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61.
Raija Uusitalo-Sepp?l? Reetta Huttunen Janne Aittoniemi Pertti Koskinen Aila Leino Tero Vahlberg Esa M. Rintala 《PloS one》2013,8(1)
Background
Early diagnostic and prognostic stratification of patients with suspected infection is a difficult clinical challenge. We studied plasma pentraxin 3 (PTX3) upon admission to the emergency department in patients with suspected infection.Methods
The study comprised 537 emergency room patients with suspected infection: 59 with no systemic inflammatory response syndrome (SIRS) and without bacterial infection (group 1), 67 with bacterial infection without SIRS (group 2), 54 with SIRS without bacterial infection (group 3), 308 with sepsis (SIRS and bacterial infection) without organ failure (group 4) and 49 with severe sepsis (group 5). Plasma PTX3 was measured on admission using a commercial solid-phase enzyme-linked immunosorbent assay (ELISA).Results
The median PTX3 levels in groups 1–5 were 2.6 ng/ml, 4.4 ng/ml, 5.0 ng/ml, 6.1 ng/ml and 16.7 ng/ml, respectively (p<0.001). The median PTX3 concentration was higher in severe sepsis patients compared to others (16.7 vs. 4.9 ng/ml, p<0.001) and in non-survivors (day 28 case fatality) compared to survivors (14.1 vs. 5.1 ng/ml, p<0.001). A high PTX3 level predicted the need for ICU stay (p<0.001) and hypotension (p<0.001). AUCROC in the prediction of severe sepsis was 0.73 (95% CI 0.66–0.81, p<0.001) and 0.69 in case fatality (95% CI 0.58–0.79, p<0.001). PTX3 at a cut-off level for 14.1 ng/ml (optimal cut-off value for severe sepsis) showed 63% sensitivity and 80% specificity. At a cut-off level 7.7 ng/ml (optimal cut-off value for case fatality) showed 70% sensitivity and 63% specificity in predicting case fatality on day 28.In multivariate models, high PTX3 remained an independent predictor of severe sepsis and case fatality after adjusting for potential confounders.Conclusions
A high PTX3 level on hospital admission predicts severe sepsis and case fatality in patients with suspected infection. 相似文献62.
Helena Tossavainen Satu H. Helppolainen Juha A. E. Määttä Tero Pihlajamaa Vesa P. Hytönen Markku S. Kulomaa Perttu Permi 《Biomolecular NMR assignments》2013,7(1):35-38
Avidin is a homotetrameric ~56 kDa protein found in chicken egg white. Avidin’s ability to bind biotin with a very high affinity has widely been exploited in biotechnological applications. Protein engineering has further diversified avidin’s feasibility. ChiAVD(I117Y) is a product of rational protein engineering. It is a hyperthermostable synthetic hybrid of avidin and avidin-related protein 4 (AVR4). In this chimeric protein a 23-residue segment in avidin has been replaced with the corresponding sequence found in AVR4, and a point mutation at subunit interface 1–3 (and 2–4) has been introduced. Here we report the backbone and sidechain resonance assignments of the biotin-bound form of ChiAVD(I117Y) as well as the backbone resonance assignments of the free form. 相似文献
63.
Mikko Taina Ritva Vanninen Marja Hedman Pekka J?k?l? Satu K?rkk?inen Tero Tapiola Petri Sipola 《PloS one》2013,8(11)
Background
Ischemic strokes without a well-defined etiology are labeled as cryptogenic, and account for 30–40% of strokes in stroke registries. The left atrial appendage (LAA) is the most typical origin for intracardiac thrombus formation when associated with atrial fibrillation. Here, we examined whether increased LAA volume detected with cardiac computed tomography (cCT) constitutes a risk factor in cryptogenic stroke patients.Methods
This study included 82 stroke/TIA patients (57 males; mean age, 58 years) with a diagnosis of cryptogenic stroke after extensive radiological and cardiological investigations. Cases were classified using the TOAST criteria modified by European Association of Echocardiography recommendations for defining cardiac sources of embolism. Forty age- and gender-matched control subjects without cardiovascular diseases were selected for pair-wise comparisons (21 males; mean age, 54 years). LAA volume adjusted for body surface area was measured three dimensionally by tracing the LAA borders on electrocardiogram-gated CT slices.Results
In control subjects, mean LAA volume was 3.4±1.1 mL/m2. Mean+2SD, which was considered the upper limit for normal LAA volume was 5.6 mL/m2. In paired Student t-test between the patient group and matched controls, LAA volume was 67% larger in cryptogenic stroke/TIA patients (5.7±2.0 mL/m2 vs. 3.4±1.1 mL/m2; P<0.001). Forty-five (55%) patients with cryptogenic stroke/TIA had enlarged LAA.Conclusion
LAA is significantly enlarged in more than half of patients with cryptogenic stroke/TIA. LAA thrombosis may contribute to the pathogenesis of stroke in patients considered to have cryptogenic stroke after conventional evaluation. 相似文献64.
