| 861. |
- Jonsson, M, et al.
(författare)
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Plasmaproteiner, inflammation och amyloidos
- 2018. - 10
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Ingår i: Laurells klinisk kemi i praktisk medicin.. - Lund : Studentlitteratur AB. - 9789144119748 ; , s. 87-130
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Bokkapitel (refereegranskat)
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| 862. |
- Jung Lee, Eun Jung, et al.
(författare)
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Analysis of expression profiling data suggests explanation for difficulties in finding biomarkers for nasal polyps
- 2020
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Ingår i: Rhinology. - : INT RHINOLOGIC SOC. - 0300-0729 .- 1996-8604. ; 58:4, s. 360-367
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Tidskriftsartikel (refereegranskat)abstract
- Background: Identification of clinically useful biomarkers for Nasal Polyposis in chronic rhinosinusitis (CRSwNP) has proven difficult. We analyzed gene expression profiling data to find explanations for this. Methods:We analyzed mRNA expression profiling data, GSE36830, of six uncinate tissues from healthy controls and six NP from CRSwNP patients. We performed Ingenuity Pathway Analysis (IPA) of differentially expressed genes to identify pathways and predicted upstream regulators. Results: We identified 1,608 differentially expressed genes and 177 significant pathways, of which Th1 and Th2 activation pathway and leukocyte extravasation signaling were most significant. We identified 75 upstream regulators whose activity was predicted to be upregulated.These included regulators of known pathogenic and therapeutic relevance, like IL-4. However, only seven of the 75 regulators were actually differentially expressed in NP, namely CSF1, TYROBP, CCL2, CCL11, SELP, ADORA3, ICAM1. Interestingly, these did not include IL-4, and four of the seven were receptors. This suggested a potential explanation for the discrepancy between the predicted and observed expression levels of the regulators, namely that the receptors, and not their ligands, were upregulated. Indeed, we found that 10 receptors of key predicted upstream regulators were upregulated, including IL4R. Conclusion: Our findings indicate that the difficulties in finding specific biomarkers for CRSwNP depend on the complex underlying mechanisms, which include multiple pathways and regulators, each of which may be subdivided into multiple components such as ligands, soluble and membrane-bound receptors. This suggests that combinations of biomarkers may be needed for CRSwNP diagnostics.
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| 863. |
- Järemo, Petter, et al.
(författare)
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Platelets, gender and acute cerebral infarction
- 2015
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Ingår i: Journal of Translational Medicine. - : BioMed Central. - 1479-5876 .- 1479-5876. ; 13:267
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivePlatelets may well be significant in the pathogenesis of cerebral infarction. Platelets vary substantially according to gender. The scope of our current work is to establish if female and male stroke sufferers differ regarding platelet reactivity.Patients and methods73 Consecutive individuals stricken by acute ischemic cerebral infarction (31 females, 42 males) participated. All stroke subtypes were included. Platelet counts was determined electronically. Platelet reactivity i.e. the presence of surface-bound fibrinogen following provocation was analyzed with a flow cytometer. ADP (1.7 μmol/L) and a thrombin receptor agonist (TRAP-6) (57 μmol/L) were the agonists used.ResultsFemale stroke sufferers had higher platelet counts (p = 0.013) but their platelets were less reactive. The p values were (p = 0.038) and (p = 0.016) for ADP and TRAP-6, respectively.ConclusionThe current study demonstrates that women suffering acute cerebral infarction have less reactive platelets. It is concluded that gender affects platelets. Our study indicates that it may be beneficial to individualize platelet inhibition of stroke sufferers according to gender.
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| 864. |
- Järås, Kerstin, et al.
(författare)
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Porous silicon antibody microarrays for quantitative analysis: Measurement of free and total PSA in clinical plasma samples.
- 2012
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Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981.
