↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Träfflista för sökning "WFRF:(Johnny C) "

Sökning: WFRF:(Johnny C)

Resultat 1-50 av 101

Sortera/gruppera träfflistan

Sortering: Träffar per sida:

Numrering	Referens	Omslagsbild	Hitta
1.	2019 Tidskriftsartikel (refereegranskat)
2.	van Essen, TA, et al. (författare) Variation in neurosurgical management of traumatic brain injury: a survey in 68 centers participating in the CENTER-TBI study 2019 Ingår i: Acta neurochirurgica. - : Springer Science and Business Media LLC. - 0942-0940 .- 0001-6268. ; 161:3, s. 435-449 Tidskriftsartikel (refereegranskat)
3.	Cardwell, C R, et al. (författare) Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data 2010 Ingår i: DIABETOLOGIA. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 53:4, s. 641-651 Tidskriftsartikel (refereegranskat)abstract We investigated whether children who are heavier at birth have an increased risk of type 1 diabetes. Relevant studies published before February 2009 were identified from literature searches using MEDLINE, Web of Science and EMBASE. Authors of all studies containing relevant data were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by category of birthweight were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were then used to derive combined ORs and investigate heterogeneity between studies. Data were available for 29 predominantly European studies (five cohort, 24 case-control studies), including 12,807 cases of type 1 diabetes. Overall, studies consistently demonstrated that children with birthweight from 3.5 to 4 kg had an increased risk of diabetes of 6% (OR 1.06 [95% CI 1.01-1.11]; p = 0.02) and children with birthweight over 4 kg had an increased risk of 10% (OR 1.10 [95% CI 1.04-1.19]; p = 0.003), compared with children weighing 3.0 to 3.5 kg at birth. This corresponded to a linear increase in diabetes risk of 3% per 500 g increase in birthweight (OR 1.03 [95% CI 1.00-1.06]; p = 0.03). Adjustments for potential confounders such as gestational age, maternal age, birth order, Caesarean section, breastfeeding and maternal diabetes had little effect on these findings. Children who are heavier at birth have a significant and consistent, but relatively small increase in risk of type 1 diabetes.
4.	Knobler, R., et al. (författare) Guidelines on the use of extracorporeal photopheresis 2014 Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley-Blackwell. - 0926-9959 .- 1468-3083. ; 28:s1, s. 1-37 Tidskriftsartikel (refereegranskat)abstract BackgroundAfter the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma was published in 1983 with its subsequent recognition by the FDA for its refractory forms, the technology has shown significant promise in the treatment of other severe and refractory conditions in a multi-disciplinary setting. Among the major studied conditions are graft versus host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection and inflammatory bowel disease. Materials and methodsIn order to provide recognized expert practical guidelines for the use of this technology for all indications the European Dermatology Forum (EDF) proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. Results and conclusionThese guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion.
5.	Knobler, R., et al. (författare) European dermatology forum : Updated guidelines on the use of extracorporeal photopheresis 2020 - Part 2 2021 Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley-Blackwell Publishing Inc.. - 0926-9959 .- 1468-3083. ; 35:1, s. 27-49 Tidskriftsartikel (refereegranskat)abstract BackgroundFollowing the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T‐cell lymphoma published in 1983, this technology has received continued use and further recognition for additional earlier as well as refractory forms. After the publication of the first guidelines for this technology in the JEADV in 2014, this technology has maintained additional promise in the treatment of other severe and refractory conditions in a multidisciplinary setting. It has confirmed recognition in well‐known documented conditions such as graft‐vs.‐host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection including lung, heart and liver and to a lesser extent inflammatory bowel disease.Materials and methodsIn order to further provide recognized expert practical guidelines for the use of this technology for all indications, the European Dermatology Forum (EDF) again proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. All authors had the opportunity to review each contribution as it was added.Results and conclusionThese updated 2020 guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion. The guidelines were divided into two parts: PART I covers Cutaneous T‐cell lymphoma, chronic graft‐vs.‐host disease and acute graft‐vs.‐host disease, while PART II will cover scleroderma, solid organ transplantation, Crohn’s disease, use of ECP in paediatric patients, atopic dermatitis, type 1 diabetes, pemphigus, epidermolysis bullosa acquisita and erosive oral lichen planus.
6.	Knobler, R., et al. (författare) European dermatology forum - updated guidelines on the use of extracorporeal photopheresis 2020-part 1 2020 Ingår i: Journal of the European Academy of Dermatology and Venereology. - : WILEY. - 0926-9959 .- 1468-3083. ; 34:12, s. 2693-2716 Tidskriftsartikel (refereegranskat)abstract Background Following the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma published in 1983, this technology has received continued use and further recognition for additional earlier as well as refractory forms. After the publication of the first guidelines for this technology in the JEADV in 2014, this technology has maintained additional promise in the treatment of other severe and refractory conditions in a multi-disciplinary setting. It has confirmed recognition in well-known documented conditions such as graft-versus-host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection including lung, heart and liver and to a lesser extent inflammatory bowel disease. Materials and methods In order to further provide recognized expert practical guidelines for the use of this technology for all indications, the European Dermatology Forum (EDF) again proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. All authors had the opportunity to review each contribution as it was added. Results and conclusion These updated 2020 guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion. The guidelines are divided in two parts: PART I covers cutaneous T-cell lymphoma, chronic graft-versus-host disease and acute graft-versus-host disease while PART II will cover scleroderma, solid organ transplantation, Crohns disease, use of ECP in paediatrics practice, atopic dermatitis, type 1 diabetes, pemphigus, epidermolysis bullosa acquisita and erosive oral lichen planus.
7.	Sonnenschein-van der Voort, Agnes M. M, et al. (författare) Preterm birth, infant weight gain, and childhood asthma risk: A meta-analysis of 147,000 European children 2014 Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 133:5, s. 1317-1329 Tidskriftsartikel (refereegranskat)abstract Background: Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results. Objectives: We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years). Methods: First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age less than 37 weeks) and low birth weight (less than 2500 g) with childhood asthma outcomes. Results: Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P less than. 05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27). Conclusion: Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth.
8.	Bybrant, M. C., et al. (författare) Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes 2021 Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 22:3, s. 417-424 Tidskriftsartikel (refereegranskat)abstract Objectives Children with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti-tTG) that were >= 10 times the upper limit of normal (10x ULN) predicted CD in T1D. Methods Data from the Swedish prospective Better Diabetes Diagnosis study was used, and 2035 children and adolescents with T1D diagnosed between 2005-2010 were included. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti-tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti-tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh-Oberhuber classification. Results All of the 60 children with anti-tTG >= 10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti-tTG levels. Among 2003 screened children, 6.9% had positive anti-tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2035). All but one of the children diagnosed with CD had HLA-DQ2 and/or DQ8. Conclusions As all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a noninvasive method.
