| 1. |
- Aalto, Anne, et al.
(författare)
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Brain magnetic resonance imaging does not contribute to the diagnosis of chronic neuroborreliosis
- 2007
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 48:7, s. 755-762
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Tidskriftsartikel (refereegranskat)abstract
- Background: Borrelia infections, especially chronic neuroborreliosis ( NB), may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive. Purpose: To evaluate brain magnetic resonance imaging ( MRI) in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration. Material and Methods: Sixteen well- characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1- ( with and without gadolinium), T2-, and diffusion- weighted imaging plus fluid- attenuated inversion recovery ( FLAIR) imaging were used. Results: White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls ( no significant difference). Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients ( rho=0.83, P < 0.01) and in controls ( rho=0.61, P < 0.05), but not to the duration of disease. Most lesions were detected with FLAIR, but many also with T2- weighted imaging. Conclusion: A number of MRI findings were detected in patients with chronic NB, although the findings were unspecific when compared with matched controls and did not correlate with disease duration. However, subependymal lesions may constitute a potential finding in chronic NB.
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| 2. |
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| 3. |
- Andreasen, Niels, et al.
(författare)
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Cerebrospinal fluid levels of total-tau, phospho-tau and A beta 42 predicts development of Alzheimer's disease in patients with mild cognitive impairment.
- 2003
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Ingår i: Acta neurologica Scandinavica. Supplementum. - : Hindawi Limited. - 0065-1427 .- 0001-6314. ; 179, s. 47-51
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biochemical diagnostic markers may be valuable to help in the diagnosis early in the course of Alzheimer's disease (AD), especially in the phase before clinically overt dementia, i.e. in patients with mild cognitive impairment (MCI). We studied 44 patients with MCI who, at 1-year follow-up investigation, had progressed to AD with dementia, and 32 controls. Three CSF biomarkers related to the central pathogenic processes in AD were analysed, including CSF total-tau (T-tau) (as a marker for neuronal degeneration), CSF phospho-tau (P-tau) (as a marker for hyperphosphorylation of tau and possibly for the formation of neurofibrillary tangles), and CSF A beta 42 (as a marker for A beta metabolism, and possibly for the formation of senile plaques). At baseline, 35/44 (79.5%) of the MCI patients had high CSF T-tau, 31/44 (70.4%) high CSF P-tau, while 34/44 (77.3%) had low CSF-A beta 42 levels. The positive likelihood ratio was 8.45 for CSF T-tau, 7.49 for CSF P-tau and 8.20 for CSF A beta 42. These findings suggest that these CSF-markers are abnormal before the onset of clinical dementia, and that they may help to identify MCI patients that will progress to AD. CSF diagnostic markers will be especially important when drugs with potential effects on the progression of AD (e.g. gamma-secretase inhibitors) will reach the clinical phase.
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| 4. |
- Bernardo, Ricardo, et al.
(författare)
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Combined solar and membrane drying technologies for sustainable fruit preservation in low-income countries – prototype development, modelling, and testing
- 2021
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Ingår i: Solar Energy Advances. - : Elsevier BV. - 2667-1131. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- This investigation consisted of developing and evaluating solar dryers together with semi-permeable membrane pouches for drying juicy fruits in low-income tropical countries. Two design iterations were carried out including prototype modelling and testing. The latest developed solar dryers were a passive and an active solar dryer. Modelling was initially carried out mathematically using an equation solver software followed by computational fluid dynamics. Preliminary measurements were carried out on a small-scale solar dryer. Thereafter, full-scale models were developed and tested, both in laboratory and in real conditions in Mozambique. Results from modelling were validated against measurements in laboratory in Sweden and field trials in Mozambique. Prototype building and testing in Mozambique was undertaken in collaboration with local farmers and a university. Measurement results show that the dryers help to prevent microbial growth through increased temperatures. The drying flux was increased by 50% for the passive, and by 100% for the active solar dryers compared to the ambient controls that did not use a solar dryer. The total drying time was below four days for all pouches in the dryers. The active solar dryer was shown to have the shortest drying time and the highest capacity (more pouches) but also the highest costs. Mould growth and juice fermentation were observed on control pouches drying in open air. These problems were solved with the use of solar dryer technology. However, some challenges with the membrane pouches require further development including degradation of the membrane when exposed to direct sunlight.
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| 5. |
- Blennow, Kaj, 1958, et al.
(författare)
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No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression.
- 2000
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Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 107:8-9, s. 1065-79
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Tidskriftsartikel (refereegranskat)abstract
- A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the alpha2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE epsilon4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE epsilon4 allele. No change in A2M exon 17-18 mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.