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Tidskriftsartikel (refereegranskat)abstract
- The antibody microarrays have become widespread, but their use for quantitative analyses in clinical samples has not yet been established. We investigated an immunoassay based on nanoporous silicon antibody microarrays for quantification of total prostate-specific-antigen (PSA) in 80 clinical plasma samples, and provide quantitative data from a duplex microarray assay that simultaneously quantifies free and total PSA in plasma. To further develop the assay the porous silicon chips was placed into a standard 96-well microtiter plate for higher throughput analysis. The samples analyzed by this quantitative microarray were 80 plasma samples obtained from men undergoing clinical PSA testing (dynamic range: 0.14-44ng/ml, LOD: 0.14ng/ml). The second dataset, measuring free PSA (dynamic range: 0.40-74.9ng/ml, LOD: 0.47ng/ml) and total PSA (dynamic range: 0.87-295ng/ml, LOD: 0.76ng/ml), was also obtained from the clinical routine. The reference for the quantification was a commercially available assay, the ProStatus PSA Free/Total DELFIA. In an analysis of 80 plasma samples the microarray platform performs well across the range of total PSA levels. This assay might have the potential to substitute for the large-scale microtiter plate format in diagnostic applications. The duplex assay paves the way for a future quantitative multiplex assay, which analyzes several prostate cancer biomarkers simultaneously.
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| 865. |
- Jönsson, Anneli, et al.
(författare)
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Causes of nephrotic syndrome in Sweden: The relevance of clinical presentation and demographics
- 2023
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Ingår i: Frontiers in Nephrology. - : Frontiers Media SA. - 2813-0626. ; 3, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many pathological processes can disrupt the integrity of the glomerular capillary wall and cause a massive leakage of protein, resulting in nephrotic syndrome (NS). Clinical parameters such as age, sex, renal function, presence of diabetes, and how NS is defined influence the spectrum of underlying diseases. In this study, we examine how these parameters interact.Methods: Age, sex, hematuria, proteinuria, plasma creatinine plasma albumin levels, and final diagnosis were retrieved for all adult patients with NS as an indication for biopsy and/or massive albuminuria in conjunction with low plasma albumin from the biopsy module of the Swedish Renal Registry (SRR) between 2014 and 2019. A basic calculator was developed to demonstrate the importance of clinical presentation in relation to the likelihood of having a specific diagnosis.Results: A total of 913 unique patients were included in the study. Diabetic nephropathy (DN) and membranous nephropathy (MN) (both found in 17% of patients) were the most common diagnoses. With a stringent definition of NS, MN and minimal change nephropathy (MCN) increased in proportion. Among the cohort as a whole, MCN was the most frequent diagnosis in women and those < 50 years of age (found in 21% and 17%, respectively). In the case of patients aged between 50 and 70 years, those with chronic kidney disease stage 4, and those with negative dipstick tests for hematuria, the most common underlying disease was DN (in 23%, 30%, and 21% of cases, respectively). Among those with high-grade hematuria (dipstick grade 3 or 4), membranoproliferative glomerulonephritis was the most common diagnosis (14%), closely followed by IgA nephropathy (13%). Focal segmental glomerulosclerosis (9.7%) was less common than in many comparable studies.Conclusion: Clinical parameters have a profound impact on the likelihood of different diagnoses in adult patients with NS. Differences in clinical practice and study inclusion criteria may be more important than genetic background and environmental factors when explaining differences between studies in different parts of the world
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| 866. |
- Jönsson, Bodil, 1959, et al.
(författare)
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Phagocytosis and cytokine response to rough and smooth colony variants of Mycobacterium abscessus by human peripheral blood mononuclear cells.