9.	Cardwell, Chris R, et al. (författare) Birth order and childhood type 1 diabetes risk: a pooled analysis of 31 observational studies 2011 Ingår i: INTERNATIONAL JOURNAL OF EPIDEMIOLOGY. - : OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND. - 0300-5771 .- 1464-3685. ; 40:2, s. 363-374 Tidskriftsartikel (refereegranskat)abstract Background The incidence rates of childhood onset type 1 diabetes are almost universally increasing across the globe but the aetiology of the disease remains largely unknown. We investigated whether birth order is associated with the risk of childhood diabetes by performing a pooled analysis of previous studies. Methods Relevant studies published before January 2010 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies provided individual patient data or conducted pre-specified analyses. Meta-analysis techniques were used to derive combined odds ratios (ORs), before and after adjustment for confounders, and investigate heterogeneity. Results Data were available for 6 cohort and 25 case-control studies, including 11 955 cases of type 1 diabetes. Overall, there was no evidence of an association prior to adjustment for confounders. After adjustment for maternal age at birth and other confounders, a reduction in the risk of diabetes in second- or later born children became apparent [fully adjusted OR = 0.90 95% confidence interval (CI) 0.83-0.98; P = 0.02] but this association varied markedly between studies (I-2 = 67%). An a priori subgroup analysis showed that the association was stronger and more consistent in children andlt; 5 years of age (n = 25 studies, maternal age adjusted OR = 0.84 95% CI 0.75, 0.93; I-2 = 23%). Conclusion Although the association varied between studies, there was some evidence of a lower risk of childhood onset type 1 diabetes with increasing birth order, particularly in children aged andlt; 5 years. This finding could reflect increased exposure to infections in early life in later born children.
10.	Cardwell, Chris R, et al. (författare) Breast-Feeding and Childhood-Onset Type 1 Diabetes A pooled analysis of individual participant data from 43 observational studies 2012 Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 35:11, s. 2215-2225 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE-To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. less thanbrgreater than less thanbrgreater thanRESEARCH DESIGN AND METHODS-Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies. less thanbrgreater than less thanbrgreater thanRESULTS-Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for andgt;2 weeks (20 studies; OR = 0.75, 95% CI 0.64-0.88), the association after exclusive breast-feeding for andgt;3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75-1.00), and no association was observed after (nonexclusive) breast-feeding for andgt;2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or andgt;3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I-2 = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for andgt;2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I-2 = 0%). Adjustments for potential confounders altered these estimates very little. less thanbrgreater than less thanbrgreater thanCONCLUSIONS-The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.
11.	Cardwell, Chris R, et al. (författare) Maternal Age at Birth and Childhood Type 1 Diabetes: A Pooled Analysis of 30 Observational Studies 2010 Ingår i: DIABETES. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 59:2, s. 486-494 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE-The aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized confounders. RESEARCH DESIGN AND METHODS-Relevant studies published before June 2009 were identified from MEDLINE, Web of Science, and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct prespecified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios and to investigate heterogeneity among studies. RESULTS-Data were available for 5 cohort and 25 case-control studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2-9) increase in childhood type 1 diabetes odds per 5-year increase in maternal age (P = 0.006), but there was heterogeneity among studies (heterogeneity I-2 = 70%). In studies with a low risk of bias, there was a more marked increase in diabetes odds of 10% per 5-year increase in maternal age. Adjustments for potential confounders little altered these estimates. CONCLUSIONS-There was evidence of a weak but significant linear increase in the risk of childhood type 1 diabetes across the range of maternal ages, but the magnitude of association varied between studies. A very small percentage of the increase in the incidence of childhood type 1 diabetes in recent years could be explained by increases in maternal age.
12.	Gyllenberg, A, et al. (författare) Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes 2012 Ingår i: Genes and Immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 76:2, s. 202-203 Tidskriftsartikel (refereegranskat)abstract The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P=4 × 10(-5) and rs3087456, P=0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P=0.006, P=0.007). We also detect association to T1D for both markers, rs11074932 (P=0.004) and rs3087456 (P=0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.
13.	Tatovic, D, et al. (författare) Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes 2022 Ingår i: Immunotherapy Advances. - : Oxford University Press (OUP). - 2732-4303. ; 2:1 Tidskriftsartikel (refereegranskat)abstract Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune β-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies.
14.	Andersson, C, et al. (författare) Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes 2013 Ingår i: Pediatric Diabetes. - : Wiley-Blackwell. - 1399-543X .- 1399-5448. ; 14:2, s. 97-105 Tidskriftsartikel (refereegranskat)abstract Andersson C, Vaziri-Sani F, Delli AJ, Lindblad B, Carlsson A, Forsander G, Ludvigsson J, Marcus C, Samuelsson U, Ivarsson SA, Lernmark A, Elding Larsson H, the BDD Study group. Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes. Pediatric Diabetes 2013: 14: 97-105. Objective To establish the diagnostic sensitivity of and the relationships between autoantibodies to all three Zinc transporter 8 (Zinc transporter 8 autoantibody to either one, two, or all three amino acid variants at position 325, ZnT8A) variants to human leukocyte antigen (HLA)-DQ and to autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A), and insulin (IAA). Methods We analyzed 3165 patients with type 1 diabetes (T1D) in the Better Diabetes Diagnosis study for HLA-DQ genotypes and all six autoantibodies (ZnT8RA, arginine 325 Zinc transporter 8 autoantibody; ZnT8WA, tryptophan 325 Zinc transporter 8 autoantibody; ZnT8QA, glutamine 325 Zinc transporter 8 autoantibody; GADA, IA-2A, and IAA). Results ZnT8A was found in 65% of the patients and as many as 108 of 3165 (3.4%) had 13 ZnT8A alone. None had ZnT8QA alone. Together with GADA (56%), IA-2A (73%), and IAA (33%), 93% of the T1D patients were autoantibody positive. All three ZnT8A were less frequent in children below 2 yr of age (pandlt;0.0001). All three ZnT8A were associated with DQA1-B1X-0604 (DQ6.4) and DQA1-B103-0302 (DQ8). ZnT8WA and ZnT8QA were negatively associated with DQA1-B1*05-02 (DQ2). Conclusions Analysis of ZnT8A increased the diagnostic sensitivity of islet autoantibodies for T1D as only 7% remained islet autoantibody negative. The association between DQ6.4 and all three ZnT8A may be related to ZnT8 antigen presentation by the DQ6.4 heterodimer.
15.	Bybrant, M. C., et al. (författare) Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study 2018 Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 51:5, s. 221-227 Tidskriftsartikel (refereegranskat)abstract Objectives: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D).Patients and methods: Dried blood spots and serum samples were taken at diagnosis from children <18years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA).Results: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p=.00001) and those with DQX/X (p.00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p=.018).Conclusion: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD.
16.	Cardwell, Chris R, et al. (författare) Interbirth Interval Is Associated With Childhood Type 1 Diabetes Risk 2012 Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:3, s. 702-707 Tidskriftsartikel (refereegranskat)abstract Short interbirth interval has been associated with maternal complications and childhood autism and leukemia, possibly due to deficiencies in maternal micronutrients at conception or increased exposure to sibling infections. A possible association between interbirth interval and subsequent risk of childhood type 1 diabetes has not been investigated. A secondary analysis of 14 published observational studies of perinatal risk factors for type 1 diabetes was conducted. Risk estimates of diabetes by category of interbirth interval were calculated for each study. Random effects models were used to calculate pooled odds ratios (ORs) and investigate heterogeneity between studies. Overall, 2,787 children with type 1 diabetes were included. There was a reduction in the risk of childhood type 1 diabetes in children born to mothers after interbirth intervals andlt;3 years compared with longer interbirth intervals (OR 0.82 [95% CI 0.72-0.93]). Adjustments for various potential confounders little altered this estimate. In conclusion, there was evidence of a 20% reduction in the risk of childhood diabetes in children born to mothers after interbirth intervals andlt;3 years.