Pauliina Repo Johannes E. Jntti Reetta‐Stiina Jrvinen Elina S. Rantala Martin Tll Virpi Raivio Tero T. Kivel Joni A. Turunen 《Pigment cell & melanoma research》2020,33(5):756-762
Uveal melanoma (UM) is a rare intraocular cancer with the highest incidence in northern latitudes. Metastases develop in approximately 50% of patients, whereafter the median survival is 13 months. Generally, the mutation burden of these tumors is low. Germline variants predisposing to UM have been previously described in BRCA1‐associated protein 1 (BAP1). Recently, germline and somatic loss‐of‐function (LOF) variants in the methyl‐CpG‐binding domain 4 (MBD4) gene have been found to cause a hypermutated UM, and MBD4 also has been put forward as a gene predisposing to UM. We sequenced for MBD4 germline variants in 440 Finnish patients with UM and identified seven rare exonic missense variants in 16 (3.6%) patients, of which one likely alters MBD4 function. The frequency of likely pathogenic variants in our cohort is 0.23% (1/432; 95% CI, 0.01–1.28). We identified no LOF variants though their frequency in the Finnish population is 0.052%. Thus, our data do not support the suggestion that MBD4 germline variants predispose to UM. Somatic loss of MBD4 might modify the mutational burden in UM and change its response to immune checkpoint inhibitors. 相似文献
65.
66.
Natunen S Satomaa T Pitkänen V Salo H Mikkola M Natunen J Otonkoski T Valmu L 《Glycobiology》2011,21(9):1125-1130
The expression of the epitopes recognized by the monoclonal antibodies Tra-1-60 and Tra-1-81 is routinely used to assess the pluripotency status of human embryonic stem cells (hESCs) and induced pluripotent stem (iPS) cells. Although it is known that the epitopes recognized by Tra-1-60 and Tra-1-81 are carbohydrates, the exact molecular identity of these epitopes has been unclear. Glycan array analysis with more than 500 oligosaccharide structures revealed specific binding of Tra-1-60 and Tra-1-81 to two molecules containing terminal type 1 lactosamine: Galβ1-3GlcNAcβ1-3Galβ1-4GlcNAc and Galβ1-3GlcNAcβ1-3Galβ1-4GlcNAcβ1-6(Galβ1-3GlcNAcβ1-3)Galβ1-4Glc. The type 1 disaccharide in itself was not sufficient for binding, indicating that the complete epitope requires an extended tetrasaccharide structure where the type 1 disaccharide is β1,3-linked to type 2 lactosamine. Our mass spectrometric analysis complemented with glycosidase digestions of hESC O-glycans indicated the presence of the extended tetrasaccharide epitope on an O-glycan with the likely structure Galβ1-3GlcNAcβ1-3Galβ1-4GlcNAcβ1-6(Galβ1-3)GalNAc. Thus, the present data indicate that the pluripotency marker antibodies Tra-1-60 and Tra-1-81 recognize the minimal epitope Galβ1-3GlcNAcβ1-3Galβ1-4GlcNAc, which is present in hESCs as a part of a mucin-type O-glycan structure. The exact molecular identity of Tra-1-60 and Tra-1-81 is important for the development of improved tools to characterize the pluripotent phenotype. 相似文献
67.
