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Sökning: WFRF:(Hägglund R.)

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  • Kluin-Nelemans, Hanneke C., et al. (författare)
  • Prognostic impact of eosinophils in mastocytosis : analysis of 2350 patients collected in the ECNM Registry
  • 2020
  • Ingår i: Leukemia. - : Nature Publishing Group. - 0887-6924 .- 1476-5551. ; 34:4, s. 1090-1101
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic mastocytosis (SM) is frequently associated with eosinophilia. To examine its prevalence and clinical impact in all WHO classification-based subcategories, we analyzed eosinophil counts in 2350 mastocytosis patients using the dataset of the European Competence Network on Mastocytosis. Ninety percent of patients had normal eosinophil counts, 6.8% mild eosinophilia (0.5-1.5x10(9)/l), and 3.1% hypereosinophilia (HE; >1.5x10(9)/l). Eosinophilia/HE were mainly present in patients with advanced SM (17%/19%), and only rarely recorded in patients with indolent and smoldering SM (5%/1%), and some patients with cutaneous mastocytosis. The eosinophil count correlated with organomegaly, dysmyelopoiesis, and the WHO classification, but not with mediator-related symptoms or allergy. Eosinophilia at diagnosis had a strong prognostic impact (p<0.0001) on overall survival (OS) and progression-free survival (PFS), with a 10-year OS of 19% for patients with HE, 70% for those with mild eosinophilia, and 88% for patients with normal eosinophil counts. In 89% of patients with follow-up data (n=1430, censored at start of cytoreductive therapy), eosinophils remained stable. In those with changing eosinophil counts (increase/decrease or mixed pattern), OS and PFS were inferior compared with patients with stable eosinophil counts. In conclusion, eosinophilia and HE are more prevalent in advanced SM and are predictors of a worse outcome.
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  • Lübke, Johannes, et al. (författare)
  • Serum chemistry profiling and prognostication in systemic mastocytosis : a registry-based study of the ECNM and GREM
  • 2024
  • Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 8:11, s. 2890-2900
  • Tidskriftsartikel (refereegranskat)abstract
    • Certain laboratory abnormalities correlate with subvariants of systemic mastocytosis (SM) and are often prognostically relevant. To assess the diagnostic and prognostic value of individual serum chemistry parameters in SM, 2607 patients enrolled within the European Competence Network on Mastocytosis and 575 patients enrolled within the German Registry on Eosinophils and Mast Cells were analyzed. For screening and diagnosis of SM, tryptase was identified as the most speci fic serum parameter. For differentiation between indolent and advanced SM (AdvSM), the following serum parameters were most relevant: tryptase, alkaline phosphatase, beta 2-microglobulin, lactate dehydrogenase (LDH), albumin, vitamin B12, and C-reactive protein (P < .001). With regard to subvariants of AdvSM, an elevated LDH of ≥ 260 U/L was associated with multilineage expansion (leukocytosis, r = 0.37, P < .001; monocytosis, r = 0.26, P < .001) and the presence of an associated myeloid neoplasm (P < .001), whereas tryptase levels were highest in mast cell leukemia (MCL) vs non-MCL (308 μg/L vs 146 μg/L, P = .003). Based on multivariable analysis, the hazard-risk weighted assignment of 1 point to LDH (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.1-4.0; P = .018) and 1.5 points each to β2-microglobulin (HR, 2.7; 95% CI, 1.4-5.4; P = .004) and albumin (HR, 3.3; 95% CI, 1.7-6.5; P = .001) delineated a highly predictive 3-tier risk classification system (0 points, 8.1 years vs 1 point, 2.5 years; ≥1.5 points, 1.7 years; P < .001). Moreover, serum chemistry parameters enabled further stratification of patients classified as having an International Prognostic Scoring System for Mastocytosis-AdvSM1/2 risk score (P = .027). In conclusion, serum chemistry pro filing is a crucial tool in the clinical practice supporting diagnosis and prognostication of SM and its subvariants.
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4.
  • Ademark, Pia, et al. (författare)
  • Cloning and characterisation of Aspergillus niger genes encoding an alpha-galactosidase and a beta-mannosidase involved in galactomannan degradation
  • 2001
  • Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956. ; 268:10, s. 2982-2990
  • Tidskriftsartikel (refereegranskat)abstract
    • α-Galactosidase (EC 3.2.1.22) and β-mannosidase (EC 3.2.1.25) participate in the hydrolysis of complex plant saccharides such as galacto(gluco)mannans. Here we report on the cloning and characterization of genes encoding an α-galactosidase (AglC) and a β-mannosidase (MndA) from Aspergillus niger. The aglC and mndA genes code for 747 and 931 amino acids, respectively, including the eukaryotic signal sequences. The predicted isoelectric points of AglC and MndA are 4.56 and 5.17, and the calculated molecular masses are 79.674 and 102.335 kDa, respectively. Both AglC and MndA contain several putative N-glycosylation sites. AglC was assigned to family 36 of the glycosyl hydrolases and MndA was assigned to family 2. The expression patterns of aglC and mndA and two other genes encoding A. nigerα-galactosidases (aglA and aglB) during cultivation on galactomannan were studied by Northern analysis. A comparison of gene expression on monosaccharides in the A. niger wild-type and a CreA mutant strain showed that the carbon catabolite repressor protein CreA has a strong influence on aglA, but not on aglB, aglC or mndA. AglC and MndA were purified from constructed overexpression strains of A. niger, and the combined action of these enzymes degraded a galactomanno-oligosaccharide into galactose and mannose. The possible roles of AglC and MndA in galactomannan hydrolysis is discussed.