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| 6. |
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| 7. |
- Davidsson, Henrik, et al.
(författare)
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Towards a homogenous drying rate using a solar fruit dryer
- 2017
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Ingår i: ISES, International solar energy society, Solar World Congress 29 Oct – 02 Nov 2017, Abu Dhabi, UAE. - Freiburg, Germany : International Solar Energy Society. - 9783981465976
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Konferensbidrag (refereegranskat)abstract
- Solar fruit drying has the potential to reduce food insecurity in developing nations. One possible technique for drying fruit is to use solar dryers. This technique is easy to use without requiring high investments. However, the drying technique can be challenging. One problem is that the drying rate could be different depending on where in the dryer the process takes place. At the beginning of the dryer, the air is dry and warm while at the exit it has picked up moisture from the products and has cooled down. This could result in severe problems for the user. One possible solution is to have an arrangement that inverts the direction of the airflow periodically. This means that the entrance and the exit of the air are shifted. Thus, the drying rate evens out. Results from the performed simulations shows that the difference in drying rate comparing the fastest with the slowest drying rate in the dryer can be reduced from approximately 110 % to 10 % with this approach. Furthermore, this paper also describes how weather condition for a design day was established. This weather condition can be used for more accurate estimates regarding drying rates and temperatures in the solar dryer.
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| 8. |
- Davidsson, Pia, 1962, et al.
(författare)
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Clinical mass spectrometry in neuroscience. Proteomics and peptidomics.
- 2003
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Ingår i: Cellular and molecular biology (Noisy-le-Grand, France). - 0145-5680 .- 1165-158X. ; 49:5, s. 681-8
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Forskningsöversikt (refereegranskat)abstract
- In this review we discuss the merits and drawbacks with the use of proteomic and peptidomic strategies for identification of proteins and peptides in their multidimensional interactions in complex biological processes. The progress in proteomics and peptidomics during the last years offer us new challenges to study changes in the protein and peptide synthesis. These strategies also offer new tools to follow post-translational modifications and other disturbed chemical processes that may be indicative of pathophysiological alteration(s). Furthermore these techniques can contribute to improvements in the diagnosis and therapy of neurodegenerative diseases, such as Alzheimer's disease, and psychiatric diseases, as depression and post traumatic stress disorders. We also consider different practical aspects of the applications of mass spectrometry in clinical neuroscience, illustrated by example from our laboratories. The new proteomic and peptidomic strategies will further enable the progress for clinical neuroscience research.
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| 9. |
- Davidsson, Pia, 1962, et al.
(författare)
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Proteome analysis of cerebrospinal fluid proteins in Alzheimer patients.
- 2002
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Ingår i: Neuroreport. - : Ovid Technologies (Wolters Kluwer Health). - 0959-4965. ; 13:5, s. 611-5
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Tidskriftsartikel (refereegranskat)abstract
- By comparing the CSF proteome between Alzheimer disease (AD) patients and controls it may be possible to identify proteins that play a role in the disease process and thus to study the pathogenesis of AD. We used mini-gel technology in a two-dimensional electrophoresis procedure, sensitive SYPRO Ruby staining and mass spectrometry for clinical screening of disease-influenced CSF proteins in 15 AD patients and 12 controls. The levels of six proteins and their isoforms, including proapolipoprotein, apolipoprotein E, beta-2 microglobulin, retinol-binding protein, transthyretin, and ubiquitin, were significantly altered in CSF of AD patients. The most prominently altered proteins were the apolipoproteins, especially proapolipoprotein.
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| 10. |
- Davidsson, Pia, 1962, et al.
(författare)
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Proteome studies of human cerebrospinal fluid and brain tissue using a preparative two-dimensional electrophoresis approach prior to mass spectrometry.