17.	Hu, Xiping, et al. (författare) SAfeDJ : A crowd-cloud codesign approach to situation-aware music delivery for drivers 2015 Ingår i: ACM Transactions on Multimedia Computing, Communications, and Applications (TOMCCAP). - : Association for Computing Machinery (ACM). - 1551-6857 .- 1551-6865. ; 12:1s, s. 21:1-24 Tidskriftsartikel (refereegranskat)abstract Driving is an integral part of our everyday lives, but it is also a time when people are uniquely vulnerable. Previous research has demonstrated that not only does listening to suitable music while driving not impair driving performance, but it could lead to an improved mood and a more relaxed body state, which could improve driving performance and promote safe driving significantly. In this article, we propose SAfeDJ, a smartphone-based situation-aware music recommendation system, which is designed to turn driving into a safe and enjoyable experience. SAfeDJ aims at helping drivers to diminish fatigue and negative emotion. Its design is based on novel interactive methods, which enable in-car smartphones to orchestrate multiple sources of sensing data and the drivers' social context, in collaboration with cloud computing to form a seamless crowdsensing solution. This solution enables different smartphones to collaboratively recommend preferable music to drivers according to each driver's specific situations in an automated and intelligent manner. Practical experiments of SAfeDJ have proved its effectiveness in music-mood analysis, and mood-fatigue detections of drivers with reasonable computation and communication overheads on smartphones. Also, our user studies have demonstrated that SAfeDJ helps to decrease fatigue degree and negative mood degree of drivers by 49.09% and 36.35%, respectively, compared to traditional smartphone-based music player under similar driving situations.
18.	Kwan, Johnny S H, et al. (författare) Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels. 2014 Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6684-93 Tidskriftsartikel (refereegranskat)abstract Osteoprotegerin (OPG) is involved in bone homeostasis and tumor cell survival. Circulating OPG levels are also important biomarkers of various clinical traits, such as cancers and atherosclerosis. OPG levels were measured in serum or in plasma. In a meta-analysis of genome-wide association studies in up to 10,336 individuals from European and Asian origin, we discovered that variants >100 Kb upstream of the TNFRSF11B gene encoding OPG and another new locus on chromosome 17q11.2 were significantly associated with OPG variation. We also identified a suggestive locus on chromosome 14q21.2 associated with the trait. Moreover, we estimated that over half of the heritability of OPG levels could be explained by all variants examined in our study. Our findings provide further insight into the genetic regulation of circulating OPG levels.
19.	Ludvigsson, Johnny, et al. (författare) Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial 2021 Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:7, s. 1604-1612 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE To evaluate the efficacy of aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy combined with vitamin D supplementation in preserving endogenous insulin secretion in all patients with type 1 diabetes (T1D) or in a genetically prespecified subgroup. RESEARCH DESIGN AND METHODS In a multicenter, randomized, placebo-controlled, double-blind trial, 109 patients aged 12-24 years (mean +/- SD 16.4 +/- 4.1) with a diabetes duration of 7-193 days (88.8 +/- 51.4), elevated serum GAD65 autoantibodies, and a fasting serum C-peptide >0.12 nmol/L were recruited. Participants were randomized to receive either three intralymphatic injections (1 month apart) with 4 mu g GAD-alum and oral vitamin D (2,000 IE daily for 120 days) or placebo. The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15 months. RESULTS Primary end point was not met in the full analysis set (treatment effect ratio 1.091 [CI 0.845-1.408]; P = 0.5009). However, GAD-alum-treated patients carrying HLA DR3-DQ2 (n = 29; defined as DRB103, DQB102:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557 [CI 1.126-2.153]; P = 0.0078) after 15 months compared with individuals receiving placebo with the same genotype (n = 17). Several secondary end points showed supporting trends, and a positive effect was seen in partial remission (insulin dose-adjusted HbA(1c) <= 9; P = 0.0310). Minor transient injection site reactions were reported. CONCLUSION Intralymphatic administration of GAD-alum is a simple, well-tolerated treatment that together with vitamin D supplementation seems to preserve C-peptide in patients with recent-onset T1D carrying HLA DR3-DQ2. This constitutes a disease-modifying treatment for T1D with a precision medicine approach.
20.	Nowak, C., et al. (författare) Intralymphatic GAD-Alum (Diamyd (R)) Improves Glycemic Control in Type 1 Diabetes With HLA DR3-DQ2 2022 Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:9, s. 2644-2651 Tidskriftsartikel (refereegranskat)abstract Aims Residual beta cell function in type 1 diabetes (T1D) is associated with lower risk of complications. Autoantigen therapy with GAD-alum (Diamyd) given in 3 intralymphatic injections with oral vitamin D has shown promising results in persons with T1D carrying the human leukocyte antigen (HLA) DR3-DQ2 haplotype in the phase 2b trial DIAGNODE-2. We aimed to explore the efficacy of intralymphatic GAD-alum on blood glucose recorded by continuous glucose monitoring (CGM). Methods DIAGNODE-2 (NCT03345004) was a multicenter, randomized, placebo-controlled, double-blind trial of 109 recent-onset T1D patients aged 12 to 24 years with GAD65 antibodies and fasting C-peptide > 0.12 nmol/L, which randomized patients to 3 intralymphatic injections of 4 mu g GAD-alum and oral vitamin D, or placebo. We report results for exploratory endpoints assessed by 14-day CGM at months 0, 6, and 15. Treatment arms were compared by mixed-effects models for repeated measures adjusting for baseline values. Results We included 98 patients with CGM recordings of sufficient quality (DR3-DQ2-positive patients: 27 GAD-alum-treated and 15 placebo-treated). In DR3-DQ2-positive patients, percent of time in range (TIR, 3.9-10 mmol/L) declined less between baseline and month 15 in GAD-alum-treated compared with placebo-treated patients (-5.1% and -16.7%, respectively; P = 0.0075), with reduced time > 13.9 mmol/L (P = 0.0036), and significant benefits on the glucose management indicator (P = 0.0025). No differences were detected for hypoglycemia. GAD-alum compared to placebo lowered the increase in glycemic variability (standard deviation) observed in both groups (P = 0.0219). Change in C-peptide was correlated with the change in TIR. Conclusions Intralymphatic GAD-alum improves glycemic control in recently diagnosed T1D patients carrying HLA DR3-DQ2.
21.	Onengut-Gumuscu, Suna, et al. (författare) Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers. 2015 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47:4, s. 381-386 Tidskriftsartikel (refereegranskat)abstract Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility regions, finding major pathways contributing to risk, with some loci shared across immune disorders. To make genetic comparisons across autoimmune disorders as informative as possible, a dense genotyping array, the Immunochip, was developed, from which we identified four new T1D-associated regions (P < 5 × 10(-8)). A comparative analysis with 15 immune diseases showed that T1D is more similar genetically to other autoantibody-positive diseases, significantly most similar to juvenile idiopathic arthritis and significantly least similar to ulcerative colitis, and provided support for three additional new T1D risk loci. Using a Bayesian approach, we defined credible sets for the T1D-associated SNPs. The associated SNPs localized to enhancer sequences active in thymus, T and B cells, and CD34(+) stem cells. Enhancer-promoter interactions can now be analyzed in these cell types to identify which particular genes and regulatory sequences are causal.
22.	Persson, M., et al. (författare) The Better Diabetes Diagnosis (BDD) study – A review of a nationwide prospective cohort study in Sweden 2018 Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 140, s. 236-244 Forskningsöversikt (refereegranskat)abstract The incidence of type 1 diabetes (T1D) in Sweden is one of the highest in the world. However, the possibility of other types of diabetes must also be considered. In addition, individuals with T1D constitute a heterogeneous group. A precise classification of diabetes is a prerequisite for optimal outcome. For precise classification, knowledge on the distribution of genetic factors, biochemical markers and clinical features in individuals with new onset of diabetes is needed. The Better Diabetes Diagnosis (BDD), is a nationwide study in Sweden with the primary aim to facilitate a more precise classification and diagnosis of diabetes in order to enable the most adequate treatment for each patient. Secondary aims include identification of risk factors for diabetes-related co-morbidities. Since 2005, data on almost all children and adolescents with newly diagnosed diabetes in Sweden are prospectively collected and including heredity of diabetes, clinical symptoms, levels of C peptide, genetic analyses and detection of autoantibodies. Since 2011, analyses of HLA profile, autoantibodies and C peptide levels are part of clinical routine in Sweden for all pediatric patients with suspected diagnosis of diabetes. In this review, we present the methods and main results of the BDD study so far and discuss future aspects.
23.	Sedimbi, S. K., et al. (författare) SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients 2007 Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21 Tidskriftsartikel (refereegranskat)abstract SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
24.	Shin, J. H., et al. (författare) IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5 2007 Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12 Tidskriftsartikel (refereegranskat)abstract In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A10501-B10201 haplotypes (P=2.4 x 10(-5)) and DQ A10301-B10302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