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  • Ahlinder, J., et al. (författare)
  • Use of metagenomic microbial source tracking to investigate the source of a foodborne outbreak of cryptosporidiosis
  • 2022
  • Ingår i: FOOD AND WATERBORNE PARASITOLOGY. - : Elsevier. - 2405-6766. ; 26
  • Tidskriftsartikel (refereegranskat)abstract
    • Cryptosporidium is a protozoan parasite of global public health importance that causes gastroenteritis in a variety of vertebrate hosts, with many human outbreaks reported yearly, often from ingestion of contaminated water or food. Despite the major public health implications, little is typically known about sources of contamination of disease outbreaks caused by Cryptosporidium. Here, we study a national foodborne outbreak resulted from infection with Cryptosporidium parvum via romaine lettuce, with the main goal to trace the source of the parasite. To do so, we combined traditional outbreak investigation methods with molecular detection and characterization methods (i.e. PCR based typing, amplicon and shotgun sequencing) of romaine lettuce samples collected at the same farm from which the contaminated food was produced. Using 18S rRNA typing, we detected C. parvum in two out of three lettuce samples, which was supported by detections in the metagenome analysis. Microbial source tracking analysis of the lettuce samples suggested sewage water as a likely source of the contamination, albeit with some uncertainty. In addition, the high degree of overlap in bacterial species content with a public human gut microbial database corroborated the source tracking results. The combination of traditional and molecular based methods applied here is a promising tool for future source tracking investigations of food- and waterborne outbreaks of Cryptosporidium spp. and can help to control and mitigate contamination risks.
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7.
  • Andersen, Grethe, et al. (författare)
  • Quantitative measurement of the levels of melanocortin receptor subtype 1, 2, 3 and 5 and pro-opio-melanocortin peptide gene expression in subsets of human peripheral blood leucocytes
  • 2005
  • Ingår i: Scandinavian Journal of Immunology. - Oxford : Wiley. - 0300-9475 .- 1365-3083. ; 61:3, s. 279-284
  • Tidskriftsartikel (refereegranskat)abstract
    • Levels of the melanocortin receptor (MCR) 1, 2, 3 and 5 subtypes and pro-opio-melanocortin (POMC) protein mRNA were measured by the real-time quantitative reverse transcriptase polymerase chain reaction method in CD4+ T helper (Th) cells, CD8+ T cytotoxic cells, CD19+ B cells, CD56+ natural killer (NK) cells, CD14+ monocytes and CD15+ granulocytes from healthy donors. We found high levels of all of the MC1, 2, 3 and 5R subtype mRNA in Th cells and moderate levels in NK cells, monocytes and granulocytes. POMC peptide mRNA was found in all examined leucocyte subsets, but only low levels were present in granulocytes. Our findings suggest a co-ordinating role for MCR subtypes and their naturally occurring ligands in the co-operation between innate and adaptive immunity. Moreover, our findings are compatible with earlier finding of MCR-mediated tolerance induction in Th cells.
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  • Batchelor, W. J., et al. (författare)
  • Effect of test conditions on measured loads and displacements in zero and short span testing
  • 2003
  • Konferensbidrag (refereegranskat)abstract
    • Single fibre mechanical properties play a critical role in determining sheet mechanical properties, but these mechanical properties are rarely measured due to the time-consuming nature of the tests. The zero span strength is commonly used as a measure for the strength of the fibres, but the results also can depend on the test conditions. Modelling has shown that the load displacement curves are influenced by the thickness to span ratio, as there is an in-homogenous stress-field in the thickness direction of the sample. This paper will present data on the effect of grammage and clamping pressure on the loads and displacements in zero/short span tests. Clamps were designed and made for a displacement controlled load frame made by Material Testing System (MTS). These clamps can test up to ten plies of papers with a span length from 0 to 3 mm. For the sake of comparison, tests were made using a commercial zero/short span tester, which is load controlled but is limited in span length and thickness of the tested material. Both machines were found to give comparable results. Isotropic 65 gsm handsheets, 36 gsm aluminium foil and 42 gsm greaseproof paper (MD and CD) were tested as functions of clamping pressure and grammage. An intrinsic zero-span strength was defined as the y-axis intercept of plot. A recently published procedure for determining the short span stress-strain curve from zero and short span testing was evaluated for the effect of grammage, clamping pressure and span on the calculated result. It was concluded that the method only gives results that are independent of the test conditions when the conditions are carefully selected.
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