| 1. |
- Brinck, Jonas W., et al.
(författare)
-
High-density lipoprotein from end-stage renal disease patients exhibits superior cardioprotection and increase in sphingosine-1-phosphate
- 2018
-
Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 48:2
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic kidney disease (CKD) exacerbates the risk of death due to cardiovascular disease (CVD). Modifications to blood lipid metabolism which manifest as increases in circulating triglycerides and reductions in high-density lipoprotein (HDL) cholesterol are thought to contribute to increased risk. In CKD patients, higher HDL cholesterol levels were not associated with reduced mortality risk. Recent research has revealed numerous mechanisms by which HDL could favourably influence CVD risk. In this study, we compared plasma levels of sphingosine-1-phosphate (S1P), HDL-associated S1P (HDL-S1P) and HDL-mediated protection against oxidative stress between CKD and control patients. Methods: High-density lipoprotein was individually isolated from 20 CKD patients and 20 controls. Plasma S1P, apolipoprotein M (apoM) concentrations, HDL-S1P content and the capacity of HDL to protect cardiomyocytes against doxorubicin-induced oxidative stress in vitro were measured. Results: Chronic kidney disease patients showed a typical profile with significant reductions in plasma HDL cholesterol and albumin and an increase in triglycerides and pro-inflammatory cytokines (TNF-alpha and IL-6). Unexpectedly, HDL-S1P content (P = .001) and HDL cardioprotective capacity (P = .034) were increased significantly in CKD patients. Linear regression analysis of which factors could influence HDL-S1P content showed an independent, negative and positive association with plasma albumin and apoM levels, respectively. Discussion: The novel and unexpected observation in this study is that uremic HDL is more effective than control HDL for protecting cardiomyocytes against oxidative stress. It is explained by its higher S1P content which we previously demonstrated to be the determinant of HDL-mediated cardioprotective capacity. Interestingly, lower concentrations of albumin in CKD are associated with higher HDL-S1P.
|
|
| 2. |
- Chirinos, Julio A., et al.
(författare)
-
Reduced Apolipoprotein M and Adverse Outcomes across the Spectrum of Human Heart Failure
- 2020
-
Ingår i: Circulation. - 0009-7322. ; , s. 1463-1476
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Apo (apolipoprotein) M mediates the physical interaction between high-density lipoprotein (HDL) particles and sphingosine-1-phosphate (S1P). Apo M exerts anti-inflammatory and cardioprotective effects in animal models. Methods: In a subset of PHFS (Penn Heart Failure Study) participants (n=297), we measured apo M by Enzyme-Linked ImmunoSorbent Assay (ELISA). We also measured total S1P by liquid chromatography-mass spectrometry and isolated HDL particles to test the association between apo M and HDL-associated S1P. We confirmed the relationship between apo M and outcomes using modified aptamer-based apo M measurements among 2170 adults in the PHFS and 2 independent cohorts: the Washington University Heart Failure Registry (n=173) and a subset of TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial; n=218). Last, we examined the relationship between apo M and ≈5000 other proteins (SomaScan assay) to identify biological pathways associated with apo M in heart failure. Results: In the PHFS, apo M was inversely associated with the risk of death (standardized hazard ratio, 0.56 [95% CI, 0.51-0.61]; P<0.0001) and the composite of death/ventricular assist device implantation/heart transplantation (standardized hazard ratio, 0.62 [95% CI, 0.58-0.67]; P<0.0001). This relationship was independent of HDL cholesterol or apo AI levels. Apo M remained associated with death (hazard ratio, 0.78 [95% CI, 0.69-0.88]; P<0.0001) and the composite of death/ventricular assist device/heart transplantation (hazard ratio, 0.85 [95% CI, 0.76-0.94]; P=0.001) in models that adjusted for multiple confounders. This association was present in both heart failure with reduced and preserved ejection fraction and was replicated in the Washington University cohort and a cohort with heart failure with preserved ejection fraction only (TOPCAT). The S1P and apo M content of isolated HDL particles strongly correlated (R=0.81, P<0.0001). The top canonical pathways associated with apo M were inflammation (negative association), the coagulation system (negative association), and liver X receptor/retinoid X receptor activation (positive association). The relationship with inflammation was validated with multiple inflammatory markers measured with independent assays. Conclusions: Reduced circulating apo M is independently associated with adverse outcomes across the spectrum of human heart failure. Further research is needed to assess whether the apo M/S1P axis is a suitable therapeutic target in heart failure.
|
|
| 3. |
|
|
| 4. |
- Collin, Åsa, et al.