25.	Stalder, J-F, et al. (författare) Patient-Oriented SCORAD (PO-SCORAD): a new self-assessment scale in atopic dermatitis validated in Europe. 2011 Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 66, s. 1114-1121 Tidskriftsartikel (refereegranskat)abstract To cite this article: Stalder J-F, Barbarot S, Wollenberg A, Holm EA, De Raeve L, Seidenari S, Oranje A, Deleuran M, Cambazard F, Svensson A, Simon D, Benfeldt E, Reunala T, Mazereeuv J, Boralevi F, Kunz B, Misery L, Mortz CG, Darsow U, Gelmetti C, Diepgen T, Ring J, Moehrenschlager M, Gieler U, Taïeb A, for the PO-SCORAD Investigators Group. Patient-Oriented SCORAD (PO-SCORAD): a new self-assessment scale in atopic dermatitis validated in Europe. Allergy 2011; DOI: 10.1111/j.1398-9995.2011.02577.x. ABSTRACT: Background: Patient-oriented medicine is an emerging concept, encouraged by the World Health Organization, to greater involvement of the patient in the management of chronic diseases. The Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD) index is a self-assessment score allowing the patient to comprehensively evaluate the actual course of atopic dermatitis (AD), using subjective and objective criteria derived mainly from the SCORAD, a validated AD severity clinical assessment tool. Objectives: To validate the PO-SCORAD index in a large European population of patients exhibiting all forms of AD severity by assessing its correlation with the SCORAD index. Patients/methods: Four hundred and seventy-one patients (185 adults, 286 children) consulting for AD in hospitals from 9 European countries were recruited. The investigators and the patients used the SCORAD and PO-SCORAD scales, respectively, to assess AD severity at inclusion (D0) and 28 ± 7 days later (D28). Results: Patient-Oriented SCORing Atopic Dermatitis and SCORAD scores were significantly correlated at D0 [r = 0.67 (95% CI: 0.62; 0.72), P < 0.0001]. Consistency was confirmed at D28, with a stronger linear correlation between both scales [r = 0.79 (95% CI: 0.75; 0.83), P < 0.0001]. Absolute changes from baseline in SCORAD and PO-SCORAD scores were also significantly correlated [r= 0.71 (95% CI: 0.64; 0.76), P < 0.0001]. Although no specific intervention was investigated, AD improved over the study, with a decrease of PO-SCORAD and SCORAD scores from D0 to D28 by -19.19% and -24.39%, respectively. The consistency of the correlations was similar in the adult and children groups. Conclusions: This study validated the use of PO-SCORAD to self-assess AD severity and demonstrated its good correlation with SCORAD.
26.	van Meel, Evelien R., et al. (författare) Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children 2022 Ingår i: European Respiratory Journal. - : EUROPEAN RESPIRATORY SOC JOURNALS LTD. - 0903-1936 .- 1399-3003. ; 60:4 Tidskriftsartikel (refereegranskat)abstract Background Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. Methods We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. Results Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. Conclusions Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections.
27.	Arnqvist, Hans, et al. (författare) Impact of HbA(1c) Followed 32 Years From Diagnosis of Type 1 Diabetes on Development of Severe Retinopathy and Nephropathy: The VISS Study 2022 Ingår i: Diabetes Care. - : AMER DIABETES ASSOC. - 0149-5992 .- 1935-5548. ; 45:11, s. 2675-2682 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE To evaluate HbA(1c) followed from diagnosis, as a predictor of severe microvascular complications (i.e., proliferative diabetic retinopathy [PDR] and nephropathy [macroalbuminuria]). RESEARCH DESIGN AND METHODS In a population-based observational study, 447 patients diagnosed with type 1 diabetes before 35 years of age from 1983 to 1987 in southeast Sweden were followed from diagnosis until 2019. Long-term weighted mean HbA(1c) (wHbA(1c)) was calculated by integrating the area under all HbA(1c) values. Complications were analyzed in relation to wHbA(1c) categorized into five levels. RESULTS After 32 years, 9% had no retinopathy, 64% non-PDR, and 27% PDR, and 83% had no microalbuminuria, 9% microalbuminuria, and 8% macroalbuminuria. Patients with near-normal wHbA(1c) did not develop PDR or macroalbuminuria. The lowest wHbA(1c) values associated with development of PDR and nephropathy (macroalbuminuria) were 7.3% (56 mmol/mol) and 8.1% (65 mmol/mol), respectively. The prevalence of PDR and macroalbuminuria increased with increasing wHbA(1c), being 74% and 44% in the highest category, wHbA(1c) >9.5% (>80 mmol/mol). In comparison with the follow-up done after 20-24 years duration, the prevalence of PDR had increased from 14 to 27% and macroalbuminuria from 4 to 8%, and both appeared at lower wHbA(1c) values. CONCLUSIONS wHbA(1c) followed from diagnosis is a very strong biomarker for PDR and nephropathy, the prevalence of both still increasing 32 years after diagnosis. To avoid PDR and macroalbuminuria in patients with type 1 diabetes, an HbA(1c) <7.0% (53 mmol/mol) and as normal as possible should be recommended when achievable without severe hypoglycemia and with good quality of life.
28.	Aydemir, O, et al. (författare) Genetic Variation Within the HLA-DRA1 Gene Modulates Susceptibility to Type 1 Diabetes in HLA-DR3 Homozygotes 2019 Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 68:7, s. 1523-1527 Tidskriftsartikel (refereegranskat)abstract Type 1 diabetes (T1D) involves the interaction of multiple gene variants, environmental factors, and immunoregulatory dysfunction. Major T1D genetic risk loci encode HLA-DR and -DQ. Genetic heterogeneity and linkage disequilibrium in the highly polymorphic HLA region confound attempts to identify additional T1D susceptibility loci. To minimize HLA heterogeneity, T1D patients (N = 365) and control subjects (N = 668) homozygous for the HLA-DR3 high-risk haplotype were selected from multiple large T1D studies and examined to identify new T1D susceptibility loci using molecular inversion probe sequencing technology. We report that risk for T1D in HLA-DR3 homozygotes is increased significantly by a previously unreported haplotype of three single nucleotide polymorphisms (SNPs) within the first intron of HLA-DRA1. The homozygous risk haplotype has an odds ratio of 4.65 relative to the protective homozygous haplotype in our sample. Individually, these SNPs reportedly function as “expression quantitative trait loci,” modulating HLA-DR and -DQ expression. From our analysis of available data, we conclude that the tri-SNP haplotype within HLA-DRA1 may modulate class II expression, suggesting that increased T1D risk could be attributable to regulated expression of class II genes. These findings could help clarify the role of HLA in T1D susceptibility and improve diabetes risk assessment, particularly in high-risk HLA-DR3 homozygous individuals.
29.	Barker, A., et al. (författare) Age-dependent decline of beta-cell function in type 1 diabetes after diagnosis: a multi-centre longitudinal study 2014 Ingår i: Diabetes, obesity and metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 16:3, s. 262-267 Tidskriftsartikel (refereegranskat)abstract AimsC-peptide secretion is currently the only available clinical biomarker to measure residual -cell function in type 1 diabetes. However, the natural history of C-peptide decline after diagnosis can vary considerably dependent upon several variables. We investigated the shape of C-peptide decline over time from type 1 diabetes onset in relation to age at diagnosis, haemoglobin A1c (HbA1c) levels and insulin dose. MethodsWe analysed data from 3929 type 1 diabetes patients recruited from seven European centres representing all age groups at disease onset (childhood, adolescence and adulthood). The influence of the age at onset on -cell function was investigated in a longitudinal analysis at diagnosis and up to 5-years follow-up. ResultsFasting C-peptide (FCP) data at diagnosis were available in 3668 patients stratified according to age at diagnosis in four groups (less than5years, n=344; greater than5yearsless than10years, n=668; greater than10yearsless than18years, n=991; greater than18years, n=1655). FCP levels were positively correlated with age (pless than0.001); the subsequent decline in FCP over time was log-linear with a greater decline rate in younger age groups (pless than0.0001). ConclusionsThis study reveals a positive correlation between age at diagnosis of type 1 diabetes and FCP with a more rapid decline of -cell function in the very young patients. These data can inform the design of clinical trials using C-peptide values as an end-point for the effect of a given treatment.
30.	Beam, Craig A., et al. (författare) GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings from a Bayesian meta-analysis 2017 Ingår i: Diabetologia. - : SPRINGER. - 0012-186X .- 1432-0428. ; 60:1, s. 43-49 Tidskriftsartikel (refereegranskat)abstract GAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results. In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-peptide could be reached by combining individual-level data from the randomised controlled trials using Bayesian meta-analysis to estimate the probability of a positive biological effect (a reduction in C-peptide loss compared with placebo approximately 1 year after the GAD vaccine). We estimate that there is a 98% probability that 20 mu g GAD with alum administered twice yields a positive biological effect. The effect is probably a 15-20% reduction in the loss of C-peptide at approximately 1 year after treatment. This translates to an annual expected loss of between -0.250 and -0.235 pmol/ml in treated patients compared with an expected 2 h AUC loss of -0.294 pmol/ml at 1 year for untreated newly diagnosed patients. The biological effect of this vaccination should be developed further in order to reach clinically desirable reductions in insulin loss in patients recently diagnosed with type 1 diabetes.
