
-
The effect of eosinophils on collagen gel contraction and implications for tissue remodelling
- 2004
-
Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 135:3, s. 427-433
-
Tidskriftsartikel (refereegranskat)abstract
- Asthma is characterized by an eosinophilic inflammation and a subepithelial fibrosis in the airways. Eosinophils contain several cytotoxic substances, such as eosinophil cationic protein (ECP), which can promote inflammation and cause tissue damage. This has generated the hypothesis that eosinophils may drive remodelling of extracellular matrix (ECM). To investigate the role of eosinophils we used an in vitro model for remodelling, the three-dimensional collagen gel contraction assay. Two sources of eosinophils were used in this study, isolated human peripheral eosinophils (purity > 95%) and stimulated [interleukin (IL)-5, IL-3 and granulocyte macrophage-colony stimulating factor (GM-CSF)] HL-60 clone 15 cells. Human eosinophils or HL-60 cells were cast together with human lung fibroblasts (HFL1) in type I collagen gels. Both types of eosinophils augmented fibroblast-mediated collagen gel contraction in a time and concentration-dependent manner. At 48 h, the gel area in HFL1/eosinophil co-culture was 46.5% +/- 0.5 (mean +/- s.e.m.) of initial area and in HFL1 culture 52.3% +/- 0.1 (P < 0.001). Respective figures for HFL1/stimulated HL-60 co-culture and HFL1 culture only were 44.1% +/- 0.5 and 52.4% +/- 0.4 (P < 0.001). The release of ECP was increased when fibroblasts were cultured with eosinophils compared to eosinophils cultured alone. In addition, native ECP added to fibroblast gel cultures also augmented contraction. Our results suggest that eosinophils may interact with mesenchymal cells, promoting remodelling of ECM and that ECP constitutes one potential eosinophil-derived mediator driving this process. We conclude that this may be one important mechanism by which eosinophil-ECM interactions will lead to airway tissue remodelling in asthma.
|
|