(författare)
-
Total mesorectal excision quality in rectal cancer surgery affects local recurrence rate but not distant recurrence and survival : population-based cohort study
- 2024
-
Ingår i: BJS Open. - : Oxford University Press. - 2474-9842. ; 8:4
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe quality of the total mesorectal excision specimen in rectal cancer surgery is assessed with a three-tier grade (mesorectal, intramesorectal and muscularis propria). This study aimed to analyse the prognostic impact of the total mesorectal excision grade on survival, and to identify risk factors for intramesorectal and muscularis propria resection in a population-based setting.MethodsAll patients in the Swedish Colorectal Cancer Registry with rectal cancer stage I–III ≤ 10 cm from the anal verge, diagnosed 2015–2019, undergoing total mesorectal excision were analysed. Clinical, surgical and pathological data were retrieved and analysed for the following primary outcomes: local and distant recurrence and overall and relative survival; secondary outcomes were risk factors for total mesorectal excision grading (intramesorectal or muscularis propria resection). Of note, postoperative death < 30 days or recurrence within 90 days were exclusion criteria for survival and recurrence analysis. Recurrence-free patients with less than 3 years follow-up, and patients lacking data regarding recurrence, were also excluded from recurrence analyses.ResultsOverall, of 7979 patients treated during the study interval, 1499 patients were eligible for recurrence, 2441 patients for survival and 2476 patients for risk-factor analyses, of which 75% were graded mesorectal, 17% intramesorectal and 8% muscularis propria. Median follow-up for survival was 42 (1–77) months. The worst total mesorectal excision grading (muscularis propria resection) was an independent risk factor for local recurrence in multivariable analysis (HR 2.73, 95% c.i. 1.07 to 7.0, P = 0.036). Total mesorectal excision grade had no impact on distant recurrence or survival. Female sex, tumour level <5 cm, abdominoperineal resection, minimally invasive surgery (laparoscopic and robotic), high blood loss, long duration of surgery and intraoperative perforation were independent risk factors for worse total mesorectal excision grading (intramesorectal and/or muscularis propria resection) in multivariable analyses.ConclusionMuscularis propria resection increases the risk of local recurrence but does not seem to affect distant recurrence or survival.
|
|
| 5. |
- Cukalevski, Risto, et al.
(författare)
-
Structural Changes in Apolipoproteins Bound to Nanoparticles
- 2011
-
Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 27:23, s. 14360-14369
-
Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles are widely used in the pharmaceutical and food industries, but the consequences of exposure to the human body have not been thoroughly investigated. Apolipoprotein A-I (apoAI), the major protein in high-density lipoprotein (HDL), and other lipoproteins are found in the corona around many nanopartides, but data on protein structural and functional effects are lacking. Here we investigate the structural consequences of the adsorption of apoAI, apolipoprotein B100 (apoB100), and HDL on polystyrene nanoparticles with different surface charges. The results of circular dichroism, fluorescence spectroscopy, and limited proteolysis experiments indicate effects on both secondary and tertiary structures. Plain and negatively charged nanoparticles induce helical structure in apoAI (negative net charge) whereas positively charged nanoparticles reduce the amount of helical structure. Plain and negatively charged partides induce a small blue shift in the tryptophan fluorescence spectrum, which is not noticed with the positively charged particles. Similar results are observed with reconstituted HDL. In apoB100, both secondary and tertiary structures are perturbed by all particles. To investigate the generality of the role of surface charge, parallel experiments were performed using human Serum albumin (HSA, negative net charge) and lysozyme (positive net charge). Again, the secondary structure is most affected by nanoparticles carrying an opposite surface charge relative to the protein. Nanoparticles carrying the same net charge as the protein induce only minor structural changes in lysozyme whereas a moderate change is observed for HSA. Thus, surface charge is a critical parameter for predicting structural changes in adsorbed proteins, yet the effect is specific for each protein.
|
|
| 6. |
- Dahlbäck, Cecilia, et al.