- 2001
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Ingår i: Proteomics. - 1615-9853. ; 1:3, s. 444-52
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Tidskriftsartikel (refereegranskat)abstract
- A preparative proteomic approach, involving liquid phase isoelectric focusing (IEF) in combination with one-dimensional electrophoresis and electroelution followed by mass spectrometry and database searches, was found to be an important tool for identifying low-abundant proteins (microgram/L) in human cerebrospinal fluid (CSF) and membrane proteins in human frontal cortex. Several neuron-related proteins, such as amyloid precursor-like protein, chromogranins A and B, glial fibrillary acid protein, beta-trace, transthyretin, ubiquitin, and cystatin C, were identified in CSF. Several types of proteins were also characterized from a detergent-solubilized human frontal cortex homogenate including membrane proteins such as synaptophysin, syntaxin and Na+/K+ ATPase. One-third of the identified proteins have not previously been identified in human CSF or human frontal cortex using proteomic techniques. The absence of these proteins in two-dimensional electrophoresis maps might be due to insufficient amounts or low solubility. The advantages of using preparative liquid phase electrophoretic separations for identifying proteins from complex biological mixtures are speed of analysis, high loadability in the IEF separation, nondiscrimination of membrane proteins or low abundance proteins, yielding sufficient amounts for characterization by mass spectrometry. The use of this strategy in proteome studies of CSF/brain tissue is expected to offer new perspectives in studies of the pathology of neurodegenerative diseases, and reveal new potential markers for brain disorders.
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| 11. |
- Davidsson, Pia, 1962, et al.
(författare)
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Proteomics of Apolipoproteins and Associated Proteins From Plasma High-Density Lipoproteins.
- 2009
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Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636.
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Tidskriftsartikel (refereegranskat)abstract
- Proteomics studies have extended the list of identified apolipoproteins and associated proteins present in HDL and its subclasses. These proteins appear to cluster around specific functions related to lipid metabolism, inflammation, the immune system, hormone-binding, hemostasis, and antioxidant properties. Small studies suggest that there are substantial differences between the HDL proteome from cardiovascular disease patients and that from controls. Furthermore, dyslipidemia therapy shifts the HDL proteome from patients toward the profile observed in healthy controls. In addition, the proteome of HDL and LDL from patients with insulin resistance and peripheral atherosclerosis show significant differences with that of matched healthy controls. The proteome HDL and LDL density subclasses have apolipoproteins and associated proteins profiles that suggest subclass-specific functions. However, proteomics studies of lipoproteins are few and small and should be interpreted with caution. Nonetheless rapid technical progress in proteomic platforms suggest that soon analysis time will be reduced and precise measurement of identified proteins will be possible. This, combined with controlled purification steps of HDL and its subclasses should provide further information about proteins involved in the particles postulated spectrum of functions, including those believed to be atheroprotective.
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| 12. |
- Davidsson, Pia, et al.
(författare)
-
Vascular endothelial growth factor-D plasma levels and VEGFD genetic variants are independently associated with outcomes in patients with cardiovascular disease
- 2023
-
Ingår i: Cardiovascular Research. - : Oxford University Press. - 0008-6363 .- 1755-3245. ; 119:7, s. 1596-1605
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Tidskriftsartikel (refereegranskat)abstract
- Aims The vascular endothelial growth factor (VEGF) family is involved in pathophysiological mechanisms underlying cardiovascular (CV) diseases. The aim of this study was to investigate the associations between circulating VEGF ligands and/or soluble receptors and CV outcome in patients with acute coronary syndrome (ACS) and chronic coronary syndrome (CCS).Methods and results Levels of VEGF biomarkers, including bFGF, Flt-1, KDR (VEGFR2), PlGF, Tie-2, VEGF-A, VEGF-C, and VEGF-D, were measured in the PLATO ACS cohort (n = 2091, discovery cohort). Subsequently, VEGF-D was also measured in the STABILITY CCS cohort (n = 4015, confirmation cohort) to verify associations with CV outcomes. Associations between plasma VEGF-D and outcomes were analysed by multiple Cox regression models with hazard ratios (HR [95% CI]) comparing the upper vs. the lower quartile of VEGF-D. Genome-wide association study (GWAS) of VEGF-D in PLATO identified SNPs that were used as genetic instruments in Mendelian randomization (MR) meta-analyses vs. clinical endpoints. GWAS and MR were performed in patients with ACS from PLATO (n = 10 013) and FRISC-II (n = 2952), and with CCS from the STABILITY trial (n = 10 786). VEGF-D, KDR, Flt-1, and PlGF showed significant association with CV outcomes. VEGF-D was most strongly associated with CV death (P = 3.73e-05, HR 1.892 [1.419, 2.522]). Genome-wide significant associations with VEGF-D levels were identified at the VEGFD locus on chromosome Xp22. MR analyses of the combined top ranked SNPs (GWAS P-values; rs192812042, P = 5.82e-20; rs234500, P = 1.97e-14) demonstrated a significant effect on CV mortality [P = 0.0257, HR 1.81 (1.07, 3.04) per increase of one unit in log VEGF-D].Conclusion This is the first large-scale cohort study to demonstrate that both VEGF-D plasma levels and VEGFD genetic variants are independently associated with CV outcomes in patients with ACS and CCS. Measurements of VEGF-D levels and/or VEGFD genetic variants may provide incremental prognostic information in patients with ACS and CCS.
