| 1. |
- Abusibaa, W. A., et al.
(författare)
-
Expression of the GBGT1 Gene and the Forssman Antigen in Red Blood Cells in a Palestinian Population
- 2019
-
Ingår i: Transfusion Medicine and Hemotherapy. - : S. Karger AG. - 1660-3796 .- 1660-3818. ; 46:6, s. 450-454
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The Forssman antigen (FORS1 Ag) is expressed on human red blood cells (RBCs). We investigated its presence on RBCs from Palestinian subjects and Swedish subjects by serological testing and by sequencing part of exon 7 of the GBGT1 gene, which encodes Forssman synthase. -Materials and Methods: Blood samples from Palestinian subjects (n = 211 adults and n = 73 newborns) and from Swedish subjects (n = 47 adults) were analyzed in the study. RBCs from the Palestinian samples were typed for the FORS1 Ag using a monoclonal anti-Forssman antibody. The GBGT1 gene was genotyped by DNA sequencing (all adult samples) or by using amplification refractory mutation system PCR (newborn samples). Results: All of the studied samples were negative for the FORS1 Ag by serologic typing. DNA sequencing of the 3′ end of exon 7 of the GBGT1 gene, which includes Arg296, showed that all samples had the wild-type Arg296 sequence, which is associated with an inactive form of Forssman synthase. We detected four single nucleotide polymorphisms in the adult samples; two were silent (p.Tyr232=, p.Gly290=), and two were missense (p.Arg243Cys, p.Arg243His). The allele frequencies ranged from 0.2 to 3.6%. The p.Arg243Cys SNP was a novel SNP that was detected in one Palestinian sample. Conclusion: Our results confirmed the allelic diversity of GBGT1 and identified a novel nucleotide polymorphism in this gene, p.Arg243Cys. Our results also confirmed that the FORS blood group system is a low-frequency system. © 2019 S. Karger AG, Basel. Copyright: All rights reserved.
|
|
| 2. |
- Andersson Shams Hakimi, Caroline, et al.
(författare)
-
Effects of fibrinogen and platelet supplementation on clot formation and platelet aggregation in blood samples from cardiac surgery patients.
- 2014
-
Ingår i: Thrombosis research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 134:4, s. 895-900
-
Tidskriftsartikel (refereegranskat)abstract
- Bleeding after cardiac surgery may be caused by surgical factors, impaired haemostasis, or a combination of both. Transfusion of blood products is used to improve haemostasis, but little is known about what combination is optimal. We hypothesized that addition of both fibrinogen and platelets to blood samples from cardiac surgery patients would improve clot formation and platelet aggregation to a greater extent than if the components were added separately.
|
|
| 3. |
- Andersson Shams Hakimi, Caroline, et al.
(författare)
-
Effects of fibrinogen and platelet transfusion on coagulation and platelet function in bleeding cardiac surgery patients.
- 2019
-
Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 63:4, s. 475-482
-
Tidskriftsartikel (refereegranskat)abstract
- Excessive bleeding is a significant problem in cardiac surgery. Fibrinogen and platelet concentrate transfusion are used clinically to improve haemostasis and reduce bleeding but little is known about their functional effects on coagulation and platelet function in patients with ongoing bleeding.Forty-two patients with ongoing bleeding after cardiac surgery were included in an observational study. Patients received either fibrinogen concentrate (n=16), platelet concentrate (n=12), or both fibrinogen and platelets (n=14), median doses 2g fibrinogen and 2 units platelets given at one occasion. Blood samples were collected before and after transfusion. Coagulation (clotting time and clot stability) was analysed with rotational thromboelastometry, and platelet function with impedance aggregometry. In addition, platelet count and fibrinogen concentration was measured. Chest drain output was measured before and after the transfusion.Fibrinogen infusion resulted in an increase in fibrinogen concentration and clot stability (P=0.001), but had no effect on platelet aggregation. Platelet transfusion did not significantly affect coagulation, but improved arachidonic acid- and TRAP-induced platelet aggregation (P=0.017 and 0.034 respectively) and increased platelet count. Combined fibrinogen and platelet transfusion shortened clotting time (P=0.005) and increased clot stability (P=0.001), and improved arachidonic acid- and TRAP-induced platelet aggregation (P=0.004 and 0.016 respectively), and increased fibrinogen concentration and platelet count. The median bleeding volume was 150 (25th-75th percentile 70-240)mL/h before, and 60 (40-110)mL/h after transfusion of fibrinogen and/or platelet concentrate (P<0.001).The results demonstrate improved coagulation and platelet function following fibrinogen and platelet transfusion in patients bleeding after cardiac surgery.
|
|
| 4. |
- Andersson Shams Hakimi, Caroline, et al.