(författare)
-
Accuracy of magnetic resonance imaging staging of tumour and nodal stage in rectal cancer treated by primary surgery : a population-based study
- 2022
-
Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 24:9, s. 1047-1053
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: The preoperative stage of rectal cancer is an important prognostic factor affecting treatment recommendations. Currently, magnetic resonance imaging (MRI) is used for clinical staging to identify patients who should be recommended for neoadjuvant oncological treatment. The aim of this work was to investigate the accuracy of the preoperative T- and N-stage and also involvement of the mesorectal fascia (MRF) as determined by MRI in a Swedish national cohort. Method: Patients who had undergone resectional surgery for rectal cancer without neoadjuvant treatment in Sweden in the period 2013–2017 were identified through the Swedish Colorectal Cancer Registry (n = 2062). The T- and N-stage determined by preoperative MRI were compared with the histopathological results. The MRI-assessed MRF status was compared with the circumferential resection margin. Results: Sensitivity for differentiating T1-2 from T3-4 was 69% and specificity 77%. Sensitivity to detect N1-2 was 42% and specificity 81%. Sensitivity for MRF positivity was 50% and specificity 92%. Agreement analysed by weighted kappa analysis was 0.47 for T-stage [confidence interval (CI) 0.44–0.51], 0.24 for N-stage (CI 0.19–0.24) and 0.20 for MRF status (CI 0.12–0.29). Conclusion: In this study, accuracy of the preoperative MRI was lower than expected for rectal cancers. Overstaging might lead to potentially harmful neoadjuvant treatment and understaging can lead to a higher risk of tumour recurrence. The results of this study show that efforts should be made to increase the accuracy of the preoperative evaluation in order to optimize treatment recommendations.
|
|
| 7. |
- Dahlbäck, Cecilia, et al.
(författare)
-
Aesthetic result after breast-conserving therapy is associated with quality of life several years after treatment. Swedish women evaluated with BCCT.core and BREAST-Q (TM)
- 2017
-
Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 164:3, s. 679-687
-
Tidskriftsartikel (refereegranskat)abstract
- A gold standard for evaluation of aesthetic outcome after breast-conserving therapy (BCT) is still lacking. The BCCT.core software has been developed to assess aesthetic result in a standardised way. We aimed to study how the result of BCCT.core after BCT is associated with quality of life, measured with the BREAST-Q (TM), a validated questionnaire. Women eligible for BCT were consecutively recruited between February 1st 2008 and January 31st 2012 (n = 653). Photographs of 310 women, taken one year after BCT, were evaluated using the BCCT.core software. The postoperative BCT module of the BREAST-Q (TM) questionnaire was administered by mail and 348 questionnaires were returned (median 5.5 years after BCT). In all, 216 women had both BCCT.core results and completed BREAST-Q (TM) questionnaires available. The results from the BCCT.core evaluation were: excellent n = 49 (15.8%); good n = 178 (57.4%); fair n = 73 (23.5%); poor n = 10 (3.2%). The median BREAST-Q (TM) score for satisfaction with breasts was 66 [interquartile range (IQR) 57-80] and for psychosocial well-being 82 (IQR 61-100). Poor/fair results on BCCT.core were associated with Q-scores below median for both satisfaction with breasts [odds ratio (OR) 3.4 (confidence interval (CI) 1.7-6.8)] as well as for psychosocial well-being [OR 2.2 (CI 1.1-4.2)]. A statistically significant association between BCCT.core results one year after BCT and quality of life ratings using BREAST-Q (TM) several years later is shown in this study. This implies that the BCCT.core may be valuable in BCT follow-up and used as a standardised instrument in the evaluation of aesthetic results.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Dahlbäck, Cecilia, et al.
(författare)
-
Long-term outcome of lymph vessel transplantation after chronic lymphorrhea
- 2021
-
Ingår i: Case Reports in Plastic Surgery and Hand Surgery. - : Informa UK Limited. - 2332-0885. ; 8:1, s. 169-174
-
Tidskriftsartikel (refereegranskat)abstract
- A 52-year-old male patient developed a chronic fistula with excessive lymph leakage in the left axilla following removal of an enlarged lymph node with chronic local adipose tissue inflammation due to infection. After multiple surgeries, treatment with lymphatic vessel transplantation was successful. No recurrence occurred over 20 years of follow-up.
|
|
| 11. |
- Dahlbäck, Cecilia, et al.