31.	Berzina, L., et al. (författare) DR3 is associated with type 1 diabetes and blood group ABO incompatibility 2002 Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 958, s. 345-348 Tidskriftsartikel (refereegranskat)abstract Type 1 diabetes is associated with autoimmunity against pancreatic β cells. ABO incompatibility is associated with ABO immunization during pregnancy. Type 1 diabetes is associated with certain HLA DR and DQ haplotypes. The mechanism by which blood group incompatibility is associated with the risk of type 1 diabetes is not known. We propose that certain HLA alleles contribute to the development of both type 1 diabetes and ABO blood group incompatibility. We studied 57 children with ABO blood group incompatibility, 118 children with type 1 diabetes, and 98 age- and sex-matched unrelated healthy controls from Linköping. Typing of HLA DQA1, DQB1, and DRB1 was done on DNA extracted from peripheral blood, by PCR amplification, manual dot-blotting onto nylon membranes, synthetic sequence-specific oligonucleotide (SSO) probe 3′ end-labeling with 32P-dCTP, and hybridization followed by stringency washes and autoradiography. We observed that DR3 allele was more frequent in patients with ABO incompatibility when compared to healthy controls (OR = 2.7, Pc < 0.05). Patients with type 1 diabetes had significantly higher frequency of DR3, DQ2, DR4, and DQ8 alleles when compared to healthy controls. No significant difference was observed in frequency of DR3 between ABO blood group incompatibility and type 1 diabetes patients. We conclude that DR3 is associated with both the development of type 1 diabetes and ABO incompatibility.
32.	Besser, Rachel E. J., et al. (författare) Exploring C-peptide loss in type 1 diabetes using growth curve analysis 2018 Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 13:7 Tidskriftsartikel (refereegranskat)abstract Objectives C-peptide (CP) loss in type 1 diabetes (T1D) is highly variable, and factors influencing it are poorly understood. We modelled CP values in T1D patients from diagnosis for up to 6 years, treating the serial data as growth curves plotted against time since diagnosis. The aims were to summarise the pattern of CP loss (i.e. growth curve shape) in individual patients in simple terms, and to identify baseline characteristics that predict this pattern in individuals. Materials and methods Between 1976 and 2011, 442 T1D patients initially aged amp;lt; 18y underwent 120-minute mixed meal tolerance tests (MMTT) to calculate area under the curve (AUC) CP, at 3, 9,18, 30, 48 and 72 months after diagnosis (n = 1537). The data were analysed using the novel SITAR mixed effects growth curve model (Superlmposition by Translation And Rotation). It fits a mean AUC growth curve, but also allows the curves mean level and rate of fall to vary between individuals so as to best fit the individual patient curves. These curve adjustments define individual curve shape. Results The square root (root) AUC scale provided the best fit. The mean levels and rates of fall for individuals were normally distributed and uncorrelated with each other. Age at diagnosis and root AUC at 3 months strongly predicted the patient-specific mean levels, while younger age at diagnosis (p amp;lt; 0.0001) and the 120-minute CP value of the 3-month MMTT (p = 0.002) predicted the patient-specific rates of fall. Conclusions SITAR growth curve analysis is a useful tool to assess CP loss in type 1 diabetes, explaining patient differences in terms of their mean level and rate of fall. A definition of rapid CP loss could be based on a quantile of the rate of fall distribution, allowing better understanding of factors determining CP loss and stratification of patients into targeted therapies.
33.	Björck, Martin, et al. (författare) Plasminogen Activator Inhibitor-1 Levels and Activity Decrease After Intervention in Patients with Critical Limb Ischaemia 2013 Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 46:2, s. 214-222 Tidskriftsartikel (refereegranskat)abstract Patients with peripheral arterial occlusive disease (PAOD), in particular critical limb ischaemia (CLI), carry a high risk of thrombotic events. We hypothesised that patients undergoing conservative, endovascular, or open surgical treatment for CLI have increased levels of plasminogen activator inhibitor-1 (PAI-1), leading to a prothrombotic state. The objective was to determine levels of PAI-1 in patients with acute or chronic PAOD/CLI. Thirty-two patients with a median age of 74 (49–90) years were included. Three underwent thrombolysis for acute limb-threatening ischaemia. Twenty-six patients with chronic ischaemia received endovascular (n = 20) or open (n = 6) surgical treatment. Three were treated conservatively. Biomarkers and ankle brachial index (ABI) were measured before and up to 1 month after intervention. Patency was studied with repeated duplex ultrasound. Ankle pressure and ABI improved after intervention (p < .001). C-reactive protein (CRP) increased from a median of 7.90 mg/L at baseline to 31.5 on day 1 (p < .001), 28.0 on day 6 (p < .001), and returned to baseline levels on day 30. PAI-1 antigen and activity decreased from day 6 and onwards post-intervention compared with baseline (p < .05). A great individual variability in PAI-1 antigen and activity was observed. Although most actively treated patients had normal PAI-1 activity, 11/29 (38%) were above that level of normality at baseline, 10/24 (42%) on day 1, 3/23 (13%) on day 6, and 5/27 (19%) on day 30 after intervention. Endovascular and open surgical treatment resulted in improved ankle pressure and ABI. The intervention was followed by a transient increase in CRP and a sustained reduction in PAI-1 levels and activity.
34.	Bustad, Johnny, et al. (författare) C1s and O1s gas phase shake-up spectra from Mo(CO)6 1994 Ingår i: Chemical Physics. - : Elsevier BV. - 0301-0104 .- 1873-4421. ; 179:3, s. 303-312 Tidskriftsartikel (refereegranskat)abstract Experimental high-resolution core photoelectron C1s and O1s shake-up spectra of molybdenum hexacarbonyl, Mo(CO)(6), are reported and compared with results of semiempirical INDO/CI calculations. Several hitherto unobserved peaks are identified and assigned. It is found that an intra- and inter-group classification can be used to describe the transitions. The transitions of lowest energy have Mo-CO inter-group character. Dynamical effects on the line widths of the experimental shake-up peaks are discussed. A discussion of the relevance of experimental results obtained for the Mo(CO)(6)e for CO adsorption on metal surfaces is presented.
35.	Bustad, Johnny, et al. (författare) Semi-empirical configurational interaction calculation of shake-up satellites in Ni(CO)4 1998 Ingår i: International Journal of Quantum Chemistry. - 0020-7608 .- 1097-461X. ; 69:5, s. 649-657 Tidskriftsartikel (refereegranskat)abstract INDO/CI calculations were used to analyze the C1s and O1s shake-up spectra of nickel tetracarbonyl, Ni(CO)4. The satellite structure in both cases is dominated by excitations from metal–ligand bonding (2Πb) to metal–ligand antibonding (2Πa) orbitals and by excitations within the core-ionized CO molecule, ΠCO—Π*CO.
36.	Bustad, Johnny, et al. (författare) Theoretical study of core ionized Cr(CO)6 1995 Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - 0368-2048 .- 1873-2526. ; 70:3, s. 233-244 Tidskriftsartikel (refereegranskat)abstract The satellite structure of the Cls and Ols photoelectron spectra of chromium hexacarbonyl Cr(CO)(6) has been calculated by the INDO/CI method and compared with available high resolution core level photoelectron spectra. A reassignment of some of the lines is made. It is found that the satellite structure in both cases is dominated by excitations from metal-ligand bonding to metal-ligand antibonding Me(3d)-pi* orbitals, and that these shake-up excitations involve a significant charge transfer to the core ionized ligand from the rest of the molecule.