(författare)
-
In vitro assessment of platelet concentrates with multiple electrode aggregometry.
- 2015
-
Ingår i: Platelets. - : Informa UK Limited. - 0953-7104 .- 1369-1635. ; 26:2, s. 132-137
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT Storage impairs platelet function. It was hypothesized that multiple electrode aggregometry in vitro could be used to follow aggregability in platelet concentrates over time and that the results predict the efficacy of platelet transfusion in an ex vivo transfusion model. In vitro platelet aggregability was assessed in apheresis and pooled buffy coat platelet concentrates (BCs) (n = 13 each) using multiple electrode aggregometry with different agonists 1, 3, 5 and 7 days after preparation. In the ex vivo transfusion model, whole blood samples from nine healthy volunteers were collected every second day. The samples were supplemented with stored platelets (+146 × 10(9) × l(-1)) from the same unit 1, 3, 5 and 7 days after preparation. Platelet aggregability was assessed in the concentrate and in the whole blood samples before and after platelet supplementation. There was a continuous reduction in in vitro platelet aggregability over time in both apheresis and pooled BCs. The same pattern was observed after ex vivo addition of apheresis and pooled BCs to whole blood samples. The best correlation between in vitro aggregability and changes in aggregation after addition was achieved with collagen as agonist (r = 0.67, p
|
|
| 5. |
- Andersson Shams Hakimi, Caroline, et al.
(författare)
-
The Effect of Ex Vivo Factor XIII Supplementation on Clot Formation in Blood Samples From Cardiac and Scoliosis Surgery Patients.
- 2018
-
Ingår i: Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. - : SAGE Publications. - 1938-2723. ; 24:4, s. 677-683
-
Tidskriftsartikel (refereegranskat)abstract
- Excessive perioperative bleeding remains a substantial problem. Factor XIII (FXIII) contributes to clot stability, and it has therefore been suggested that supplementation with FXIII concentrate may improve perioperative hemostasis. We evaluated the effects of increasing doses of FXIII, alone or in combination with fibrinogen or platelet concentrate, in blood samples from 2 considerably different groups of surgical patients: cardiac and scoliosis surgery patients. Whole-blood samples were collected immediately after operation from cardiac and scoliosis surgery patients. The samples were supplemented with 3 clinically relevant doses of FXIII concentrate (+20%, +40%, and +60%), alone or in combination with a fixed dose of fibrinogen concentrate (+1.0 g/L) or fresh apheresis platelets (+92 × 10(9)/L). Clot formation was assessed with rotational thromboelastometry (ROTEM). When the highest dose of FXIII concentrate was added, EXTEM clotting time was shortened by 10% in both cardiac and scoliosis surgery patients (95% confidence intervals: 2.4%-17% and 3.3%-17%, respectively), and FIBTEM maximum clot firmness was increased by 25% (9.3%-41%) in cardiac patients, relative to baseline. When fibrinogen was added, the dose-dependent effect of FXIII on clot stability was maintained, but the total effect was markedly greater than with FXIII alone, +150% (100%-200%) and +160% (130%-200%) for the highest FXIII dose in cardiac and scoliosis patients, respectively. Ex vivo supplementation with clinically relevant doses of FXIII improved clot formation moderately in blood samples from cardiac and scoliosis surgery patients, both alone and when given in combination with fibrinogen or platelet concentrate.
|
|
| 6. |
|
|
| 7. |
- Blennow, Kaj, 1958, et al.
(författare)
-
No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression.
- 2000
-
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
-
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.
|
|
| 8. |
- Carlberg, Niclas, et al.