(författare)
-
Muscle mass and quality as predictors for complications, recurrence and length of hospital stay in acute uncomplicated diverticulitis: a retrospective cohort study
- 2023
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 58:4, s. 375-379
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThe aim of this study was to investigate the potential correlation between muscle mass/muscle quality and risk of complications or recurrence in patients presenting with acute uncomplicated diverticulitis. It was also to study if low muscle mass/quality correlated to prolonged hospital stay.Materials and methodsThe study population comprised 501 patients admitted to Helsingborg Hospital or Skåne University Hospital between 1 January 2015 and 31 December 2017, who had been diagnosed with acute uncomplicated diverticulitis and undergone computed tomography upon admission. The scans were used to estimate skeletal muscle mass and muscle radiation attenuation (an indicator for muscle quality). Skeletal muscle index was obtained by adjusting skeletal muscle mass to the patients’ height. Values of below the fifth percentile of a normal population were considered low.ResultsThere were no differences between the patients with normal versus those with low skeletal muscle mass, skeletal muscle index or muscle radiation attenuation regarding risk of complications or recurrence of diverticular disease. However, as only 11 patients had complications, no conclusion as to a potential correlation can be made. Low muscle quality correlated to longer hospital stay, also when adjusting for other potential confounders.ConclusionsMuscle mass/quality do not seem to serve as predictor of risk for recurrent disease in patients with acute uncomplicated diverticulitis. However, low muscle radiation attenuation was associated with prolonged hospital stay. This indicates that muscle quality, assessed by computed tomography scan, might be used in clinical practise to identify patients at risk of longer hospitalisation.
|
|
| 12. |
- DAHLBÄCK, CECILIA, et al.
(författare)
-
Patients Undergoing Breast-Conserving Surgery Can Benefit from the Opportunity to Participate in Choosing Their Surgical Technique
- 2017
-
Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 41:3, s. 734-741
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Shared decision-making is increasingly advocated in many countries. The aims of this study were to investigate whether patients receiving breast-conserving surgery at Skåne University Hospital Malmö, Sweden, perceived an offered possibility to join in the decision-making process regarding the surgical method; to identify potential determinants for not having perceived such an offer; and to study how this perception of being offered an opportunity to take part in the decision-making process affected satisfaction with the aesthetic outcome. Methods: Women offered breast-conserving surgery were consecutively recruited over a period of 4 years. In all, 324 women completed a study-specific questionnaire. Results: A majority of the women (53 %) perceived that they had not, or had only partly, been offered a possibility to take part in the decision-making process. Patients who reported that they had received enough preoperative information regarding the expected aesthetic result were more likely to have perceived such an offer (odds ratio (OR) 5.44; confidence interval (CI) 2.83–10.43). Women who had perceived an opportunity to be involved were more satisfied with the aesthetic result (OR 2.71; CI 1.18–6.25) and more likely to have had their expectations met regarding the aesthetic result (OR 5.91; CI 2.01–17.38). Conclusion: When deciding on a suitable surgical approach for women with early breast cancer, physicians could try to more clearly communicate to the women that they can choose whether or not to participate in the decision-making regarding surgical technique. This might improve satisfaction. An important part of patient involvement is sufficient preoperative information.
|
|
| 13. |
- Delveus, Hugo, et al.
(författare)
-
Diverticulosis and risk of diverticulitis in 10 years; a Swedish retrospective observational study
-
Ingår i: Scandinavian Journal of Gastroenterology. - 0036-5521.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Diverticulosis is a common condition and is thought to be increasing in the Western population. Several studies have attempted to estimate the prevalence of diverticulosis and it’s inflamed state, diverticulitis, with results varying depending on study population and methodology, The aim of this study was to investigate the prevalence of diverticulosis in patients undergoing colonoscopy at a Swedish academic referral centre and to study the incidence of diverticulitis in a 10-year follow-up. Methods: All patients who had undergone colonoscopy at the Endoscopy unit, Skåne University Hospital, Sweden, during 01 January 2010 through 31 December 2011 were identified. The colonoscopy referrals, colonoscopy reports, and medical records until 14 June 2022 were reviewed. Results: In all, 2648 patients were included in the study, whereof 910 patients had reported diverticulosis (34.4%). During the 10-year follow-up, the overall incidence of computed tomography verified diverticulitis was 4.4%, and 0.6% for patients with and without diverticulosis at index colonoscopy, respectively. Of the 50 patients that developed diverticulitis, 21 were complicated and 29 uncomplicated Conclusion: Diverticulosis is a common condition in the population, although most patients will not develop diverticulitis.
|
|
| 14. |
- Ferreira, Silvia A., et al.