- 2013
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463. ; 121:1, s. 45-55
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Tidskriftsartikel (refereegranskat)abstract
- Mycobacterium abscessus is a non-tuberculous mycobacteria able to cause opportunistic infections in selected patient groups. During the last decades it has emerged as a cause of chronic pulmonary infection in patients with cystic fibrosis (CF). M. abscessus strains exhibit either smooth or rough colony morphology. Strains exhibiting the rough phenotype more often cause pulmonary infections in CF patients than did the smooth ones. Here, we examined phagocytosis and production of cytokines by human peripheral blood mononuclear cells, in response to M. abscessus strains with smooth and rough colony phenotype. The rough isolates all formed multicellular cords, similar to what is observed in Mycobacterium tuberculosis. Monocytes were generally unable to internalize these rough cord isolates, in contrast with the smooth ones. Furthermore, the rough M. abscessus strains induced a distinct cytokine profile differing from that induced by the smooth ones. Rough isolates induced significantly less IL-10 and tumour necrosis factor compared to smooth strains, but more IL-1β. Both varieties induced equal amounts of IFN-γ, IL-17, IL-23, IL-6, IL-8 and equally little IL-12. The ability to withstand phagocytosis might be a virulence factor contributing to the capacity of rough M. abscessus strains to give persistent pulmonary infections.
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| 867. |
- Jöud, Magnus
(författare)
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Bioinformatic studies of genetic variation at known, novel and candidate blood group loci
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Access to compatible blood for transfusion is a prerequisite for modern health care. The compatibility is limited by the presence of antibodies to blood group antigens, polymorphic protein and carbohydrate structures, on the surface of the red blood cell. Blood group antigens arise from genetic variation in the genes underlying their expression. Knowledge of these genes and their variation can facilitate the provision of compatible blood.The overall aim of the thesis, comprising four papers, was to study the genetic variation at loci underlying human blood group systems and antigens, using bioinformatic methods. In Paper I, the genetic background of the Vel– blood group phenotype was elucidated. In Paper II, the genetic variants regulating the variable expression of the Vel blood group antigen was studied. In Paper III, whole genome sequencing (WGS) data from the 1000 Genomes project were used to create a database of all alleles in known blood group-related genes and to predict the presence of novel blood group antigens. Finally, in Paper IV, human glycosyltransferase genes expressed in erythroid tissue were identified and the potential for candidate carbohydrate-based blood group systems was predicted.Using SNP array data from Vel-phenotyped blood donors, including members of two families, a 17-base-pair deletion in the previously uncharacterized but evolutionary conserved gene SMIM1 was found to cause the Vel− bloodgroup phenotype. In Vel+ blood donors from different populations, two polymorphisms in intron 1 of SMIM1, rs1175550, and, to a lesser extent, rs143702418, were found to affect the expression of the Vel blood group antigen. In WGS data from the 1000 Genomes project, a large number of previously unreported blood group gene-related alleles were found and compiled into a database, Erythrogene. Among all identified genetic variants, 357 were non-synonymous and predicted to occur on the extracellular portion of blood group-carrying proteins and may represent novel or modified blood group antigens. In the human genome, 244 expressed glycosyltransferase genes were identified, 30 of which were predicted to have properties similar to known genes in carbohydrate-based blood group systems.The use of bioinformatic methods in the search of genetic variation underlying blood group systems and antigens was successful. The benefits of utilizing publicly available genotyping data in studies of blood groups are highlighted.
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| 868. |
- Kaden, Rene, 1975-, et al.
(författare)
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Brucella abortus : determination of survival times and evaluation of methods for detection in several matrices
- 2018
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Brucella abortus is a highly pathogenic zoonotic agent, tempting for the development of a rapid diagnostic method to enable adequate treatment and prevent further spread. Enrichment of the bacteria is often used as a first step in diagnostics to increase the bacterial number above the detection limit of the real-time PCR. The enrichment of Brucella spp. takes at least 3 days, which might be avoidable if sensitive PCR methods can be used. Since many matrices contain PCR inhibitors, the limit of detection (LOD) must be determined for each separate matrix. Another aim of this study was the determination of survival of Brucella abortus in the analyzed matrices. METHODS: The LOD for the detection of B. abortus in 14 matrices, relevant for human medicine, veterinary medicine and food and feed safety, was determined to evaluate the need of a pre-enrichment step prior to real-time PCR. The survival of B. abortus in the spiked matrices was tested by plate count in a 7-day interval for 132 days. RESULTS: The limit of detection for B. abortus in most matrices was in the range of 10(3)-10(4) CFU/g for cultivation and 10(4)-10(5) CFU/g for direct real-time PCR. The survival time of B. abortus was less than 21 days in apple puree and stomach content and 28 days in water while B. abortus remained viable at day 132 in milk, blood, spinach and minced meat. CONCLUSIONS: A direct PCR analysis without enrichment of bacteria saves at least 3 days. However, the limit of detection between direct PCR and plate count differs in a 10 fold range. We conclude that this lower sensitivity is acceptable in most cases especially if quick analysis are required.