Leppänen VM Tossavainen H Permi P Lehtiö L Rönnholm G Goldman A Kilpelaïnen I Pihlajamaa T 《The Journal of biological chemistry》2007,282(32):23219-23230
Collagen IX, located on the surface of collagen fibrils, is crucial for cartilage integrity and stability. The N-terminal NC4 domain of the alpha1(IX) chain is probably important in this because it interacts with various macromolecules such as proteoglycans and cartilage oligomeric matrix protein. At least 17 distinct collagen polypeptides carry an NC4-like unit near their N terminus, but this report, describing the crystal structure of NC4 at 1.8-A resolution, represents the first atomic level structure for these domains. The structure is similar to previously characterized laminin-neurexin-sex hormone binding globulin (LNS) structures, dominated by an antiparallel beta-sheet sandwich. In addition, a zinc ion was found in a position similar to that of the metal binding site of other LNS domains. A partial backbone NMR assignment of NC4 was obtained and utilized in NMR titration studies to investigate the zinc binding in solution state and to quantitate the affinity of metal binding. The K(d) of 11.5 mM suggests a regulatory rather than a structural role for zinc in solution. NMR titration with a heparin tetrasaccharide revealed the presence of a secondary binding site for heparin on NC4, showing structural and functional conservation with thrombospondin-1, but a markedly reduced affinity for the ligand. Also the overall arrangement of the N and C termini of NC4 resembles most closely the N-terminal domain of thrombospondin-1, distinguishing the two from the majority of the published LNS structures. 相似文献
68.
The young successional stages of boreal forests are an important habitat for many saproxylic species. These habitats are formed
by disturbances such as forest fires and they are characterized by large volumes of dead wood and sun-exposed conditions.
Today, young successional stages of natural origin are very rare in Fennoscandia and there is need for restoration. We constructed
a large-scale field experiment in which we studied the effects of two restoration practices on beetle diversity: controlled
burning and partial harvesting with creating different volumes of dead wood. We sampled beetles with flight-intercept traps
recording a total of 56,031 individuals and 755 species. The species richness and abundance of both saproxylic and non-saproxylic
beetles were increased by burning and harvesting but the volume of dead wood created on harvested sites had no short-term
effect on species richness or abundance. Rare species, especially saproxylic ones, preferred burned sites and a similar trend
was observed among red-listed and pyrophilous species. Burning and harvesting also resulted in different species assemblages
and there were some additional differences according to the volume of dead wood. We conclude that fire can be successfully
used in restoration of managed boreal forests to increase species diversity and to facilitate the recovery of declined species.
However, long-term monitoring is needed to clarify the effects of the restoration practices, in particular those of creating
dead wood without using fire. 相似文献
69.
Appelblom H Nurmi J Soukka T Pasternack M Penttilä KE Lövgren T Niemelä P 《Journal of biomolecular screening》2007,12(6):842-848
A homogeneous high-throughput screening method based on time-resolved fluorescence resonance energy transfer (TR-FRET) for the measurement of calcium-dependent multimerization of an EF-hand protein, sorcin, is described. The assay is based on a specific sorcin binding peptide conjugated either with an intrinsically highly fluorescent europium chelate (donor) or an Alexa Fluor 700 fluorophore (acceptor). Addition of calcium results in multimerization of sorcin, allowing several peptides to bind simultaneously to the epitopes of the multimeric protein complex, and the proximity of peptides labeled either with donor or acceptor label results in fluorescence resonance energy transfer between the 2 labels. When no calcium is present, the protein remains in a monomer form, and thus no FRET can take place. In the optimized assay construct, the assay was performed in 45 min, and a more than 20-fold signal-to-background ratio was achieved. The reversibility of sorcin multimerization was shown by chelating free calcium with ethylenediamine tetraacetic acid (EDTA). The developed homogeneous assay can be used in screening molecules that either inhibit or enhance multimerization of sorcin, and the assay format is applicable to various noncompetitive high-throughput screening assays detecting protein multimerization reactions. 相似文献
70.
Fischer Mibu Maxwell Kimberley Nuunoq Pedersen Halfdan Greeno Dean Jingwas Nang Graham Blair Jamie Hugu Sutej Mustonen Tero Murtomäki Eero Mustonen Kaisu 《Reviews in Fish Biology and Fisheries》2022,32(1):271-296
Reviews in Fish Biology and Fisheries - Coastal Indigenous and Traditional communities are starting to see changes to their lives from climate change, whether this is from species range changes or... 相似文献