(författare)
-
Biocompatibility of mannan nanogel-safe interaction with plasma proteins
- 2012
-
Ingår i: Biochimica et Biophysica Acta. General Subjects. - : Elsevier BV. - 0304-4165. ; 1820:7, s. 1043-1051
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Self-assembled mannan nanogels are designed to provide a therapeutic or vaccine delivery platform based on the bioactive properties of mannan to target mannose receptor expressed on the surface of antigen-presenting cells, combined with the performance of nanogels as carriers of biologically active agents. Methods: Proteins in the corona around mannan nanogel formed in human plasma were identified by mass spectrometry after size exclusion chromatography or centrifugation followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Structural changes and time dependent binding of human apolipoprotein A-I (apoA-I) and human serum albumin (HSA) to mannan nanogel were studied using intrinsic tryptophan fluorescence and circular dichroism spectroscopy. The mannan nanogel effect on blood coagulation and fibrillation of Alzheimer's disease-associated amyloid beta peptide and hemodialysis-associated amyloidosis beta 2 microglobulin was evaluated using thrombin generation assay or thioflavin T fluorescence assay, respectively. Results: The protein corona around mannan nanogel is formed through a slow process, is quite specific comprising apolipoproteins B-100, A-I and E and HSA, evolves over time, and the equilibrium is reached after hours to days. Structural changes and time dependent binding of apoA-I and HSA to mannan nanogel are minor. The mannan nanogel does not affect blood coagulation and retards the fibril formation. Conclusions: Mannan nanogel has a high biosafety and biocompatibility, which is mandatory for nanomaterials to be used in biomedical applications. General Significance: Our research provides a molecular approach to evaluate the safety aspects of nanomaterials, which is of general concern in society and science. (C) 2012 Elsevier B.V. All rights reserved.
|
|
| 15. |
- Frej, Cecilia, et al.
(författare)
-
A Shift in ApoM/S1P between HDL-Particles in Women with Type 1 Diabetes Mellitus Is Associated with Impaired Anti-Inflammatory Effects of the ApoM/S1P Complex
- 2017
-
Ingår i: Arteriosclerosis, Thrombosis, and Vascular Biology. - 1079-5642. ; 37:6, s. 1194-1205
-
Tidskriftsartikel (refereegranskat)abstract
- Objective-Type 1 diabetes mellitus (T1D) patients have an increased risk of cardiovascular disease despite high levels of high-density lipoproteins (HDL). Apolipoprotein M (apoM) and its ligand sphingosine 1-phospate (S1P) exert many of the anti-inflammatory effects of HDL. We investigated whether apoM and S1P are altered in T1D and whether apoM and S1P are important for HDL functionality in T1D. Approach and Results-ApoM and S1P were quantified in plasma from 42 healthy controls and 89 T1D patients. HDL was isolated from plasma and separated into dense, medium-dense, and light HDL by ultracentrifugation. Primary human aortic endothelial cells were challenged with tumor necrosis factor-α in the presence or absence of isolated HDL. Proinflammatory adhesion molecules E-selectin and vascular cellular adhesion molecule-1 were quantified by flow cytometry. Activation of the S1P1-receptor was evaluated by analyzing downstream signaling targets and receptor internalization. There were no differences in plasma levels of apoM and S1P between controls and T1D patients, but the apoM/S1P complexes were shifted from dense to light HDL particles in T1D. ApoM/S1P in light HDL particles from women were less efficient in inhibiting expression of vascular cellular adhesion molecule-1 than apoM/S1P in denser particles. The light HDL particles were unable to activate Akt, whereas all HDL subfractions were equally efficient in activating Erk and receptor internalization. Conclusions-ApoM/S1P in light HDL particles were inefficient in inhibiting tumor necrosis factor-α-induced vascular cellular adhesion molecule-1 expression in contrast to apoM/S1P in denser HDL particles. T1D patients have a higher proportion of light particles and hence more dysfunctional HDL, which could contribute to the increased cardiovascular disease risk associated with T1D.
|
|
| 16. |
- Frej, Cecilia, et al.
(författare)
-
Quantification of sphingosine 1-phosphate by validated LC-MS/MS method revealing strong correlation with apolipoprotein M in plasma but not in serum due to platelet activation during blood coagulation.
- 2015
-
Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 407:28, s. 8533-8542
-
Tidskriftsartikel (refereegranskat)abstract
- Sphingosine 1-phosphate (S1P) is a signalling sphingolipid affecting multiple cellular functions of vascular and immune systems. It circulates at submicromolar levels bound to HDL-associated apolipoprotein M (apoM) or to albumin. S1P in blood is mainly produced by platelets and erythrocytes, making blood sampling for S1P quantification delicate. Standardisation of sampling is thereby of great importance to obtain robust data. By optimising and characterising the extraction procedure and the LC-MS/MS analysis, we have developed and validated a highly specific and sensitive method for S1P quantification. Blood was collected from healthy individuals (n = 15) to evaluate the effects of differential blood sampling on S1P levels. To evaluate correlation between S1P and apoM in different types of plasma and serum, apoM was measured by ELISA. The method showed good accuracy and precision in the range of 0.011 to 0.9 μM with less than 0.07 % carryover. We found that the methanol precipitation used to extract S1P co-extracted apoM and several other HDL-proteins from plasma. The platelet-associated S1P was released during coagulation, thus increasing the S1P concentration to double in serum as compared to that in plasma. Gel filtration chromatography revealed that the platelet-released S1P was mainly bound to albumin. This explains why the strong correlation between S1P and apoM levels in plasma is lost upon the clotting process and hence not observed in serum. We have developed, characterised and validated an efficient, highly sensitive and specific method for the quantification of S1P in biological material.
|
|
| 17. |
- Frej, Cecilia, et al.