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| 869. |
- Kaihola, Helena, 1969-, et al.
(författare)
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Levels of caspase-3 and histidine-rich glycoprotein in the embryo secretome as biomarkers of good-quality day-2 embryos and high-quality blastocysts
- 2019
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:12
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Tidskriftsartikel (refereegranskat)abstract
- Morphological assessment at defined developmental stages is the most important method to select viable embryos for transfer and cryopreservation. Timing of different developmental stages in embryo development has been shown to correlate with its potential to develop into a blastocyst. However, improvements in pregnancy rates by using time-lapse techniques have been difficult to validate scientifically. Therefore, there is a need for new methods, preferably non-invasive methods based on metabolomics, genomics and proteomics, to improve the evaluation of embryo quality even further. The aim of this study was to investigate if different levels of caspase-3 and histidine-rich glycoprotein (HRG), secreted by the embryo into the culture media, can be used as biomarkers of embryo quality. In this study, a total of 334 samples of culture media were collected from in vitro fertilization (IVF) treatments at three different clinics. Protein analysis of the culture media was performed using multiplex proximity extension protein analysis to detect levels of caspase-3 and HRG in the embryo secretome. Protein levels were compared in secretome samples from high- and low-quality blastocysts and embryos that became arrested during development. Correlation between protein levels and time to morula formation was also analyzed. Furthermore, protein levels in secretomes from day-2 cultured embryos were compared on the basis of whether or not pregnancy was achieved. The results showed that caspase-3 levels were lower in secretomes from high-quality vs. low-quality blastocysts and those that became arrested (p ≤ 0.05 for both). In addition, higher HRG levels correlated with a shorter time to morula formation (p ≤ 0.001). Caspase-3 levels were also lower in secretomes from day-2 cultured embryos resulting in a pregnancy vs. those that did not (p ≤ 0.05). Furthermore, it was shown that caspase-3 might be used as a marker for predicting potential success rate after transfer of day-2 cultured embryos, where a caspase-3 cutoff level of 0.02 gave a prediction probability of 68% (p = 0.038). In conclusion, in future prediction models, levels of caspase-3 and HRG might be used as potential markers of embryo quality, and secreted caspase-3 levels could to some extent predict the outcome after transfer of day-2 cultured embryos.
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| 870. |
- Kallner, Anders, et al.
(författare)
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An experimental study of methods for the analysis of variance components in the inference of laboratory information
- 2020
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : TAYLOR & FRANCIS LTD. - 0036-5513 .- 1502-7686. ; 80:1, s. 73-80
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Tidskriftsartikel (refereegranskat)abstract
- Measurement uncertainty (MU) can be estimated and calculated by different procedures, representing different aspects and intended use. It is appropriate to distinguish between uncertainty determined under repeatability and reproducibility conditions, and to distinguish causes of variation using analysis of variance components. The intra-laboratory MU is frequently determined by repeated measurements of control material(s) of one or several concentrations during a prolonged period of time. We demonstrate, based on experimental results, how such results can be used to identify the repeatability, pure reproducibility and intra-laboratory variance as the sum of the two. Native patient material was used to establish repeatability using the Dahlberg formula for random differences between measurements and an expanded Dahlberg formula if a non-random difference, e.g. bias, was expected. Repeatability and reproducibility have different clinical relevance in intensive care compared to monitoring treatment of chronic diseases, comparison with reference intervals or screening.
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