| 1. |
- Saarikangas, J, et al.
(författare)
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Missing-in-metastasis MIM/MTSS1 promotes actin assembly at intercellular junctions and is required for integrity of kidney epithelia
- 2011
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Ingår i: Journal of cell science. - : The Company of Biologists. - 1477-9137 .- 0021-9533. ; 124:8Pt 8, s. 1245-1255
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Tidskriftsartikel (refereegranskat)abstract
- MIM/MTSS1 is a tissue-specific regulator of plasma membrane dynamics, whose altered expression levels have been linked to cancer metastasis. MIM deforms phosphoinositide-rich membranes through its I-BAR domain and interacts with actin monomers through its WH2 domain. Recent work proposed that MIM also potentiates Sonic hedgehog (Shh)-induced gene expression. Here, we generated MIM mutant mice and found that full-length MIM protein is dispensable for embryonic development. However, MIM-deficient mice displayed a severe urinary concentration defect caused by compromised integrity of kidney epithelia intercellular junctions, which led to bone abnormalities and end-stage renal failure. In cultured kidney epithelial (MDCK) cells, MIM displayed dynamic localization to adherens junctions, where it promoted Arp2/3-mediated actin filament assembly. This activity was dependent on the ability of MIM to interact with both membranes and actin monomers. Furthermore, results from the mouse model and cell culture experiments suggest that full-length MIM is not crucial for Shh signaling, at least during embryogenesis. Collectively, these data demonstrate that MIM modulates interplay between the actin cytoskeleton and plasma membrane to promote the maintenance of intercellular contacts in kidney epithelia.
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| 2. |
- Savilahti, EM, et al.
(författare)
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Serum 25-Hydroxyvitamin D in Early Childhood Is Nonlinearly Associated with Allergy
- 2016
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 170:3, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Vitamin D has several immunological functions. Data on the relation of vitamin D status and allergy are controversial. <b><i>Methods:</i></b> We investigated the association between serum concentrations of 25-hydroxyvitamin D (25-OHD) and allergy in childhood. The study population (n = 819) was part of a randomized, double-blind, placebo-controlled trial where the mothers of offspring with a high risk for allergy received a mixture of probiotics (or placebo) for the last 4 weeks of pregnancy, and the child received this from birth to 6 months. Study subjects were followed for the emergence of sensitization and allergic symptoms for a period of 5 years, with medical examinations at the ages of 3 and 6 months, 2 and 5 years and also in the event of allergic symptoms. Levels of 25-OHD were measured in umbilical cord blood (UCB) samples (n = 724) and serum samples drawn at the age of 2 years (n = 369); the data were categorized into tertiles (T1-T3) and quartiles (Q1-Q4). The relation between 25-OHD levels and sensitization and allergy was analyzed with multivariable logistic regression analysis. <b><i>Results:</i></b> 25-OHD levels in T2 in UCB were associated with a higher risk for sensitization by the age of 2 years and allergic disorders by the age of 5 years. In the serum samples, at the age of 2 years, 25-OHD levels in Q3 were associated with a higher risk of sensitization and IgE-mediated allergies by the age of 5 years. <b><i>Conclusions:</i></b> The 25-OHD levels in early childhood are associated with the emergence of allergy, but the association appears to be nonlinear.
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| 3. |
- Jalanko, A, et al.
(författare)
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Screening for defined cystic fibrosis mutations by solid-phase minisequencing
- 1992
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Ingår i: Clinical Chemistry. - 0009-9147 .- 1530-8561. ; 38:1, s. 39-43
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a rapid method for the quantitative detection of point mutations and deletions. In this minisequencing method, enzymatically amplified DNA, 5'-biotinylated in one strand, is bound to a solid phase and denatured. A detection primer, constructed to end immediately before the mutation, is annealed to the immobilized single-stranded template and elongated with a single, labeled deoxynucleoside residue. We have applied the solid-phase minisequencing method to the detection of the major mutation, delta F508, causing cystic fibrosis (CF). In the presence of the allele with the delta F508 mutation, [3H]dTTP is incorporated; with the nonmutated allele, [3H]dCTP is incorporated. Thus, samples from heterozygous individuals allow the incorporation of both labels. The method was evaluated by analyzing 59 coded DNA specimens collected from 20 Finnish CF patients and their parents. The ratio of [3H]C to [3H]T gave unambiguously the allele combination. The solid-phase minisequencing method was also applicable to the analysis of three CF mutations simultaneously, i.e., delta F508, G542X, and G551D. We conclude that the microtiter-plate-based minisequencing test is an accurate method for the screening of defined sequence alterations in the CF gene.