(författare)
-
Sphingosine 1-phosphate and its carrier apolipoprotein M in human sepsis and in Escherichia coli sepsis in baboons
- 2016
-
Ingår i: Journal of Cellular and Molecular Medicine. - : Wiley. - 1582-1838 .- 1582-4934. ; 20:6, s. 1170-1181
-
Tidskriftsartikel (refereegranskat)abstract
- Sphingosine 1-phosphate (S1P) is an important regulator of vascular integrity and immune cell migration, carried in plasma by high-density lipoprotein (HDL)-associated apolipoprotein M (apoM) and by albumin. In sepsis, the protein and lipid composition of HDL changes dramatically. The aim of this study was to evaluate changes in S1P and its carrier protein apoM during sepsis. For this purpose, plasma samples from both human sepsis patients and from an experimental Escherichia coli sepsis model in baboons were used. In the human sepsis cohort, previously studied for apoM, plasma demonstrated disease-severity correlated decreased S1P levels, the profile mimicking that of plasma apoM. In the baboons, a similar disease-severity dependent decrease in plasma levels of S1P and apoM was observed. In the lethal E. coli baboon sepsis, S1P decreased already within 6-8 hrs, whereas the apoM decrease was seen later at 12-24 hrs. Gel filtration chromatography of plasma from severe human or baboon sepsis on Superose 6 demonstrated an almost complete loss of S1P and apoM in the HDL fractions. S1P plasma concentrations correlated with the platelet count but not with erythrocytes or white blood cells. The liver mRNA levels of apoM and apoA1 decreased strongly upon sepsis induction and after 12 hr both were almost completely lost. In conclusion, during septic challenge, the plasma levels of S1P drop to very low levels. Moreover, the liver synthesis of apoM decreases severely and the plasma levels of apoM are reduced. Possibly, the decrease in S1P contributes to the decreased endothelial barrier function observed in sepsis.
|
|
| 18. |
- Gardfjell, Anna, et al.
(författare)
-
Patient satisfaction after unilateral oncoplastic volume displacement surgery for breast cancer, evaluated with the BREAST-Q™
- 2019
-
Ingår i: World Journal of Surgical Oncology. - : Springer Science and Business Media LLC. - 1477-7819. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Oncoplastic breast-conserving surgery allows larger resections in unfavorable locations, with an improved chance of preserving esthetics. Indications and timing for potential contralateral surgery to obtain symmetry are not clear. The aim of this study was to evaluate patient satisfaction after unilateral oncoplastic volume displacement surgery, to investigate potential risk factors for lower patient satisfaction and to assess patient wish for contralateral surgery. Method: A cohort of 144 women, consecutively treated for breast cancer with unilateral breast-conserving oncoplastic volume displacement surgery, followed by radiotherapy and with an unoperated contralateral breast, was sent the BREAST-Q™ breast-conserving therapy (BCT) and a study-specific questionnaire. In all, 120 women (83%) responded. For these women, the median value for resected specimen weight was 92 g (range 14-345) and for the estimated percentage of the breast volume excised 15% (range 3-35%). Results: The median patient-reported score for "Satisfaction with breast" (BREAST-Q™ BCT) was 74/100. Factors associated with a score below median value in a simple logistic regression model adjusted for age and BMI were axillary clearance (OR 2.46, 95% CI 1.09-5.56), neoadjuvant chemotherapy (OR 3.26, 95% CI 1.15-9.24), and low breast density (OR 2.32 95% CI 1.02-5.29). Thirteen women (11%) were interested in contralateral surgery. Conclusion: Most patients in this study cohort, who had undergone breast-conserving therapy with oncoplastic volume displacement techniques, were satisfied with their breasts without surgery to the contralateral breast. This indicates that contralateral surgery to achieve symmetry only should be performed after individual evaluation and as a delayed procedure.
|
|
| 19. |
|
|
| 20. |
- Hafizi, Sassan, et al.