(författare)
-
Circulating concentrations of glycocalyx degradation products in preeclampsia
- 2022
-
Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Preeclampsia is a multisystem disorder that affects maternal endothelium. The glycocalyx lines and protects the endothelial surface. In severe systemic diseases, like sepsis, it is shed and glycocalyx degradation products can be detected in increased concentrations in plasma. The aim of this study was to compare circulating concentrations of glycocalyx degradation products in degrees of preeclampsia severity. Study design: In this observational study, we included women from the South African PROVE biobank. Women were divided into normotensive controls, women with preeclampsia without end-organ complications, women with a single end-organ complication and women with multiple end-organ complications. Plasma samples taken at inclusion after diagnosis (preeclampsia cases) or at admission for delivery (normotensive controls) were analyzed with ELISA for syndecan-1, hyaluronic acid and thrombomodulin and compared between groups. Results: Women with preeclampsia (n = 47) had increased plasma concentrations of hyaluronic acid (100.3ng/ml IQR 54.2–204 vs. 27.0ng/ml IQR (13.5–66.6), p < 0,001) and thrombomodulin (4.22ng/ml IQR 3.55–5.17 vs. 3.49ng/ml IQR 3.01–3.68, p = 0.007) but not syndecan-1 compared with normotensive women (n = 10). There were no differences in plasma concentration in any of these biomarkers in women with preeclampsia with no end-organ complications (n = 10) compared with women with preeclampsia and one end-organ complication (n = 24). Women with preeclampsia with two or more end-organ complications (n = 13) had increased plasma concentrations of thrombomodulin (5.46ng/ml, IQR 4.85–7.83 vs. 4.66ng/ml, IQR 3.45–4.88, p = 0.042) compared with women with preeclampsia and no end-organ complications. Conclusion: Thrombomodulin was associated with disease severity and may be valuable for risk-stratifying women with preeclampsia.
|
|
| 9. |
- Damén, Tor, et al.
(författare)
-
Atrial natriuretic peptide does not degrade the endothelial glycocalyx: A secondary analysis of a randomized porcine model
- 2021
-
Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 65:9, s. 1305-1312
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The atrial natriuretic peptide (ANP) released from the heart regulates intravascular volume and is suspected to increase capillary permeability. Contradictory results regarding ANP and glycocalyx degradation have been reported. The aim of this study was to investigate if an infusion of ANP causes degradation of the endothelial glycocalyx. Methods: Twenty pigs, pretreated with 250mg methylprednisolone, were randomized to receive an infusion of either ANP (50ng/kg/min) (n=10) or 0.9% NaCl (n=10) during 60min. Endothelial glycocalyx components (heparan sulphate proteoglycan and hyaluronic acid), Hct, calculated plasma volume and colloid osmotic pressure were measured from baseline to 60min. Results: There was no difference between the control and intervention groups for heparan sulphate proteoglycan and hyaluronic acid corrected for the change in plasma volume (P=.333 and 0.197). Hct increased with 1.8±2.2% in the intervention group (P=.029) with no change −0.5±2.3% in the control group (P=.504). The plasma volume decreased in the intervention group with −8.4±10% (P=.034) with no change in the control group 3.1±12% (P=.427). Median changes in colloid osmotic pressures in the control and intervention group were −0.39 [95% CI, −1.88-0.13] and 0.9 [95% CI, 0.00-1.58], respectively (P=.012). Conclusions: In this randomized porcine study, an ANP infusion did not cause endothelial glycocalyx degradation but decreased the plasma volume most probably due to precapillary vasodilation and increased filtration. © 2021 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
|
|
| 10. |
- Damén, Tor, et al.
(författare)
-
Effects of different mean arterial pressure targets on plasma volume, ANP and glycocalyx-A randomized trial.
- 2021
-
Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 65:2, s. 220-227
-
Tidskriftsartikel (refereegranskat)abstract
- Arterial haematocrit (Hct) has been shown to decrease after anaesthesia induction, most probably because of an increased plasma volume (PV). The primary objective was to quantify change in PV if mean arterial pressure (MAP) was kept at baseline level or allowed to decrease to 60mm Hg. Our secondary objective was to evaluate underlying mechanisms of this response.Twenty-four coronary artery bypass patients were randomized to a higher (90mm Hg, intervention group) or lower (60mm Hg, control group) MAP by titration of norepinephrine. During the experimental procedure, no fluids were administered. Baseline PV was measured by 125 I-albumin and the change in PV was calculated from the change in Hct. Changes in MAP, plasma 125 I-albumin, colloid osmotic pressure, albumin, Mid Regional-pro Atrial Natriuretic Peptide (MR-proANP) and endothelial glycocalyx components were measured from baseline to 50minutes after anaesthesia induction.The MAP during the trial was 93±9mm Hg in the intervention group and 62±5mm Hg in the control group. PV increased with up to 420±180mL in the control group and 45±130mL in the intervention group (P<.001). Albumin and colloid osmotic pressure decreased significantly more in the control group. MR-proANP increased in the control group but no shedding of the glycocalyx layer was detected in either of the groups.Allowing mean arterial pressure to fall to 60mm Hg during anaesthesia induction, increases the plasma volume due to reabsorption of interstitial water, with no ANP-induced degradation of the endothelial glycocalyx.
|
|
| 11. |
- Davidsson, Pia, 1962, et al.