37.	Carlsson, Annelie, et al. (författare) Low risk HLA-DQ and increased body mass index in newly diagnosed type 1 diabetes children in the Better Diabetes Diagnosis study in Sweden 2012 Ingår i: International Journal of Obesity. - : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 36:5, s. 718-724 Tidskriftsartikel (refereegranskat)abstract Objective: Type 1 diabetes and obesity has increased in childhood. We therefore tested the hypothesis that type 1 diabetes human leukocyte antigen DQ (HLA-DQ) risk genotypes may be associated with increased body mass index (BMI). less thanbrgreater than less thanbrgreater thanDesign: The type 1 diabetes high-risk HLA-DQ A105:01-B102:01/A103:01-B103:02 genotype along with lower risk DQ genotypes were determined at the time of clinical onset by PCR and hybridization with allele-specific probes. BMI was determined after diabetes was stabilized. less thanbrgreater than less thanbrgreater thanSubjects: A total of 2403 incident type 1 diabetes children below 18 years of age were ascertained in the Swedish national Better Diabetes Diagnosis (BDD) study between May 2005 to September 2009. All children classified with type 1 diabetes, including positivity for at least one islet autoantibody, were investigated. less thanbrgreater than less thanbrgreater thanResults: Overall, type 1 diabetes HLA-DQ risk was negatively associated with BMI (Pandlt;0.0008). The proportion of the highest risk A105:01-B102:01/A103:01-B103:02 genotype decreased with increasing BMI (Pandlt;0.0004). However, lower risk type 1 diabetes DQ genotypes were associated with an increased proportion of patients who were overweight or obese (Pandlt;0.0001). Indeed, the proportion of patients with the low-risk A105:01-B102:01/A105:01-B102:01 genotype increased with increasing BMI (Pandlt;0.003). The magnitude of association on the multiplicative scale between the A105:01-B102:01/A105:01-B102:01 genotype and increased BMI was significant (Pandlt;0.006). The odds ratio in patients with this genotype of being obese was 1.80 (95% confidence interval 1.21-2.61; Pandlt;0.006). The increased proportion of overweight type 1 diabetes children with the A105:01-B102:01 haplotype was most pronounced in children diagnosed between 5 and 9 years of age. less thanbrgreater than less thanbrgreater thanConclusions: Susceptibility for childhood type 1 diabetes was unexpectedly found to be associated with the A105:01-B102:01/A105:01-B102:01 genotype and an increased BMI. These results support the hypothesis that overweight may contribute to the risk of type 1 diabetes in children positive for HLA-DQ A105:01-B102:01.
38.	Cerqueiro Bybrant, Mara, et al. (författare) High levels of anti-tissue transglutaminase antibodies predict biopsy proven celiac disease in children with type 1 diabetes 2019 Konferensbidrag (refereegranskat)
39.	Chia, Sean, et al. (författare) SAR by kinetics for drug discovery in protein misfolding diseases 2018 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 115:41, s. 10245-10250 Tidskriftsartikel (refereegranskat)abstract To develop effective therapeutic strategies for protein misfolding diseases, a promising route is to identify compounds that inhibit the formation of protein oligomers. To achieve this goal, we report a structure.activity relationship (SAR) approach based on chemical kinetics to estimate quantitatively how small molecules modify the reactive flux toward oligomers. We use this estimate to derive chemical rules in the case of the amyloid beta peptide (Aβ), which we then exploit to optimize starting compounds to curtail Aâ oligomer formation. We demonstrate this approach by converting an inactive rhodanine compound into an effective inhibitor of Aβ oligomer formation by generating chemical derivatives in a systematic manner. These results provide an initial demonstration of the potential of drug discovery strategies based on targeting directly the production of protein oligomers.
40.	Chowdary, Pratima, et al. (författare) Managing surgery in hemophilia with recombinant factor VIII Fc and factor IX Fc : Data on safety and effectiveness from phase 3 pivotal studies 2022 Ingår i: Research and Practice in Thrombosis and Haemostasis. - : Wiley. - 2475-0379. ; 6:5 Tidskriftsartikel (refereegranskat)abstract Background Surgical procedures impose hemostatic risk to people with hemophilia, which may be minimized by optimal factor (F) replacement therapy. Methods This analysis evaluates the efficacy and safety of extended half-life factor replacement recombinant FVIII and FIX Fc fusion proteins (rFVIIIFc and rFIXFc) during surgery in phase 3 pivotal (A-LONG/Kids A-LONG and B-LONG/Kids B-LONG) and extension (ASPIRE and B-YOND) studies. Dosing regimens were determined by investigators. Injection frequency, dosing, blood loss, transfusions, and hemostatic response were assessed. Results Forty-five major (n = 31 subjects) and 90 minor (n = 70 subjects) procedures were performed in hemophilia A; 35 major (n = 22) and 62 minor (n = 37) procedures were performed in hemophilia B. Unilateral knee arthroplasty was the most common major orthopedic procedure (hemophilia A: n = 15/34; hemophilia B: n = 8/24). On the day of surgery, median total dose in adults/adolescents was 81 IU/kg for rFVIIIFc and 144 IU/kg for rFIXFc; most major procedures required <= 2 injections (including loading dose). Through days 1-14, most major procedures had <= 1 injection/day. Hemostasis was rated excellent (rFVIIIFc: n = 39/42; rFIXFc: n = 29/33) or good (n = 3/42; n = 4/33) in evaluable major surgeries, with blood loss comparable with subjects without hemophilia. Most minor procedures in adults/adolescents required one injection on the day of surgery, including median loading dose of 51 IU/kg (rFVIIIFc) and 80 IU/kg (rFIXFc). No major treatment-related safety concerns were identified. No subjects developed inhibitors or serious vascular thromboembolic events. Conclusions rFVIIIFc and rFIXFc were efficacious and well tolerated for the management of perioperative hemostasis across a wide spectrum of major and minor surgeries in hemophilia.
41.	DAddio, Francesca, et al. (författare) The IGFBP3/TMEM219 pathway regulates beta cell homeostasis 2022 Ingår i: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1 Tidskriftsartikel (refereegranskat)abstract In this new study the Authors demonstrated that the IGFBP3/TMEM219 pathway is a physiological regulator of pancreatic beta cell homeostasis and it is dysregulated in diabetes. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes. Loss of pancreatic beta cells is a central feature of type 1 (T1D) and type 2 (T2D) diabetes, but a therapeutic strategy to preserve beta cell mass remains to be established. Here we show that the death receptor TMEM219 is expressed on pancreatic beta cells and that signaling through its ligand insulin-like growth factor binding protein 3 (IGFBP3) leads to beta cell loss and dysfunction. Increased peripheral IGFBP3 was observed in established and at-risk T1D/T2D patients and was confirmed in T1D/T2D preclinical models, suggesting that dysfunctional IGFBP3/TMEM219 signaling is associated with abnormalities in beta cells homeostasis. In vitro and in vivo short-term IGFBP3/TMEM219 inhibition and TMEM219 genetic ablation preserved beta cells and prevented/delayed diabetes onset, while long-term IGFBP3/TMEM219 blockade allowed for beta cell expansion. Interestingly, in several patients cohorts restoration of appropriate IGFBP3 levels was associated with improved beta cell function. The IGFBP3/TMEM219 pathway is thus shown to be a physiological regulator of beta cell homeostasis and is also demonstrated to be disrupted in T1D/T2D. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes.
42.	Delli, A J, et al. (författare) Clinical and genetical characterisation of a series of patients with type 1 diabetes induced by interferon therapy in DIABETOLOGIA, vol 53, issue , pp S119-S120 2010 Ingår i: DIABETOLOGIA. - : Springer Science Business Media. ; , s. S119-S120 Konferensbidrag (refereegranskat)abstract n/a
43.	Ekberg, Olle, et al. (författare) Investigating the presence of mold in wood treated with chlorophenol 2020 Ingår i: 12th Nordic Symposium on Building Physics (NSB 2020). - : EDP Sciences. - 2555-0403. ; 172 Konferensbidrag (refereegranskat)abstract A common moisture-related problem in Sweden and other countries, is mold odor indoors. The general perception is that mold odor indicates hazardous hidden mold. However, some grey literature studies indicate that the source of mold odor might not be substantial amounts of mold, but rather chloroanisoles (CAs) which are biomethylated from chlorophenols (CPs) in moist conditions. Products containing CPs were commonly used world-wide as wood preservatives in the 1960-70s and problems with indoor mold odor have been reported in buildings where such products have been used. In Sweden, one of the main uses of CPs in buildings was in wooden constructions exposed to big moisture loads, such as sill plates and crawl space ceilings. Here we aimed to determine the potential presence and level of mold growth on wood treated with CPs in one school building with reported odor problems built in the stated time period. Odorous wooden samples were taken and analyzed for mold growth. No mold was detected by the naked eye, but some growth was seen using a microscope. We presently investigate more schools and samples, but so far our results question that mold odor depends on substantial amounts of mold.
44.	Fakih, M., et al. (författare) SAFEPOWER project : Architecture for safe and power-efficient mixed-criticality systems 2017 Ingår i: Microprocessors and microsystems. - : Elsevier. - 0141-9331 .- 1872-9436. ; 52, s. 89-105 Tidskriftsartikel (refereegranskat)abstract With the ever increasing industrial demand for bigger, faster and more efficient systems, a growing number of cores is integrated on a single chip. Additionally, their performance is further maximized by simultaneously executing as many processes as possible without regarding their criticality. Even safety critical domains like railway and avionics apply these paradigms under strict certification regulations. As the number of cores is continuously expanding, the importance of cost-effectiveness grows. One way to increase the cost-efficiency of such System on Chip (SoC) is to enhance the way the SoC handles its power resources. By increasing the power efficiency, the reliability of the SoC is raised because the lifetime of the battery lengthens. Secondly, by having less energy consumed, the emitted heat is reduced in the SoC which translates into fewer cooling devices. Though energy efficiency has been thoroughly researched, there is no application of those power saving methods in safety critical domains yet. The EU project SAFEPOWER1.
