1. |
- Nilsson, Anna-Lena, et al.
(author)
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Relationship between Ljungan virus antibodies, HLA-DQ8, and insulin autoantibodies in newly diagnosed type 1 diabetes children
- 2013
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In: Viral immunology. - : Mary Ann Liebert, Inc.. - 0882-8245 .- 1557-8976. ; 26:3, s. 207-215
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Journal article (peer-reviewed)abstract
- Environmental factors, including viral infections, may explain an increasing and fluctuating incidence of childhood type 1 diabetes (T1D). Ljungan virus (LV) isolated from bank voles have been implicated, but it is unclear whether LV contributes to islet autoimmunity, progression to clinical onset, or both, of T1D. The aim was to test whether LV antibodies (LVAb) were related to HLA-DQ and islet autoantibodies in newly diagnosed T1D patients (n = 676) and controls (n = 309). Patients, 0-18 years of age, diagnosed with T1D in 1996-2005 were analyzed for LVAb, HLA-DQ genotypes, and all seven known islet autoantibodies (GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, and ZnT8QA). LVAb at 75th percentile, defined as cut off, was 90 (range 6-3936) U/mL and 4th quartile LVAb were found in 25% (170/676) of which 64% were < 10 (n = 108, p < 0.0001), and 27% were < 5 (n = 45; p < 0.0001) years old. The 4th quartile LVAb in children < 10 years of age correlated to HLA DQ2/8, 8/8, and 8/X (p < 0.0001). Furthermore, in the group with 4th quartile LVAb, 55% were IAA positive (p = 0.01) and correlation was found between 4th quartile LVAb and IAA in children < 10 years of age (p = 0.035). It is concluded that 1) LVAb were common among the young T1D patients and LVAb levels were higher in the younger age groups; 2) 4th quartile LVAb correlated with IAA; and 3) there was a correlation between 4th quartile LVAb and HLA-DQ8, particularly in the young patients. The presence of LVAb supports the notion that prior exposure to LV may be associated with T1D.
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2. |
- Carlsson, Annelie, et al.
(author)
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Prevalence of IgA-antigliadin antibodies and IgA-antiendomysium antibodies related to celiac disease in children with Down syndrome
- 1998
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In: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 101:2, s. 5-272
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Journal article (peer-reviewed)abstract
- OBJECTIVE: This study was undertaken to investigate the prevalence of celiac disease in children and adolescents with Down syndrome.MATERIAL AND METHODS: Forty-three children and adolescents with Down syndrome were screened for IgA-antigliadin antibodies (AGA) and IgA-antiendomysium antibodies (EMA). Patients found to be either AGA- or EMA-positive were investigated further with intestinal biopsy.RESULTS: None of the 43 patients had known celiac disease at entry into the study; 37% (16/43) were found to have AGA levels above normal, and 16% (7/43) to be EMA-positive. Of the 15 patients who underwent biopsy, 8 manifested villous atrophy. Villous atrophy was present in all 7 of the EMA-positive patients, whereas the villi were normal in 7 of the 13 AGA-positive patients who underwent biopsy.CONCLUSIONS: EMA is a good immunologic marker for use in screening for celiac disease, and screening is justified in patients with Down syndrome.
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4. |
- Carlsson, Anders, et al.
(author)
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Involvement of the Phospholipid Sterol Acyltransferase1 in Plant Sterol Homeostasis and Leaf Senescence
- 2010
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In: Plant Physiology. - : Oxford University Press (OUP). - 0032-0889 .- 1532-2548. ; 152, s. 107-119
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Journal article (peer-reviewed)abstract
- Genes encoding sterol ester-forming enzymes were recently identified in the Arabidopsis (Arabidopsis thaliana) genome. One belongs to a family of six members presenting homologies with the mammalian Lecithin Cholesterol Acyltransferases. The other one belongs to the superfamily of Membrane-Bound O-Acyltransferases. The physiological functions of these genes, Phospholipid Sterol Acyltransferase1 (PSAT1) and Acyl-CoA Sterol Acyltransferase1 (ASAT1), respectively, were investigated using Arabidopsis mutants. Sterol ester content decreased in leaves of all mutants and was strongly reduced in seeds from plants carrying a PSAT1-deficient mutation. The amount of sterol esters in flowers was very close to that of the wild type for all lines studied. This indicated further functional redundancy of sterol acylation in Arabidopsis. We performed feeding experiments in which we supplied sterol precursors to psat1-1, psat1-2, and asat1-1 mutants. This triggered the accumulation of sterol esters (stored in cytosolic lipid droplets) in the wild type and the asat1-1 lines but not in the psat1-1 and psat1-2 lines, indicating a major contribution of the PSAT1 in maintaining free sterol homeostasis in plant cell membranes. A clear biological effect associated with the lack of sterol ester formation in the psat1-1 and psat1-2 mutants was an early leaf senescence phenotype. Double mutants lacking PSAT1 and ASAT1 had identical phenotypes to psat1 mutants. The results presented here suggest that PSAT1 plays a role in lipid catabolism as part of the intracellular processes at play in the maintenance of leaf viability during developmental aging.