(författare)
-
Proteome studies of human cerebrospinal fluid and brain tissue using a preparative two-dimensional electrophoresis approach prior to mass spectrometry.
- 2001
-
Ingår i: Proteomics. - 1615-9853. ; 1:3, s. 444-52
-
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.
|
|
| 12. |
- Ferreira, S., et al.
(författare)
-
FORSCells: 40-days fixed prepared reagent for detection of anti-Forssman in humans
- 2020
-
Ingår i: Journal of Immunological Methods. - : Elsevier BV. - 0022-1759. ; 478
-
Tidskriftsartikel (refereegranskat)abstract
- In 2012, the FORS system was accepted by the International Society of Blood Transfusion as the 31st blood group system. Forssman (Fs) antigen (Ag) expression is most commonly found on sheep red blood cells (RBC) but rare in human RBC. Anti-Fs antibodies (Ab) are naturally occurring in human sera and are predominantly IgM but they can also be IgG. To this day, the global prevalence of the FORS system is unknown. Currently, there is a lack of natural FORS1-positive RBC available to use for anti-Fs screening in large populations. This study was designed to produce FORS1-positive cells viable for 40 days use in the anti-Fs screening. Three to 5% FORS1-positive cells were produced using sheep's blood and CellStab stabilizer solution. The quality of the FORS1-positive cells was investigated in more than three independent experiments of ABO titration, osmotic fragility test and supernatant haemolysis. For each batch of FORS1-positive cells produced, an extended antibody panel was performed. To demonstrate that the FORS1-positive cells can be used for up to 40 days, anti-Fs screening and classification were carried out in a patient and donor population. Antigenic expression and membrane integrity of FORS1-positive cells remained stable for 40 days. Good FORS1 Ag preservation was established, and minimal haemolysis was observed. In conclusion, a novel and easy-to-produce reagent has been developed and submitted to a patent with stable FORS1 Ag expression. With this FORS1-positive cell suspension, it is now possible to screen and classify anti-Fs Ab in large populations.
|
|
| 13. |
- Halim, Adnan, et al.
(författare)
-
Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD.
- 2012
-
Ingår i: Molecular & cellular proteomics : MCP. - 1535-9484. ; 11:4
-
Tidskriftsartikel (refereegranskat)abstract
- Urine is a complex mixture of proteins and waste products and a challenging biological fluid for biomarker discovery. Previous proteomic studies have identified more than 2800 urinary proteins but analyses aimed at unraveling glycan structures and glycosylation sites of urinary glycoproteins are lacking. Glycoproteomic characterization remains difficult because of the complexity of glycan structures found mainly on asparagine (N-linked) or serine/threonine (O-linked) residues. We have developed a glycoproteomic approach that combines efficient purification of urinary glycoproteins/glycopeptides with complementary MS-fragmentation techniques for glycopeptide analysis. Starting from clinical sample size, we eliminated interfering urinary compounds by dialysis and concentrated the purified urinary proteins by lyophilization. Sialylated urinary glycoproteins were conjugated to a solid support by hydrazide chemistry and trypsin digested. Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. In CID-MS(2), Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr were typically observed, in agreement with known N-linked biantennary complex-type and O-linked core 1-like structures, respectively. Additional glycoforms for specific N- and O-linked glycopeptides were also identified, e.g. tetra-antennary N-glycans and fucosylated core 2-like O-glycans. Subsequent CID-MS(3), of selected fragment-ions from the CID-MS(2) analysis, generated peptide specific b- and y-ions that were used for peptide identification. In total, 58 N- and 63 O-linked glycopeptides from 53 glycoproteins were characterized with respect to glycan- and peptide sequences. The combination of CID and electron capture dissociation techniques allowed for the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites. We defined 29 O-glycosylation sites which have, to our knowledge, not been previously reported. This is the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt.
|
|
| 14. |
|
|
| 15. |
- Hansson, Emma C., 1985, et al.