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| 13. |
- Gottfries, Johan, et al.
(författare)
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Proteomics for drug target discovery
- 2004
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Ingår i: Chemometrics and Intelligent Laboratory Systems. - : Elsevier B.V.. - 0169-7439. ; 73:1, s. 47-53
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Tidskriftsartikel (refereegranskat)abstract
- Proteomics, genomics and metabonomics have, during the last decade, provided researchers with huge amounts of data. The choice of transformation of such data into useful information is dependent on the study aims and objectives. In the present study, projection methods (i.e., Principal Components Analysis [PCA] and Partial List Squares-Discriminant Analysis [PLS-DA]) were used to overview results from two-dimensional (2D) protein gel separations. The aim was to unravel possibilities for target discovery options via an in-depth understanding of quantified alterations in tissue or body fluid sample protein levels related to diseases. Two examples will be included comprising (1) data measured in cerebrospinal fluid (CSF) samples from diagnosed dementia patients and healthy volunteers, and (2) data from liver samples of drug-treated animals (i.e., Rosigltazone and Wy14643). The examples reveal clear clustering, using the protein levels as input, coinciding with the clinical diagnoses in example 1 and by treatment group in example 2.
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| 14. |
- Hage, Camilla, et al.
(författare)
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Metabolomic Profile in HFpEF vs HFrEF Patients
- 2020
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Ingår i: Journal of Cardiac Failure. - : Elsevier BV. - 1071-9164 .- 1532-8414. ; 26:12, s. 1050-1059
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heart failure with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are associated with metabolic derangements, which may have different pathophysiological implications.Methods and Results: In new-onset HFpEF (EF of >= 50%, n = 46) and HFrEF (EF of <40%, n = 75) patients, 109 endogenous plasma metabolites including amino acids, phospholipids and acylcarnitines were assessed using targeted metabolomics. Differentially altered metabolites and associations with clinical characteristics were explored. Patients with HFpEF were older, more often female with hypertension, atrial fibrillation, and diabetes compared with patients with HFrEF. Patients with HFpEF displayed higher levels of hydroxyproline and symmetric dimethyl arginine, alanine, cystine, and kynurenine reflecting fibrosis, inflammation and oxidative stress. Serine, cGMP, cAMP, L-carnitine, lysophophatidylcholine (18:2), lactate, and arginine were lower compared with patients with HFrEF. In patients with HFpEF with diabetes, kynurenine was higher (P = .014) and arginine lower (P = .014) vs patients with no diabetes, but did not differ with diabetes status in HFrEF. Decreasing kynurenine was associated with higher eGFR only in HFpEF (P-interaction = .020).Conclusions: Patients with new-onset HFpEF compared with patients with new-onset HFrEF display a different metabolic profile associated with comorbidities, such as diabetes and kidney dysfunction. HFpEF is associated with indices of increased inflammation and oxidative stress, impaired lipid metabolism, increased collagen synthesis, and downregulated nitric oxide signaling. Together, these findings suggest a more predominant systemic microvascular endothelial dysfunction and inflammation linked to increased fibrosis in HFpEF compared with HFrEF.
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| 15. |
- Jaensson Gyllenbäck, Elin, et al.
(författare)
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Small intestinal CD103(+) dendritic cells display unique functional properties that are conserved between mice and humans
- 2008
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 205:9, s. 2139-2149
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Tidskriftsartikel (refereegranskat)abstract
- A functionally distinct subset of CD103(+) dendritic cells (DCs) has recently been identified in murine mesenteric lymph nodes (MLN) that induces enhanced FoxP3(+) T cell differentiation, retinoic acid receptor signaling, and gut-homing receptor (CCR9 and alpha 4 beta 7) expression in responding T cells. We show that this function is specific to small intestinal lamina propria (SI-LP) and MLN CD103(+) DCs. CD103(+) SI-LP DCs appeared to derive from circulating DC precursors that continually seed the SI- LP. BrdU pulse-chase experiments suggested that most CD103(+) DCs do not derive from a CD103(-) SI- LP DC intermediate. The majority of CD103(+) MLN DCs appear to represent a tissue- derived migratory population that plays a central role in presenting orally derived soluble antigen to CD8(+) and CD4(+) T cells. In contrast, most CD103(+) MLN DCs appear to derive from blood precursors, and these cells could proliferate within the MLN and present systemic soluble antigen. Critically, CD103(+) DCs with similar phenotype and functional properties were present in human MLN, and their selective ability to induce CCR9 was maintained by CD103(+) MLN DCs isolated from SB Crohn ' s patients. Thus, small intestinal CD103(+) DCs represent a potential novel target for regulating human intestinal infl ammatory responses.