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5. |
- Carlsson, Anders, et al.
(author)
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Metabolic Interactions between the Lands Cycle and the Kennedy Pathway of Glycerolipid Synthesis in Arabidopsis Developing Seeds
- 2012
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In: Plant Cell. - : Oxford University Press (OUP). - 1040-4651 .- 1532-298X. ; 24, s. 4652-4669
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Journal article (peer-reviewed)abstract
- It has been widely accepted that the primary function of the Lands cycle is to provide a route for acyl remodeling to modify fatty acid (FA) composition of phospholipids derived from the Kennedy pathway. Lysophosphatidylcholine acyltransferase (LPCAT) is an evolutionarily conserved key enzyme in the Lands cycle. In this study, we provide direct evidence that the Arabidopsis thaliana LPCATs, LPCAT1 and LPCAT2, participate in the Lands cycle in developing seeds. In spite of a substantially reduced initial rate of nascent FA incorporation into phosphatidylcholine (PC), the PC level in the double mutant lpcat1 lpcat2-2 remained unchanged. LPCAT deficiency triggered a compensatory response of de novo PC synthesis and a concomitant acceleration of PC turnover that were attributable at least in part to PC deacylation. Acyl-CoA profile analysis revealed complicated metabolic alterations rather than merely reduced acyl group shuffling from PC in the mutant. Shifts in FA stereo-specific distribution in triacylglycerol of the mutant seed suggested a preferential retention of saturated acyl chains at the stereospecific numbering (sn)-1 position from PC and likely a channeling of lysophosphatidic acid, derived from PC, into the Kennedy pathway. Our study thus illustrates an intricate relationship between the Lands cycle and the Kennedy pathway.
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6. |
- Carlsson, Annelie, et al.
(author)
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Prevalence of IgA-antiendomysium and IgA-antigliadin autoantibodies at diagnosis of insulin-dependent diabetes mellitus in Swedish children and adolescents
- 1999
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In: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 103:6 I, s. 1248-1252
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Journal article (peer-reviewed)abstract
- Objective. This study was conducted to investigate the prevalence of celiac disease (CD) in children and adolescents at diagnosis of insulin- dependent diabetes mellitus (IDDM) before insulin treatment was started. Material and Methods. At diagnosis of IDDM, and before treatment was started, 115 children and adolescents were screened for IgA-antiendomysium (EMA) and IgA-antigliadin antibodies (AGA). Those found to be EMA-positive and/or AGA- positive were investigated further with intestinal biopsy. Results. Of the 115 patients, 2 had known CD at diagnosis of IDDM; of the remainder of patients, 6% (7/113) were found to be EMA-positive and 9% (10/113) were found to have AGA levels above normal. Of the 6 patients who underwent biopsy, 5 manifested villous atrophy. In addition, 2 patients with high EMA and AGA antibody titers refused biopsy, and 4 patients with low EMA and/or AGA titers were found to have normal titers at control before biopsy decision. Conclusion. Because the prevalence of CD at diagnosis of IDDM would seem to be 6% to 8%, screening for CD seems to be justified among patients with newly diagnosed IDDM.
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7. |
- Carlsson, Anders, et al.
(author)
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Replacing fossil oil with fresh oil - with what and for what?
- 2011
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In: European Journal of Lipid Science and Technology. - : Wiley. - 1438-7697 .- 1438-9312. ; 113, s. 812-831
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Research review (peer-reviewed)abstract
- Industrial chemicals and materials are currently derived mainly from fossil-based raw materials, which are declining in availability, increasing in price and are a major source of undesirable greenhouse gas emissions. Plant oils have the potential to provide functionally equivalent, renewable and environmentally friendly replacements for these finite fossil-based raw materials, provided that their composition can be matched to end-use requirements, and that they can be produced on sufficient scale to meet current and growing industrial demands. Replacement of 40% of the fossil oil used in the chemical industry with renewable plant oils, whilst ensuring that growing demand for food oils is also met, will require a trebling of global plant oil production from current levels of around 139 MT to over 400 MT annually. Realisation of this potential will rely on application of plant biotechnology to (i) tailor plant oils to have high purity (preferably > 90%) of single desirable fatty acids, (ii) introduce unusual fatty acids that have specialty end-use functionalities and (iii) increase plant oil production capacity by increased oil content in current oil crops, and conversion of other high biomass crops into oil accumulating crops. This review outlines recent progress and future challenges in each of these areas.Practical applications: The research reviewed in this paper aims to develop metabolic engineering technologies to radically increase the yield and alter the fatty acid composition of plant oils and enable the development of new and more productive oil crops that can serve as renewable sources of industrial feedstocks currently provided by non-renewable and polluting fossil-based resources. As a result of recent and anticipated research developments we can expect to see significant enhancements in quality and productivity of oil crops over the coming decades. This should generate the technologies needed to support increasing plant oil production into the future, hopefully of sufficient magnitude to provide a major supply of renewable plant oils for the industrial economy without encroaching on the higher priority demand for food oils. Achievement of this goal will make a significant contribution to moving to a sustainable carbon-neutral industrial society with lower emissions of carbon dioxide to the atmosphere and reduced environmental impact as a result.