(författare)
-
Platelet function recovery after ticagrelor withdrawal in patients awaiting urgent coronary surgery
- 2017
-
Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 51:4, s. 633-637
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Dual antiplatelet therapy with ticagrelor and aspirin is associated with an increased risk of perioperative bleeding complications. Current guidelines recommend therefore discontinuation of ticagrelor 5 days before surgery to allow sufficient recovery of platelet function. It is not known how the time to recovery varies between individual patients after discontinuation of ticagrelor. METHODS: Twenty-five patients accepted for urgent coronary artery bypass surgery and treated with ticagrelor and aspirin were included in a prospective observational study. Platelet aggregation was evaluated with impedance aggregometry at five timepoints 12-96 h after discontinuation of ticagrelor. In a subset of patients (n = 15), we also tested the ex vivo efficacy of platelet concentrate supplementation on platelet aggregation. RESULTS: There was a gradual increase in mean adenosine diphosphate-induced platelet aggregation after discontinuation of ticagrelor. After 72 h, mean aggregation was 38 +/-23 aggregation units (U), which is above a previously suggested cut-off of 22 U, when patients can be operated without increased bleeding risk. However, there was a large interindividual variability (range 488 U at 72 h) and 6/24 patients (25%) had <22 U after 72 h. Ex vivo administration of platelet concentrate did not improve adenosine diphosphate-induced aggregation at any timepoint after ticagrelor discontinuation. CONCLUSIONS: Adenosine diphosphate-induced aggregation was acceptable after 72 h in the majority of patients but with a large interindividual variability. Due to the large variability, platelet function testing may prove to be a valuable tool in timing of surgery in patients with ongoing or recently stopped ticagrelor treatment. Adenosine diphosphate-induced aggregation was not improved by addition of platelet concentrate.
|
|
| 16. |
- Hesse, Camilla, et al.
(författare)
-
The N-terminal domain of α-dystroglycan is released as a 38kDa protein and is increased in cerebrospinal fluid in patients with Lyme neuroborreliosis.
- 2011
-
Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 412:3, s. 494-499
-
Tidskriftsartikel (refereegranskat)abstract
- α-Dystroglycan is an extracellular adhesion protein that is known to interact with different ligands. The interaction is thought to stabilize the integrity of the plasma membrane. The N-terminal part of α-dystroglycan may be proteolytically processed to generate a small 38kDa protein (α-DG-N). The physiological significance of α-DG-N is unclear but has been suggested to be involved in nerve regeneration and myelination and to function as a potential biomarker for neurodegenerative and neuromuscular diseases. In this report we show that α-DG-N is released into different body fluids, such as lachrimal fluid, cerebrospinal fluid (CSF), urine and plasma. To investigate the significance of α-DG-N in CSF we examined the levels of α-DG-N and known neurodegenerative markers in CSF from patients diagnosed with Lyme neuroborreliosis (LNB) and healthy controls. In untreated acute phase LNB patients, 67% showed a significant increase of CSF α-DG-N compared to healthy controls. After treatment with antibiotics the CSF α-DG-N levels were normalized in the LNB patients.
|
|
| 17. |
- Holdfeldt, André, et al.
(författare)
-
The PAR4-derived pepducin P4Pal10 lacks effect on neutrophil GPCRs that couple to Gαq for signaling but distinctly modulates function of the Gαi-coupled FPR2 and FFAR2
- 2020
-
Ingår i: Biochemical Pharmacology. - : Elsevier BV. - 0006-2952. ; 180
-
Tidskriftsartikel (refereegranskat)abstract
- A novel mechanism of action was described for the protease-activated receptor 4 (PAR4)-derived pepducin (P4Pal10), when it was shown to exhibit inhibitory efficacy towards G protein coupling to multiple Gαq-coupled receptors (Carr, R., 3rd et al., Mol. Pharmacol. 2016(89) 94). We could confirm that P4Pal10, similar to an earlier-characterized Gαq inhibitor (YM-254890), inhibited platelet aggregation induced by agonists for the Gαq-coupled receptors PAR1 and PAR4. Next, we applied P4Pal10 as a tool compound and investigated its modulatory effect on several Gαq- and Gαi-coupled GPCRs expressed by human neutrophils. P4Pal10 had, however, no inhibitory effects on signaling downstream of the Gαq-coupled receptors for ATP (P2Y2R) and PAF (PAFR). Instead, P4Pal10 inhibited signaling downstream the Gαi-coupled FPR2. The inhibition was not due to a direct effect on Gαi as the closely related FPR1 was unaffected. In addition, we found that the pepducin activated allosterically modulated short chain fatty acid receptor (FFAR2), a Gαi/Gαq coupled GPCR that is functionally expressed in neutrophils. Taken together, we show that pepducins are unique tool-compounds for mechanistic studies of GPCR signaling and modulation in neutrophils. The data presented add also lipopeptides into the known ligand recognition lists for the two pattern recognition receptors FPR2 and FFAR2, receptors that primarily sense formylated peptides and short free fatty acids, respectively, inflammatory mediators of microbial origin. © 2020 The Authors
|
|
| 18. |
- Jesus, C., et al.