45.	Fierabracci, A, et al. (författare) Osteopontin is an autoantigen of the somatostatin cells in human islets : identification by screening random peptide libraries with sera of patients with insulin-dependent diabetes mellitus. 1999 Ingår i: Vaccine. - 0264-410X .- 1873-2518. ; 18, s. 342-354 Tidskriftsartikel (refereegranskat)
46.	Gommenginger, Christine, et al. (författare) SEASTAR: A mission to study ocean submesoscale dynamics and small-scale atmosphere-ocean processes in coastal, shelf and polar seas 2019 Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6:JUL Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract High-resolution satellite images of ocean color and sea surface temperature reveal an abundance of ocean fronts, vortices and filaments at scales below 10 km but measurements of ocean surface dynamics at these scales are rare. There is increasing recognition of the role played by small scale ocean processes in ocean-atmosphere coupling, upper-ocean mixing and ocean vertical transports, with advanced numerical models and in situ observations highlighting fundamental changes in dynamics when scales reach 1 km. Numerous scientific publications highlight the global impact of small oceanic scales on marine ecosystems, operational forecasts and long-term climate projections through strong ageostrophic circulations, large vertical ocean velocities and mixed layer re-stratification. Small-scale processes particularly dominate in coastal, shelf and polar seas where they mediate important exchanges between land, ocean, atmosphere and the cryosphere e.g. freshwater, pollutants. As numerical models continue to evolve towards finer spatial resolution and increasingly complex coupled atmosphere-wave-ice-ocean systems, modern observing capability lags behind, unable to deliver the high-resolution synoptic measurements of total currents, wind vectors and waves needed to advance understanding, develop better parameterizations and improve model validations, forecasts and projections. SEASTAR is a satellite mission concept that proposes to directly address this critical observational gap with synoptic two-dimensional imaging of total ocean surface current vectors and wind vectors at 1 km resolution and coincident directional wave spectra. Based on major recent advances in squinted along-track Synthetic Aperture Radar interferometry, SEASTAR is an innovative, mature concept with unique demonstrated capabilities, seeking to proceed towards spaceborne implementation within Europe and beyond.
47.	Greenbaum, Carla, et al. (författare) Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes 2008 Ingår i: Diabetes Care. - 0149-5992 .- 1935-5548. ; 31:10, s. 1966-1971 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Beta-cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures. RESEARCH DESIGN AND METHODS: In randomized sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST tests on separate days, and 118 ECPT subjects completed 348 tests (up to 3 each) with either two MMTTs or two GSTs. RESULTS: Among individuals with up to 4 years' duration of type 1 diabetes, >85% had measurable stimulated C-peptide values. The MMTT stimulus produced significantly higher concentrations of C-peptide than the GST. Whereas both tests were highly reproducible, the MMTT was significantly more so (R(2) = 0.96 for peak C-peptide response). Overall, the majority of subjects preferred the MMTT, and there were few adverse events. Some older subjects preferred the shorter duration of the GST. Nausea was reported in the majority of GST studies, particularly in the young age-group. CONCLUSIONS: The MMTT is preferred for the assessment of beta-cell function in therapeutic trials in type 1 diabetes.
48.	Guo, Jian Ping, et al. (författare) Profound and paradoxical impact on arthritis and autoimmunity of the rat antigen-presenting lectin-like receptor complex 2008 Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 58:5, s. 1343-1353 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: The antigen-presenting lectin-like receptor complex (APLEC) was recently identified as a genetic determinant for arthritis susceptibility. We undertook this study to define mechanisms underlying the impact of APLEC on arthritis, to determine whether sex effects occur, and to determine whether APLEC influences different types of arthritis and phenotypes other than susceptibility. METHODS: Arthritis-susceptible DA rats were compared with sex-matched congenic rats in which APLEC alleles were substituted with alleles from arthritis-resistant PVG rats. Six different arthritogenic agents were injected at the base of the tail: Freund's incomplete adjuvant, pristane, squalene, killed mycobacteria, yeast beta-glucan, or rat type II collagen (CII). Arthritis was visually scored, body weight was measured, and anti-CII IgG and cytokine messenger RNA (mRNA) levels were determined by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction, respectively. RESULTS: In 5 models of rheumatoid arthritis (RA), congenic rats deviated profoundly from DA rats by having reduced arthritis susceptibility, delayed onset, decreased severity, and/or reduced body weight loss. Paradoxical opposite genetic effects were noted, including a more severe disease course in congenic males in pristane-induced arthritis and decreased clinical signs in collagen-induced arthritis despite increased autoantibody levels. Interestingly, the anti-CII IgG isotype profile was skewed in congenic rats, and markedly reduced lymph node mRNA levels for interleukin-17 suggested that the cytokine profile of autoreactive T helper cells was also skewed in a less pathogenic direction. CONCLUSION: Rat APLEC regulates autoimmunity and multiple phenotypes in several types of arthritis. However, delineating the genetic impact may require stratification for sex or mode of arthritis induction. This pathogenetic complexity should be considered when evaluating APLEC in inflammatory and autoimmune diseases, including RA.
49.	Gustafsson, Åsa, et al. (författare) Strain differences influence timing and magnitude of both acute and late inflammatory reactions after intratracheal instillation of an alkylating agent in rats 2014 Ingår i: Journal of Applied Toxicology. - : John Wiley & Sons. - 0260-437X .- 1099-1263. ; 34:3, s. 272-280 Tidskriftsartikel (refereegranskat)abstract The acute pulmonary responses after exposure to sulfur and nitrogen mustards are well documented whereas the late pulmonary effects are not. With a novel focus on the immune system this paper investigate whether late phase pulmonary effects developed in rats exposed to the nitrogen mustard melphalan are linked to the acute responses and whether the reactions are genetically regulated. The DA rat strain was used to establish a lung exposure model. Five other inbred rat strains (PVG, PVG.1AV1, LEW, WF and F344) were compared within the model at selected time points. All rat strains displayed a biphasic pattern of leukocyte infiltration in the lungs, dominated by neutrophils 2days after exposure and a second peak dominated by macrophages 29days after exposure. The number of macrophages was higher in the DA rat compared with the other strains. The infiltration of lymphocytes in the lungs varied in both time of appearance and magnitude between strains. The quantity of collagen deposition in the lungs varied between strains at day 90; LEW and WF displayed high collagen content which coincided with an increased level of cytotoxic T cells. LEW further displayed an increased number of T helper cells and natural killer (NK) T cells in the lungs. The results in this study suggest there is a link between the development of lung fibrosis and high cytotoxic cell responses and that there is a genetic influence, as there are variations in acute and late adverse reactions between rat strains in both timing and magnitude.Copyright (c) 2013 John Wiley & Sons, Ltd.
50.	Habchi, Johnny, et al. (författare) Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes 2018 Ingår i: Nature Chemistry. - : Springer Science and Business Media LLC. - 1755-4330 .- 1755-4349. ; 10:6, s. 673-683 Tidskriftsartikel (refereegranskat)abstract Alzheimer’s disease is a neurodegenerative disorder associated with the aberrant aggregation of the amyloid-β peptide. Although increasing evidence implicates cholesterol in the pathogenesis of Alzheimer’s disease, the detailed mechanistic link between this lipid molecule and the disease process remains to be fully established. To address this problem, we adopt a kinetics-based strategy that reveals a specific catalytic role of cholesterol in the aggregation of Aβ42 (the 42-residue form of the amyloid-β peptide). More specifically, we demonstrate that lipid membranes containing cholesterol promote Aβ42 aggregation by enhancing its primary nucleation rate by up to 20-fold through a heterogeneous nucleation pathway. We further show that this process occurs as a result of cooperativity in the interaction of multiple cholesterol molecules with Aβ42. These results identify a specific microscopic pathway by which cholesterol dramatically enhances the onset of Aβ42 aggregation, thereby helping rationalize the link between Alzheimer’s disease and the impairment of cholesterol homeostasis.