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| 16. |
- Karlsson, Helen, 1961-
(författare)
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Lipoproteomics : A New Approach to the Identification and Characterization of Proteins in LDL and HDL
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A proteomic approach was applied to examine the protein composition of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in humans. LDL and HDL were isolated by density gradient ultracentrifugation, and proteins were separated with twodimensional gel electrophoresis (2-DE) and identified with peptide mass fingerprinting, using matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and with amino acid sequencing using electrospray ionization tandem mass spectrometry. To improve the identification of low abundant proteins in silver stained 2-DE gels, 2,5-dihydroxybenzoic acid was used instead of α-cyano-4-hydroxycinnamic acid as matrix in the peptide mass fingerprinting procedure; this was demonstrated to give more matching peptide peaks, higher sequence coverage, and higher signal to noise ratio. Altogether 18 different proteins were demonstrated in LDL and/or HDL: three of these (calgranulin A, lysozyme C and transthyretin) have not been identified in LDL before. Apo C-II, apo C-III, apo E, apo A-I, apo A-IV, apo J, apo M, serum amyloid A-IV and α1-antitrypsin were found in both LDL and HDL, while apo B-100 (clone), calgranulin A, lysozyme C and transthyretin were found only in LDL, and apo A-II, apo C-I, and serum amyloid A only in HDL. Salivary α-amylase wass identified only in HDL2, and apo L and glycosylated apo A-II only in HDL3. Many of the proteins occurred in a number of isoforms: in all, 47 different isoform identities were demonstrated. A 2-DE mobility shift assay and deglycosylation experiments were used to demonstrate, for the first time, that apo M in LDL and HDL occurs in five isoforms; three that are both N-glycosylated and sialylated, one that is N-glycosylated but not sialylated and one that is neither N-glycosylated nor sialylated. LDL from obese subjects was found to contain more apo J, apo C-II, apo M, α1-antitrypsin and serum amyloid A-IV than LDL from controls,, and also more of an acidic isoform (pI/Mr; 5.2 / 23 100) of apo A-I. In addition, the new LDLassociated protein transthyretin, was found to be significantly more abundant in LDL from obese subjects. On the other hand, the amounts of apo A-IV and the major isoform of apo A-I (pI/Mr; 5.3 / 23 100) were significantly less. Altogether, these findings (i) illustrate the power of 2-DE and mass spectrometry for detailed mapping of the proteins and their isoforms in human lipoproteins; (ii) demonstrate the presence of a number of new proteins in LDL (calgranulin A, lysozyme C and transthyretin); (iii) give precise biochemical clues to the polymorphism of apo M in LDL and HDL, and; (iv) indicate that obesity is associated with significant changes in the protein profile of LDL. It is concluded that new information on lipoproteins can easily be obtained through a proteomic approach, thus facilitating the development of a new proteomic field: lipoproteomics. Much further investigation in this field is warranted, particularly because newly discovered LDL and HDL proteins may play hitherto unknown role(s) in inflammatory reactions of the arterial wall and evolve as useful biomarkers in cardiovascular disease.
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| 17. |
- Löfgren, Lars, et al.
(författare)
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Patient-Centric Quantitative Microsampling for Accurate Determination of Urine Albumin to Creatinine Ratio (UACR) in a Clinical Setting
- 2024
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Ingår i: The Journal of Applied Laboratory Medicine. - : Oxford University Press (OUP). - 2576-9456 .- 2475-7241. ; 9:2, s. 329-341
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Tidskriftsartikel (refereegranskat)abstract
- Background: Developing and implementing new patient-centric strategies for drug trials lowers the barrier to participation for some patients by reducing the need to travel to research sites. In early chronic kidney disease (CKD) trials, albuminuria is the key measure for determining treatment effect prior to pivotal kidney outcome trials. Methods: To facilitate albuminuria sample collection outside of a clinical research site, we developed 2 quantitative microsampling methods to determine the urinary albumin to creatinine ratio (UACR). Readout was performed by LC-MS/MS. Results: For the Mitra device the within-batch precision (CV%) was 2.8% to 4.6% and the between-batch precision was 5.3% to 6.1%. Corresponding data for the Capitainer device were 4.0% to 8.6% and 6.7% to 9.0%, respectively. The storage stability at room temperature for 3 weeks was 98% to 103% for both devices. The recovery for the Mitra and Capitainer devices was 104% (SD 7.0%) and 95 (SD 7.4%), respectively. The inter-assay comparison of UACR assessment generated results that were indistinguishable regardless of microsampling technique. The accuracy based on LC-MS/MS vs analysis of neat urine using a clinical chemistry analyzer was assessed in a clinical setting, resulting in 102 ± 8.0% for the Mitra device and 95 ± 10.0% for the Capitainer device. Conclusions: Both UACR microsampling measurements exhibit excellent accuracy and precision compared to a clinical chemistry analyzer using neat urine. We applied our patient-centric sampling strategy to subjects with heart failure in a clinical setting. Precise UACR measurements using quantitative microsampling at home would be beneficial in clinical drug development for kidney therapies.