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8. |
- Carlsson, Lena, et al.
(author)
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Mode of growth determines differential expression of prostasomes in cultures of prostate cancer cell lines and opens for studies of prostasome gene expression
- 2006
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In: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 111:3, s. 293-301
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Journal article (peer-reviewed)abstract
- The exocrine secretion of the acinar gland cells in the human prostate consists of, among other components, a serous secretion and prostasomes. The prostasomes are functionally associated with both reproduction and prostate cancer development and are capable to raise autoantibodies at various pathologies. Therefore, we are trying to characterize prostasome antigens by analysing prostasome- producing cell lines of prostate cancers with the cDNA microarray technique. To obtain one state with synthesis of prostasomes and another state without synthesis, we checked whether the prostasome differentiation was influenced by the mode of growing the cells, that is, whether the cells had been growing on a solid support or on a flexible one. We studied the expression of prostasomes in the cell lines PC3, DU145 and LNCaP. We grew the cells with the following methods: Monocellular layers on microbeads, multicellular spheroids, single cells in suspension cultures, and xenotransplants in nude rats. The presence of prostasomes was examined by ELISA, immunocytochemistry or electron microscopy. The results showed that growing the cells on microbeads (solid support) produced a differentiation of prostasomes, while growing the cells in multicellular spheroids (flexible support) did not. Thus it should be possible to apply cDNA microarray analyses for characterizing the genes which are active at the cellular expression of prostasomes and then deduce the prostasome antigens.
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9. |
- Carlsson, Markus, et al.
(author)
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Inflammatory and circulatory effects of the reduction of endotoxin concentration in established porcine endotoxemic shock : a model of endotoxin elimination
- 2009
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In: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 37:3, s. 1031-e4
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Journal article (peer-reviewed)abstract
- Objective:To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction.Design:Prospective parallel-grouped placebo-controlled randomized interventional experimental study.Setting:University research unit.Subjects: Healthy pigs.Interventions:The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 µg endotoxin × kg-1 × h-1 for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively.Measurements and Main Results:During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-[alpha] (TNF-[alpha]) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-[alpha] concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao2, Paco2, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage.Conclusions:Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-[alpha] peak or later will have very little or no effect on TNF-[alpha]–mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.
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10. |
- Doan, Thuy, et al.
(author)
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Biochemical characteristics of AtFAR2, a fatty acid reductase from Arabidopsis thaliana that reduces fatty acyl-CoA and -ACP substrates into fatty alcohols
- 2016
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In: Acta Biochimica Polonica. - : Polskie Towarzystwo Biochemiczne (Polish Biochemical Society). - 0001-527X .- 1734-154X. ; 63, s. 565-570
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Journal article (peer-reviewed)abstract
- Fatty alcohols and derivatives are important for proper deposition of a functional pollen wall. Mutations in specific genes encoding fatty acid reductases (FAR) responsible for fatty alcohol production cause abnormal development of pollen. A disrupted AtFAR2 (MS2) gene in Arabidopsis thaliana results in pollen developing an abnormal exine layer and a reduced fertility phenotype. AtFAR2 has been shown to be targeted to chloroplasts and in a purified form to be specific for acyl-ACP substrates. Here, we present data on the in vitro and in planta characterizations of AtFAR2 from A. thaliana and show that this enzyme has the ability to use both, C16:0-ACPand C16:0-CoA, as substrates to produce C16:0-alcohol. Our results further show that AtFAR2 is highly similar in properties and substrate specificity to AtFAR6 for which in vitro data has been published, and which is also a chloroplast localized enzyme. This suggests that although AtFAR2 is the major enzyme responsible for exine layer functionality, AtFAR6 might provide functional redundancy to AtFAR2.
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