(författare)
-
Tensin2 reduces intracellular phosphatidylinositol 3,4,5-trisphosphate levels at the plasma membrane
- 2010
-
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 399:3, s. 396-401
-
Tidskriftsartikel (refereegranskat)abstract
- Tensins are proposed cytoskeleton-regulating proteins. However, Tensin2 additionally inhibits Akt signalling and cell survival. Structural modelling of the Tensin2 phosphatase (PTPase) domain revealed an active site-like pocket receptive towards phosphoinositides. Tensin2-expressing HEK293 cells displayed negligible levels of plasma membrane phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P-3) under confocal microscopy. However, mock-transfected cells, and Tensin2 cells harbouring a putative phosphatase-inactivating mutation, exhibited significant PtdIns(3,4,5)P-3 levels, which decreased upon phosphatidylinositol 3-kinase inhibition with LY294002. In contrast, wtTensin3, mock and mutant cells were identical in membrane PtdIns(3,4,5)P-3 and Akt phosphorylation. In vitro lipid PTPase activity was however undetectable in isolated recombinant PTPase domains of both Tensins, indicating a possible loss of structural stability when expressed in isolation. In summary, we provide evidence that Tensin2, in addition to regulating cytoskeletal dynamics, influences phosphoinositide-Akt signalling through its PTPase domain.
|
|
| 21. |
- Ihse, Cecilia, 1970-
(författare)
-
Präst, stånd och stat : Kung och kyrka i förhandling 1642-1686
- 2005
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation is the result of a study of power relations between the crown and the church in Sweden during the 17th century. The study is focused on the Swedish Parliament and how the Estate of the Clergy responded to royal pretensions. The Swedish Clerical Estate is viewed as essential for the Swedish state formation process.The argument in the study is inspired by theories suggesting that state building and state formation were outcomes of a bargaining process between rulers and local power holders. The perspective presented by the historian Jan Glete is of great importance. He defines the early modern state as a complex organization providing protection and violence control. He emphasizes that the power of the state and the state’s character were dependent upon how the state could assert power. In order to do this, the rulers bartered with their subjects using protection as a commodity while in return the subjects paid required taxes. This bargaining process is interpreted as interactive. The rulers linked various local interests to the state and in doing so gained control of the society and the use of violence.The Swedish Clerical Estate played an important role in this process. Due in part to this fact, the clergy differed from the other subjects of the realm such as the nobility or the peasants. The clergy did not own any sizeable amount of property and did not exert any economical influence. Instead the Clerical Estate negotiated using their ideological, cultural and political resources. These commodities became essential in how the king organized the state. In exchange for royal protection, the clergy were given the task of supporting and explaining the crown’s economical and military needs. By doing so, the Clerical Estate legitimated the royal power in the parliament and in the society as a whole. At the same time, this negotiation signified a definition of the role of the clergyman within the state. Though the Clerical Estate sometimes tried to reject royal claims, it was the king who decided the conditions of negotiation. The parliament as a political field was created by the king and for the king. From a political point of view, religion and a theological framework became of great importance and were adopted by the crown in order to exploit resources. Taking this into consideration, the 17th century Swedish state seems to be more effective than other European early modern states.
|
|
| 22. |
- Korsbakke, Kevin, et al.
(författare)
-
Tumor and nodal staging of colon cancer : accuracy of preoperative computed tomography at a Swedish high-volume center
- 2019
-
Ingår i: Acta Radiologica Open. - : SAGE Publications. - 2058-4601. ; 8:12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: When deciding treatment options for patients with colon cancer, accurate staging is required. In Sweden, the main preoperative evaluation modality to determine tumor and nodal stage is computed tomography (CT).Purpose: The aim of this study was to investigate how well the preoperative (CT-determined) clinical tumor and nodal stage (cTN) correlated with the postoperative histopathological stage (pTN). Another aim was to validate the tumor and nodal stage data in the Swedish Colorectal Cancer Registry (SCRCR).Material and Methods: The SCRCR was used to identify patients with colon cancer, treated at a Swedish high-volume center during 2013-2016 (n = 974). Data were gathered from medical records regarding cTN and pTN stage, and predefined patient and tumor variables. The agreement between cTN and pTN was analyzed using kappa statistics.Results: After excluding patients with either pre- or postoperative TN stage missing, 383 patients remained for further analyses. The analyses showed an agreement between cT and pT of κ: 0.27 and between cN and pN of κ: 0.21 (fair agreement). When comparing tumors with low (T1-3; N0) versus high risk (T4; N1-2), the kappa value was 0.19 (slight agreement). When comparing the SCRCR to medical records, 78% of completely staged tumors had been correctly reported.Conclusion: The agreement between cTN and pTN was low in this study population, indicating a need for enhanced precision of the preoperative staging process. A high frequency of erroneous preoperative staging data in the SCRCR shows the need for further efforts of ensuring correct data transfers into the registry.
|
|
| 23. |
|
|
| 24. |
- Lundqvist, Martin, et al.