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| 18. |
- Nguyen, Duong T., et al.
(författare)
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Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Despite improvements in pre-clinical drug testing models, predictability of clinical outcomes continues to be inadequate and costly due to poor evidence of drug metabolism. Humanized miniature organs integrating decellularized rodent organs with tissue specific cells are translational models that can provide further physiological understanding and evidence. Here, we evaluated 4-Flow cannulated rat hearts as the fundamental humanized organ model for cardiovascular drug validation. Results show clearance of cellular components in all chambers in 4-Flow hearts with efficient perfusion into both coronary arteries and cardiac veins. Furthermore, material characterization depicts preserved organization and content of important matrix proteins such as collagens, laminin, and elastin. With access to the complete vascular network, different human cell types were delivered to show spatial distribution and integration into the matrix under perfusion for up to three weeks. The feature of 4-Flow cannulation is the preservation of whole heart conformity enabling ventricular pacing via the pulmonary vein as demonstrated by noninvasive monitoring with fluid pressure and ultrasound imaging. Consequently, 4-Flow hearts surmounting organ mimicry challenges with intact complexity in vasculature and mechanical compliance of the whole organ providing an ideal platform for improving pre-clinical drug validation in addition to understanding cardiovascular diseases.
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| 19. |
- Nilselid, A.-M., et al.
(författare)
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Clusterin in cerebrospinal fluid : Analysis of carbohydrates and quantification of native and glycosylated forms
- 2006
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Ingår i: Neurochemistry International. - : Elsevier BV. - 0197-0186 .- 1872-9754. ; 48:8, s. 718-28
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Tidskriftsartikel (refereegranskat)abstract
- Clusterin is suggested to be involved in the pathogenesis of Alzheimer's disease. Clusterin expression is increased in brain tissue in affected regions of Alzheimer patients, and intense clusterin staining is found in both senile plaques and in neuronal and glia cells. In contrast, the cerebrospinal fluid level of clusterin in Alzheimer patients has, thus far, been found unchanged. Clusterin is a glycosylated protein, and an alteration of its glycosylation in Alzheimer's disease might influence accurate quantification in cerebrospinal fluid through interference of antibody binding to the protein. Using enzymatic deglycosylation of clusterin isolated from cerebrospinal fluid, we found that the carbohydrates attached to clusterin were of the N-linked type and sialic acids. Based on this finding, cerebrospinal fluid samples from Alzheimer patients (n = 99) and controls (n = 39) were analysed. The samples were treated with peptide: N-glycanase F, cleaving off N-linked carbohydrates, and clusterin was quantified before and after deglycosylation using a new sandwich enzyme-linked immunosorbent assay. Clusterin was significantly increased in Alzheimer patients, in both native (7.17 ± 2.43 AU versus 5.73 ± 2.09 AU, p = 0.002), and deglycosylated samples (12.19 ± 5.00 AU versus 9.68 ± 4.38 AU, p = 0.004). Deglycosylation led to increased measured levels of clusterin by 70% (p < 0.001) in Alzheimer patients and 67% (p < 0.001) in controls. These findings indicate that glycosylation of proteins may interfere with their quantification. The results show that clusterin is significantly increased in cerebrospinal fluid from Alzheimer patients as a group, supporting that clusterin might be involved in the pathogenesis of Alzheimer's disease. However, the individual clusterin levels overlap between the two groups, and thus cerebrospinal fluid clusterin measurement is not suitable as a biochemical marker in the diagnosis of Alzheimer's disease. © 2006 Elsevier Ltd. All rights reserved.
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| 20. |
- Olson, Fredrik J., 1975, et al.
