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- Arvonen, Miika, et al.
(författare)
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Gut microbiota-host interactions and juvenile idiopathic arthritis
- 2016
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Ingår i: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 14
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Forskningsöversikt (refereegranskat)abstract
- Background: Juvenile idiopathic arthritis is the most common form of chronic arthritis in children. There is mounting evidence that the microbiota may influence the disease. Main body: Recent observations in several systemic inflammatory diseases including JIA have indicated that abnormalities in the contents of the microbiota may be factors in disease pathogenesis, while other studies in turn have shown that environmental factors impacting the composition of the microbiota, such as delivery mode and early exposure to antibiotics, affect the risk of chronic inflammatory diseases including JIA. Microbial alterations may predispose to JIA through a variety of mechanisms, including impaired immunologic development, alterations in the balances of pro- versus anti-inflammatory bacteria, and low-grade mucosal inflammation. Additional confirmatory studies of microbiota aberrations and their risk factors are needed, as well as additional mechanistic studies linking these alterations to the disease itself. Conclusions: The microbiota may influence the risk of JIA and other systemic inflammatory conditions through a variety of mechanisms. Additional research is required to improve our understanding of the links between the microbiota and arthritis, and the treatment implications thereof.
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| 2. |
- Kauppila, Joonas H, et al.
(författare)
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Intratumoral lactate metabolism in Barrett’s esophagus and adenocarcinoma
- 2017
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Ingår i: Oncotarget. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1949-2553.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Monocarboxylate transporters (MCTs) are cell membrane proteins which transport pyruvate, lactate and ketone bodies across the plasma membrane. MCTs are activated in various cancers, but their expression in esophageal adenocarcinoma is not known. The present study was conducted to elucidate the expression of MCTs in esophageal adenocarcinoma and its precursor lesions. Results: Cytoplasmic MCT1, MCT4 and MTCO1 expression linearly increased from normal epithelium to Barrett's mucosa to dysplasia and cancer. Low cytoplasmic MCT1 expression associated with high T-class (P < 0.01), positive lymph node metastases (P < 0.05), positive distant metastases (P < 0.01) and high tumor stage (P < 0.01). High cytoplasmic MCT4 expression correlated significantly with positive distant metastases (P < 0.05). Both low MCT1 and high MCT4 histoscore predicted survival in univariate analysis (P < 0.01). MCT4 histoscore predicted survival in multivariate analysis (P = 0.043; HR 1.8 95%CI 1.0–3.1). MTCO1 expression was not correlated to clinicopathological variables or survival. Materials and Methods: MCT1, MCT4 and mitochondrial cytochrome c oxidase (MTCO1) expression were determined with immunohistochemistry in esophageal specimens from 129 patients with columnar dysplasia or adenocarcinoma. Specimens including normal esophagus (n = 88), gastric (n = 67) or intestinal metaplasia (n = 51), low-grade (n = 42), high-grade dysplasia (n = 37) and esophageal adenocarcinoma (n = 99) were evaluated. Conclusions: Major increase in markers of tumor metabolism occurs during carcinogenesis and progression of esophageal adenocarcinoma. MCT1 and MCT4 are prognostic factors in esophageal adenocarcinoma.
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| 3. |
- Kauppila, Joonas H, et al.
(författare)
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Tenascin-C and fibronectin in normal esophageal mucosa, Barrett's esophagus, dysplasia and adenocarcinoma
- 2017
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Ingår i: Oncotarget. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1949-2553.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tenascin-C and fibronectin are adhesive glycoproteins modulating the structure of the extracellular matrix and cellular functions. Their expression and function in esophageal adenocarcinoma is poorly known. The aim of this study was to evaluate the expression of tenascin-C and fibronectin in esophageal adenocarcinoma and its precursor stages. RESULTS: Stromal tenascin-C and fibronectin expression were found in all evaluated lesion types. Expression of both molecules increased from gastric metaplasia towards adenocarcinoma (p<0.05). In carcinomas, tenascin-C expression in the bulk was associated with T-stage (p=0.006), presence of lymph node (p=0.004) and distant organ metastases (p=0.007). Abundant tenascin-C expression associated with poor survival (p=0.034) in univariate analysis. Fibronectin expression associated to T-stage (p=0.030). Expression of tenascin-C or fibronectin in the tumor invasive front was not associated to clinicopathological variables or survival. No significant correlation with tumor/stroma percentage, cancer-associated fibroblasts or mean vascular density was observed with either tenascin-C or fibronectin. METHODS: Tenascin-C and fibronectin were stained immunohistochemically and assessed in esophageal specimens from patients with esophageal adenocarcinoma (n=90) or dysplasia (n=30). Structures and lesion were evaluated including normal esophagus (n=77), gastric (n=61) or intestinal (n=51) metaplasia without dysplasia, and low-grade (n=42) or high-grade (n=34) dysplasia, and esophageal adenocarcinoma (n=90). In carcinomas, both bulk and invasive front were separately evaluated. In addition, tumor/stroma percentage, cancer-associated fibroblasts and mean vascular density were evaluated. CONCLUSIONS: Tenascin-C and fibronectin are upregulated in esophageal adenocarcinoma when compared to Barrett's esophagus and dysplasia. Increased tenascin-C expression is associated with metastasis and poor prognosis in esophageal adenocarcinoma.
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| 5. |
- Mäki, Markku, et al.
(författare)
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Prevalence of Celiac disease among children in Finland
- 2003
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 348:25, s. 2517-2524
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Wheat, rye, and barley proteins induce celiac disease, an autoimmune type of gastrointestinal disorder, in genetically susceptible persons. Because the disease may be underdiagnosed, we estimated the prevalence of the disease and tested the hypothesis that assays for serum autoantibodies can be used to detect untreated celiac disease and that positive findings correlate with specific HLA haplotypes.METHODS: Serum samples were collected from 3654 students (age range, 7 to 16 years) in 1994 and screened in 2001 for endomysial and tissue transglutaminase antibodies. HLA typing was also performed on stored blood samples. All antibody-positive subjects were asked to undergo small-bowel biopsy in 2001.RESULTS: Of the 3654 subjects, 56 (1.5 percent) had positive antibody tests, as determined in 2001. Results of the two antibody tests were highly concordant. As of 1994, none of the subjects had received a clinical diagnosis of celiac disease, but 10 who had positive tests for both antibodies in serum obtained in 1994 received the diagnosis between 1994 and 2001. Of the 36 other subjects with positive antibody assays who agreed to undergo biopsy in 2001, 27 had evidence of celiac disease on biopsy. Thus, the estimated biopsy-proved prevalence was 1 case in 99 children. All but two of the antibody-positive subjects had either the HLA-DQ2 or the HLA-DQ8 haplotype. The prevalence of the combination of antibody positivity and an HLA haplotype associated with celiac disease was 1 in 67.CONCLUSIONS: The presence of serum tissue transglutaminase and endomysial autoantibodies is predictive of small-bowel abnormalities indicative of celiac disease. There is a good correlation between autoantibody positivity and specific HLA haplotypes. We estimate that the prevalence of celiac disease among Finnish schoolchildren is at least 1 case in 99 children.
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