(författare)
-
Prevalence of antibodies to a new histo-blood system: the FORS system
- 2018
-
Ingår i: Blood Transfusion. - 1723-2007. ; 16:2, s. 178-183
-
Tidskriftsartikel (refereegranskat)abstract
- Background. In 1987, three unrelated English families were reported with a putative blood subgroup called A pae. Swedish researchers later found evidence leading to abolishment of the A pae subgroup and establishment instead of the FORS blood group system (System 31 -ISBT, 2012). It is important to know the prevalence of antibodies in order to make the best decisions in transfusion medicine. Cells expressing the Forssman saccharide, such as sheep erythrocytes, are needed to detect the anti-Forssman antibody. The aim of this study was to define the prevalence of human anti-Forssman antibody. Materials and methods. Plasma samples from 800 individuals were studied. Sheep erythrocytes or Forssman "kodecytes" were mixed with the plasma samples using the tube technique. Plasma from an A pae individual was used as a negative control and monoclonal anti-Forssman antibody (M1/22.25.8HL cell line supernatant) was used as the positive control. Results. Of the 800 individuals tested, one was negative for the presence of anti-Forssman antibody. We compared the anti-Forssman antibody reaction pattern between genders and found that males have weaker reactions than females, both at room temperature (p= 0.026) and at 37 degrees C (p= 0.043). We also investigated the reaction pattern of anti-Forssman antibody in relation to ABO and Rh blood group types without finding any significant differences. Discussion. Sheep erythrocytes are suitable for searching for human anti-Forssman antibody. The quantity of anti-Forssman antibodies in plasma is higher in females than in males. In the population (n= 800) studied here, we found one individual lacking the anti-Forssman antibody. These results contribute to the data already published, confirming that FORS is a rare blood group.
|
|
| 19. |
- Kunze, Angelika, 1978, et al.
(författare)
-
Real-time monitoring of surface-confined platelet activation on TiO2
- 2014
-
Ingår i: Colloids and Surfaces B: Biointerfaces. - : Elsevier BV. - 0927-7765 .- 1873-4367. ; 116, s. 446-451
-
Tidskriftsartikel (refereegranskat)abstract
- For the development of advanced hemocompatible biomaterial functions, there is an unmet demand for in vitro evaluation techniques addressing platelet-surface interactions. We show that the quartz crystal microbalance with dissipation (QCM-D) monitoring technique, here combined with light microscopy, provides a surface sensitive technique that allows for real-time monitoring of the activation and aggregation of the surface-confined platelets on TiO2. The QCM-D signal monitored during adhesion and activation of platelets on TiO2 coated surfaces was found to be different in platelet-poor and platelet-rich environment although light microscopy images taken for each of the two cases looked essentially the same. Interestingly, aggregation of activated platelets was only observed in a protein-rich environment. Our results show that a layer of plasma proteins between the TiO2 surface and the platelets strongly influences the coupling between the platelets and the underlying substrate, explaining both the observed QCM-D signals and the ability of the platelets to aggregate. © 2014 The Authors.
|
|
| 20. |
- Minthon, Lennart, et al.
(författare)
-
The apolipoprotein E epsilon4 allele frequency is normal in fronto-temporal dementia, but correlates with age at onset of disease
- 1997
-
Ingår i: Neuroscience Letters. - 0304-3940. ; 226:1, s. 65-68
-
Tidskriftsartikel (refereegranskat)abstract
- The apolipoprotein (apoE) epsilon4 allele was studied in fronto-temporal dementia (FTD), a diagnostic category including the specific disorders Pick's disease and frontal lobe degeneration of non-Alzheimer type (FLD). These dementing diseases have neuronal and synaptic degeneration in common with Alzheimer's disease (AD), for which the presence of the apoE epsilon4 allele is a known risk factor, and lowers the age of onset of disease. Previous studies on the apoE epsilon4 allele frequency in FTD have been inconclusive. The structural hallmarks of AD, allegedly linked to apoE presentation, neuritic plaques (NP), primarily composed of aggregates of beta-amyloid, and neurofibrillary tangles (NFT), primarily composed of hyperphosphorylated tau, are lacking in FTD. However, tau-positive cytoskeletal pathology is found in Pick's disease, but not in FLD. Resolving whether the epsilon4 frequency is increased in FTD or not may thus give clues to the pathogenetic mechanism of apoE in AD. We therefore studied apoE alleles in a well characterized material of FTD patients. The epsilon4 allele frequency was similar in 25 patients with FTD (14.0%) as compared with 26 healthy controls (13.5%). A post-mortem neuropathological examination was performed in 10 cases (nine had FLD and one Pick's disease). Our finding of a normal epsilon4 allele frequency in our group of FTD, principally consisting of FLD cases, support hypotheses involving differential binding of apoE to beta-amyloid and/or tau, in the development of beta-amyloid deposition and NP formation and/or tau hyperphosphorylation and NFT formation, for the pathogenetic role of apoE in AD. The age at onset was significantly lower (P < 0.01) in FTD patients possessing the epsilon4 allele (48.7 +/- 8.0 years) than in patients not possessing this allele (58.9 +/- 7.6 years). We conclude that, although the apoE epsilon4 allele frequency is not increase in FTD, the epsilon4 allele is not an etiological factor, but may rather be an accelerating factor in the degenerative process of FTD, thereby resulting in an earlier presentation of the disorder in individuals predisposed to develop FTD.