(författare)
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Consistent differences in protein distribution along the longitudinal axis in symptomatic carotid atherosclerotic plaques.
- 2010
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 401:4, s. 574-80
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Tidskriftsartikel (refereegranskat)abstract
- Identifying proteins associated with a complicated atherosclerotic plaque phenotype would provide potential biomarkers for detection of patients at elevated risk for clinically overt disease. We hypothesized that the protein content of carotid atherosclerotic tissue differs between complicated segments located in the internal carotid artery (ICA) and more stable segments in the common carotid artery (CCA). Using differential proteomics, we aimed to identify proteins differentially expressed between these segments of symptomatic carotid plaques. Ten snap-frozen human endarterectomies were divided into ICA and CCA segments and compared using two-dimensional differential gel electrophoresis and liquid chromatography-mass spectrometry. This study setup allowed pair-wise comparison of complicated and more stable atherosclerotic tissue from the same individual. We identified 19 proteins with differential distribution between ICA and CCA segments. Among the proteins more abundant in ICA were S100A10, ferritin light chain and fibrinogen. Among the proteins more abundant in CCA were ApoE, actin and l-lactate dehydrogenase B. Immunohistochemical staining revealed that S100A10 was expressed in endothelial cells, in clusters of macrophages and foam cells, and co-localized with the urokinase-type plasminogen activator receptor, uPAR. In conclusion, the results support the concept of comparing segments within plaques. The identified proteins constitute potential markers of complicated atherosclerotic lesions. The previously reported function of S100A10 to regulate plasmin activity affecting both angiogenesis and macrophage invasion, together with our observation of its accumulation in complicated plaque segments, warrants further studies of its potential role as a drug target for treatment of advanced atherosclerosis.
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| 21. |
- Otte, Pia Piroschka, et al.
(författare)
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Facilitating integrated agricultural technology development through participatory research
- 2018
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Ingår i: Journal of Agricultural Education and Extension. - 1389-224X. ; 24:3, s. 285-299
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In this paper, we discuss the role of participatory research in integrated agricultural technology development using the example of a solar fruit drying project in Mozambique. Design/methodology/approach: We engage in seven participatory exercises with groups of farmers from two farmers’ associations in Inharrime district in Mozambique to identify their needs for solar fruit drying that are crucial for solar dryer technology design. We focus in the analysis on three of these exercises including a daily schedule exercise, SWOT (Strengths Weaknesses Opportunities and Threats) analysis and technology requirement exercise. Findings: Participatory research takes a dual function for integrated agricultural technology development. First, it can help to identify the technology needs of farmers and second it can enable the exchange and creation of different sets of knowledge for agricultural technology development between multiple stakeholders. Practical implications: Participatory research provides a tool for joint knowledge exchange and creation, which allows the identified technology requirements to be translated into practical technology design. Theoretical implications: This paper extends the concept of integrated research to integrated agricultural technology development and shows how participatory research is a tool that enables transdisciplinarity, which presents the most desired form of integrated research. Originality: This research is highly relevant for researchers working in an interdisciplinary environment with agricultural technology development in cross-cultural contexts. From a meta-level perspective, it provides insights for joint and integrated technology development.
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| 22. |
- Otte, Pia Piroschka, et al.
(författare)
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The importance of gender roles and relations in rural agricultural technology development : a case study on solar fruit drying in Mozambique
- 2018
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Ingår i: Gender, Technology and Development. - : Informa UK Limited. - 0971-8524 .- 0973-0656. ; 22:1, s. 40-58
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Tidskriftsartikel (refereegranskat)abstract
- Many agricultural technology interventions that aim to improve farmers’ livelihoods focus on households as the unit of analysis and ignore gender roles that entail different benefits and costs for different household members. Agricultural projects have shown limited success where gender roles and relations were ignored and thus more gender sensitive research is needed in agricultural technology development to ensure social acceptance. In this study, we address this need by investigating the importance of gender roles and relations in the case of solar fruit drying in Mozambique. We apply a variety of gender sensitive participatory methods that enable farmers to actively take part in the technology development process. First results indicate that the costs and benefits of solar fruit drying are not shared equally between genders. Women have much less time available for using the solar fruit dryer. The data also indicate that certain steps in the solar fruit drying process are clearly gender divided. We finally discuss potential mechanisms that can be applied in agricultural technology projects that can create awareness of the risk to reproduce traditional gender roles and unequal relations in the development process of new agricultural technologies.
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| 23. |
- Paulson, Linda, 1971, et al.