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| 4. |
- Knip, Mikael, et al.
(författare)
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Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes The TRIGR Randomized Clinical Trial
- 2018
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Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 319:1, s. 38-48
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes.
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| 5. |
- Lahdenperä, Anna, et al.
(författare)
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Up-regulation of small intestinal interleukin-17 immunity in untreated coeliac disease but not in potential coeliac disease or in type 1 diabetes
- 2012
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Ingår i: Clinical and Experimental Immunology. - : John Wiley & Sons. - 0009-9104 .- 1365-2249. ; 167:2, s. 226-234
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Tidskriftsartikel (refereegranskat)abstract
- Up-regulation of interleukin (IL)-17 in small intestinal mucosa has been reported in coeliac disease (CD) and in peripheral blood in type 1 diabetes (T1D). We explored mucosal IL-17 immunity in different stages of CD, including transglutaminase antibody (TGA)-positive children with potential CD, children with untreated and gluten-free diet-treated CD and in children with T1D. Immunohistochemistry was used for identification of IL-17 and forkhead box protein 3 (FoxP3)-positive cells and quantitative polymerase chain reaction (qPCR) for IL-17, FoxP3, retinoic acid-related orphan receptor (ROR)c and interferon (IFN)-γ transcripts. IL-1β, IL-6 and IL-17 were studied in supernatants from biopsy cultures. Expression of the apoptotic markers BAX and bcl-2 was evaluated in IL-17-stimulated CaCo-2 cells. The mucosal expression of IL-17 and FoxP3 transcripts were elevated in individuals with untreated CD when compared with the TGA-negative reference children, children with potential CD or gluten-free diet-treated children with CD (P andlt; 0·005 for all IL-17 comparisons and P andlt; 0·01 for all FoxP3 comparisons). The numbers of IL-17-positive cells were higher in lamina propria in children with CD than in children with T1D (P andlt; 0·05). In biopsy specimens from patients with untreated CD, enhanced spontaneous secretion of IL-1β, IL-6 and IL-17 was seen. Activation of anti-apoptotic bcl-2 in IL-17-treated CaCo-2 epithelial cells suggests that IL-17 might be involved in mucosal protection. Up-regulation of IL-17 could, however, serve as a biomarker for the development of villous atrophy and active CD.
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| 6. |
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| 7. |
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| 8. |
- Virtanen, S M, et al.
(författare)
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Feasibility and compliance in a nutritional primary prevention trial in infants at increased risk for type 1 diabetes
- 2011
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Ingår i: ACTA PAEDIATRICA. - : Blackwell Publishing Ltd. - 0803-5253. ; 100:4, s. 557-564
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) was launched to determine whether weaning to a highly hydrolysed formula in infancy reduces the incidence of type 1 diabetes in children at increased genetic disease susceptibility. We describe here the findings on feasibility and compliance from the pilot study. Methods: The protocol was tested in 240 children. The diet of the participating children was assessed by self-administered dietary forms, a structured questionnaire and a food record. Blood samples were taken and weight and height measured at birth and at 3, 6, 9, 12, 18 and 24 months. Results: A majority of the subjects (84%) were exposed to the study formula at least for 2 months. Linear growth or weight gain over the first 2 years of life was similar in the two study groups. The levels of IgA and IgG antibodies to cows milk and casein were higher in the cows milk-based formula group than in the hydrolysed formula group during the intervention period (p andlt; 0.05), reflecting the difference in the intake of cows milk protein. Conclusion: This randomized trial on infant feeding turned out to be feasible, and dietary compliance was acceptable. Valuable experience was gained for the planning and sample size estimation of the study proper.
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