Skapa referenser, mejla, bekava och länka

Länka till träfflistan

Resultat 1-50 av 101

Avgränsa träffmängd

Typ av publikation: tidskriftsartikel (89); konferensbidrag (9); forskningsöversikt (2); doktorsavhandling (1)

Typ av innehåll: refereegranskat (99); övrigt vetenskapligt/konstnärligt (2)

Författare/redaktör: Ludvigsson, Johnny (48); Ludvigsson, Johnny, ... (19); Lernmark, Åke (18); Carlsson, Annelie (18); Marcus, C (14); Samuelsson, Ulf (12); visa fler...; Ivarsson, S A (10); Forsander, Gun, 1951 (9); Forsander, G (9); Lorentzen, Johnny C. (9); Johansson, C. (8); Marcus, Claude (8); Samuelsson, Ulf, 195 ... (8); Lindblad, B (7); Ivarsson, Sten (7); Geraghty, Daniel E. (7); Pyo, Chul-Woo (7); Nelson, Wyatt C. (7); Kockum, I. (6); Linse, Sara (6); Knowles, Tuomas P.J. (6); Vendruscolo, Michele (6); Casas, Rosaura (6); Chia, Sean (6); Habchi, Johnny (6); Zhao, Lue Ping (5); Larsson, Helena Eldi ... (5); Pozzilli, P. (5); Persson, Martina (5); Papadopoulos, George ... (5); Moustakas, Antonis K (5); Bondinas, George P (5); Dobson, Christopher ... (4); CARLSSON, A (4); Persson, M (4); Svensson, Jannet (4); Elding Larsson, Hele ... (4); Michaels, Thomas C T (4); Cohen, Samuel I A (4); Ortqvist, E (4); Pozzilli, Paolo (4); Cardwell, Chris R (4); Parslow, Roger C (4); Wadsworth, Emma J K (4); Brigis, Girts (4); Urbonaite, Brone (4); Schober, Edith (4); Devoti, Gabriele (4); Ionescu-Tirgoviste, ... (4); de Beaufort, Carine ... (4); visa färre...

Lärosäte: Linköpings universitet (66); Karolinska Institutet (39); Lunds universitet (33); Göteborgs universitet (16); Uppsala universitet (13); Umeå universitet (8); visa fler...; Örebro universitet (5); Kungliga Tekniska Högskolan (3); Högskolan i Gävle (3); Chalmers tekniska högskola (3); Sveriges Lantbruksuniversitet (2); Luleå tekniska universitet (1); Högskolan i Halmstad (1); Stockholms universitet (1); Jönköping University (1); visa färre...

Språk: Engelska (101)

Forskningsämne (UKÄ/SCB): Medicin och hälsovetenskap (55); Naturvetenskap (12); Teknik (6); Lantbruksvetenskap (1)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se

Stäng

Kopiera och spara länken för att återkomma till aktuell vy