(författare)
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Comparative genome- and proteome analysis of cerebral cortex from MK-801-treated rats.
- 2003
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Ingår i: Journal of neuroscience research. - : Wiley. - 0360-4012 .- 1097-4547. ; 71:4, s. 526-33
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Tidskriftsartikel (refereegranskat)abstract
- cDNA microarrays and two-dimensional gel-electrophoresis in combination with mass spectrometry, were used to screen alterations in mRNA and protein levels, respectively, in cerebral cortex of MK-801-treated rats. The rats were divided in two groups; group 1 (short-term treated) and group 2 (long-term treated). In group 1, four genes were up-regulated and five down-regulated. In group 2, seven genes were up-regulated and six down-regulated. In group 1, the levels of one protein was increased and eight proteins reduced. In group 2, the levels of two proteins were increased and four proteins reduced. Several of the altered genes (casein kinase 2, glutamic acid decarboxylase, synaptotagmin, gamma aminobutyric acid [GABA] transporter, creatine kinase, and cytochrome c oxidase) and proteins (superoxide dismutase, hsp 60, hsp 72 and gamma-enolase) have previously been connected to schizophrenia. Alterations of the genes (microglobulin, c-jun proto-oncogene, 40S ribosomal protein S19, adenosine diphosphate (ADP)-ribosylation factors, platelet-derived growth factor, fructose-bisphophate aldolase A, and myelin proteolipid) and the proteins (stathmin, H+-transp. Adenosine triphosphate (ATP) synthase, pyruvate dehydrogenase, beta-actin and alpha-enolase), have not, to our knowledge, earlier been implicated in schizophrenia pathology. Overall, these results with a combined approach of genomics and proteomics add to the validity of subchronic N-methyl-D-aspartate (NMDA)-receptor antagonist treatment as an animal model of schizophrenia.
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| 24. |
- Paulson, Linda, 1971, et al.
(författare)
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Comparative proteome analysis of thalamus in MK-801-treated rats.
- 2004
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Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 4:3, s. 819-25
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Tidskriftsartikel (refereegranskat)abstract
- Two-dimensional gel-electrophoresis in combination with mass spectrometry is a powerful approach to compare protein expression in brain tissues. Using this proteomic approach, and based on the hypothesis that schizophrenia involves hypoglutamergic brain function, alterations in protein levels in the thalamus of rats treated with the N-methyl-D-aspartate (NMDA) receptor antagonist [+]-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]-cycloheptene-5,10-iminehydrogenmaleate (MK-801), as compared to saline-treated animals, were assessed in an unbiased fashion. The rats were divided into two groups; group 1 (short-term treated) and group 2 (long-term treated). In group 1, the levels of seven proteins were increased and four proteins reduced. In group 2, the levels of six proteins were reduced. Several of the altered proteins (heat shock proteins 60 and 72, albumin, dihydropyrimidinase related protein-2, aldolase c, and malate dehydrogenase) have previously been connected to schizophrenia. Alterations of other proteins (dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex E2, guanine deaminase, alpha-enolase, aconitase, ATP-synthase and alpha-internexin), have not, to the best of our knowledge, earlier been implicated in schizophrenia pathology. Our results show the high potential of using proteomic methods for the validation of animal models of schizophrenia and to identify new proteins involved in the pathophysiological mechanisms of schizophrenia.
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| 25. |
- Paulson, Linda, 1971, et al.
(författare)
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Effects on rat thalamic proteome by acute and subchronic MK-801-treatment.
- 2004
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Ingår i: European journal of pharmacology. - : Elsevier BV. - 0014-2999. ; 505:1-3, s. 103-9
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Tidskriftsartikel (refereegranskat)abstract
- Since the symptoms of intoxication with non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists closely mimic symptoms in patients with schizophrenia, [+]-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]-cycloheptene-5,10-iminehydrogenmaleate (MK-801)-treated rodents are often used as a model for schizophrenia. In most studies, acute injections of MK-801 to rats have been used, but in some studies, longer periods of treatment have been performed. In our previous work, alterations in mRNA/protein expression were screened in the cerebral cortex of MK-801 treated rats. Different proteins were altered in different treatment courses of MK-801. The main objective of the present study was to evaluate different treatment periods of treatment with MK-801 in rats as a model for schizophrenia. Thalamus proteins from treated (acute, six and 12 days) and control rats were analyzed with two-dimensional gel electrophoresis and mass spectrometry. Our results show that different treatment times of MK-801 to rats give different biochemical results. Therefore, it is important to use the same treatment time in studies that will be compared.
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