|
|
| 21. |
- Nilsson, Anders K., 1982, et al.
(författare)
-
The proteome signature of cord blood plasma with high hematopoietic stem and progenitor cell count
- 2022
-
Ingår i: Stem Cell Research. - : Elsevier BV. - 1873-5061. ; 61
-
Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem and progenitor cells (HSPC) from umbilical cord blood (UCB) are used for transplantation to treat blood disorders. Methods to estimate the HSPC count in umbilical cord blood, and thereby identify high-value blood units, are time-consuming and costly. Recent studies indicate that the UCB plasma protein composition relates to the HSPC count. We compared the plasma proteome of UCB with high vs low HSPC cell count (> 115 x 10(6) vs < 51 x 10(6) CD34(+) cells l(-1)) by using a combination of global untargeted MS quantitative proteomics and targeted proximity extension assay (PEA) proteomics. For the MS platform, 96 proteins differed significantly between the CD34(+) groups, and out of these, 44 proteins showed more than a two-fold difference. Seven pathways were enriched in high CD34(+) samples, including pathways relating to platelets, coagulation, and lipid transport. For the PEA platform, 61 proteins were differentially abundant, and among these 7 proteins showed more than a two-fold difference between groups. In the PEA data, a high CD34(+) cell count was associated with a protein hub with functions in platelet degranulation. We conclude that the HSPC count is related to the UCB plasma proteome, but that further studies are needed to discern if these findings reflect causal relationships.
|
|
| 22. |
- Nilsson, Jonas, 1970, et al.
(författare)
-
Enrichment of glycopeptides for glycan structure and attachment site identification.
- 2009
-
Ingår i: Nature methods. - : Springer Science and Business Media LLC. - 1548-7105 .- 1548-7091. ; 6:11, s. 809-11
-
Tidskriftsartikel (refereegranskat)abstract
- We present a method to enrich for glycoproteins from proteomic samples. Sialylated glycoproteins were selectively periodate-oxidized, captured on hydrazide beads, trypsinized and released by acid hydrolysis of sialic acid glycosidic bonds. Mass spectrometric fragment analysis allowed identification of glycan structures, and additional fragmentation of deglycosylated ions yielded peptide sequence information, which allowed glycan attachment site and protein identification. We identified 36 N-linked and 44 O-linked glycosylation sites on glycoproteins from human cerebrospinal fluid.
|
|
| 23. |
- Osborn, D. P. S., et al.
(författare)
-
Autosomal recessive cardiomyopathy and sudden cardiac death associated with variants in MYL3
- 2021
-
Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600 .- 1530-0366. ; 23:4, s. 787-792
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose Variants in genes encoding sarcomeric proteins are the most common cause of inherited cardiomyopathies. However, the underlying genetic cause remains unknown in many cases. We used exome sequencing to reveal the genetic etiology in patients with recessive familial cardiomyopathy. Methods Exome sequencing was carried out in three consanguineous families. Functional assessment of the variants was performed. Results Affected individuals presented with hypertrophic or dilated cardiomyopathy of variable severity from infantile- to early adulthood-onset and sudden cardiac death. We identified a homozygous missense substitution (c.170C>A, p.[Ala57Asp]), a homozygous translation stop codon variant (c.106G>T, p.[Glu36Ter]), and a presumable homozygous essential splice acceptor variant (c.482-1G>A, predicted to result in skipping of exon 5). Morpholino knockdown of the MYL3 orthologue in zebrafish, cmlc1, resulted in compromised cardiac function, which could not be rescued by reintroduction of MYL3 carrying either the nonsense c.106G>T or the missense c.170C>A variants. Minigene assay of the c.482-1G>A variant indicated a splicing defect likely resulting in disruption of the EF-hand Ca2+ binding domains. Conclusions Our data demonstrate that homozygous MYL3 loss-of-function variants can cause of recessive cardiomyopathy and occurrence of sudden cardiac death, most likely due to impaired or loss of myosin essential light chain function.
|
|
| 24. |
- Rubino, Domenica, et al.
(författare)
-
Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial
- 2021
-
Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 325:14, s. 1414-1425
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown. OBJECTIVE To compare continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for weight maintenance (both with lifestyle intervention) in adults with overweight or obesity after a 20-week run-in with subcutaneous semaglutide titrated to 2.4 mg weekly. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, 68-week phase 3a withdrawal study conducted at 73 sites in 10 countries from June 2018 to March 2020 in adults with body mass index of at least 30 (or 7 , -27 with >1 weight-related comorbidity) and without diabetes. INTERVENTIONS A total of 902 participants received once-weekly subcutaneous semaglutide during run-in. After 20 weeks (16 weeks of dose escalation; 4 weeks of maintenance dose), 803 participants (89.0%) who reached the 2.4-mg/wk semaglutide maintenance dose were randomized (2:1) to 48 weeks of continued subcutaneous semaglutide (n = 535) or switched to placebo (n = 268), plus lifestyle intervention in both groups. MAIN OUTCOMES AND MEASURES The primary end point was percent change in body weight from week 20 to week 68; confirmatory secondary end points were changes in waist circumference, systolic blood pressure, and physical functioning (assessed using the Short Form 36 Version 2 Health Survey, Acute Version [SF-36]). RESULTS Among 803 study participants who completed the 20-week run-in period (with a mean weight loss of 10.6%) and were randomized (mean age, 46 [SD, 12] years; 634 [79%] women; mean body weight, 107.2 kg [SD, 22.7 kg]), 787 participants (98.0%) completed the trial and 741(92.3%) completed treatment. With continued semaglutide, mean body weight change from week 20 to week 68 was -7.9% vs +6.9% with the switch to placebo (difference, -14.8 [95% CI, -16.0 to -13.5] percentage points; P < .001). Waist circumference (-9.7 cm [95% CI, -10.9 to -8.5 cm]), systolic blood pressure (-3.9 mm Hg [95% CI, -5.8 to -2.0 mm Hg]), and SF-36 physical functioning score (2.5 [95% CI, 1.6-3,3]) also improved with continued subcutaneous semaglutide vs placebo (all P < .001). Gastrointestinal events were reported in 49.1% of participants who continued subcutaneous semaglutide vs 26.1% with placebo; similar proportions discontinued treatment because of adverse events with continued semaglutide (2.4%) and placebo (2.2%). CONCLUSIONS AND RELEVANCE Among adults with overweight or obesity who completed a 20-week run-in period with subcutaneous semaglutide, 2.4 mg once weekly, maintaining treatment with semaglutide compared with switching to placebo resulted in continued weight loss over the following 48 weeks.
|
|
| 25. |
- Santos, Licínia, et al.
(författare)
-
Characterization of sheep erythrocyte glycosphingolipids recognized by human anti-Forssman antibodies.
- 2020
-
Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423. ; 30:11, s. 881-894
-
Tidskriftsartikel (refereegranskat)abstract
- The FORS histo-blood group system is the most recently discovered carbohydrate-based human blood group system. FORS is a rare blood group system, and most individuals have naturally occurring anti-FORS1 antibodies in plasma. Screening for anti-FORS1 antibodies is often done by hemagglutination assays using FORS1-expressing sheep erythrocytes, since FORS1-positive human erythrocytes are most often not available. Here, we have characterized the non-acid glycosphingolipids from sheep erythrocytes and isolated subfractions, with mass spectrometry, binding of antibodies and lectins, and by enzymatic hydrolysis. This demonstrated the presence of Forssman and Galili pentaosylceramides, and a Galili heptaosylceramide. Two complex glycosphingolipids recognized by human anti-FORS1 antibodies were characterized as a Forssman neolacto hybrid hexaosylceramide (GalNAcα3GalNAcβ3Galβ4GlcNAcβ3Galβ4Glcβ1Cer) and a Forssman Galili hybrid heptaosylceramide (GalNAcα3GalNAcβ3Galα3Galβ4GlcNAcβ3Galβ4Glcβ1Cer). These are novel glycosphingolipid structures, and to our knowledge, the first case of an elongated Galili antigen. Thus, the anti-Forssman antibodies in human serum bind not only to the classical Forssman pentaosylceramide (GalNAcα3GalNAcβ3Galα4Galβ4Glcβ1Cer), but also when the GalNAcα3GalNAcβ3 sequence is presented on a neolacto core chain and even on a Galili carbohydrate sequence.
|
|