(författare)
-
The nanoparticle protein corona formed in human blood or human blood fractions
- 2017
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
-
Tidskriftsartikel (refereegranskat)abstract
- The protein corona formed around nanoparticles in protein-rich fluids plays an important role for nanoparticle biocompatibility, as found in several studies during the last decade. Biological fluids have complex compositions and the molecular components interact and function together in intricate networks. Therefore, the process to isolate blood or the preparation of blood derivatives may lead to differences in the composition of the identified protein corona around nanoparticles. Here, we show distinct differences in the protein corona formed in whole blood, whole blood with EDTA, plasma, or serum. Furthermore, the ratio between particle surface area to protein concentration influences the detected corona. We also show that the nanoparticle size per se influences the formed protein corona due to curvature effects. These results emphasize the need of investigating the formation and biological importance of the protein corona in the same environment as the nanoparticles are intended for or released into.
|
|
| 25. |
- Martuszewska, Danuta, et al.
(författare)
-
Tensin3 is a negative regulator of cell migration and all four Tensin family members are downregulated in human kidney cancer.
- 2009
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:2
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Tensin family of intracellular proteins (Tensin1, -2, -3 and -4) are thought to act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Dysregulation of Tensin expression has previously been implicated in human cancer. Here, we have for the first time evaluated the significance of all four Tensins in a study of human renal cell carcinoma (RCC), as well as probed the biological function of Tensin3. PRINCIPAL FINDINGS: Expression of Tensin2 and Tensin3 at mRNA and protein levels was largely absent in a panel of diverse human cancer cell lines. Quantitative RT-PCR analysis revealed mRNA expression of all four Tensin genes to be significantly downregulated in human kidney tumors (50-100% reduction versus normal kidney cortex; P<0.001). Furthermore, the mRNA expressions of Tensins mostly correlated positively with each other and negatively with tumor grade, but not tumor size. Immunohistochemical analysis revealed Tensin3 to be present in the cytoplasm of tubular epithelium in normal human kidney sections, whilst expression was weaker or absent in 41% of kidney tumors. A subset of tumor sections showed a preferential plasma membrane expression of Tensin3, which in clear cell RCC patients was correlated with longer survival. Stable expression of Tensin3 in HEK 293 cells markedly inhibited both cell migration and matrix invasion, a function independent of putative phosphatase activity in Tensin3. Conversely, siRNA knockdown of endogenous Tensin3 in human cancer cells significantly increased their migration. CONCLUSIONS: Our findings indicate that the Tensins may represent a novel group of metastasis suppressors in the kidney, the loss of which leads to greater tumor cell motility and consequent metastasis. Moreover, tumorigenesis in the human kidney may be facilitated by a general downregulation of Tensins. Therefore, anti-metastatic therapies may benefit from restoring or preserving Tensin expression in primary tumors.
|
|
| 26. |
|
|
| 27. |
- Munshi, Eihab, et al.
(författare)
-
Long-term Outcomes of Endoscopic Vacuum Therapy and Transanal Drainage for Anastomotic Leakage After Anterior Resection
- 2022
-
Ingår i: In Vivo. - : Anticancer Research USA Inc.. - 0258-851X .- 1791-7549. ; 36:5, s. 2275-2278
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Anastomotic leakage (AL) after anterior resection for rectal cancer occurs in up to 26% of patients. In the last decade, endoscopic vacuum therapy (EVT) has gained interest as a treatment option for AL. This study aimed to compare the clinical success rate of EVT versus transanal drainage (TD) in AL treatment and investigate whether the frequency of bowel continuity differed. Patients and Methods: Patients treated for rectal cancer at the Skåne University Hospital, Sweden between 2009-2018 were identified through the Swedish Colorectal Cancer Registry (SCRCR). Patient characteristics, operative and AL data were retrieved by SCRCR and chart review. Results: Out of 1,095 patients subjected to rectal cancer surgery, 361 patients had undergone anterior resection. AL occurred in 39 patients, of these 14 patients were treated with EVT and 17 with TD. Bowel continuity was achieved in 50% of patients treated with EVT and 65% of patients treated with TD (p=0.28). The patients were under treatment for a median period of 24.5 days (IQR=11-36 days) when treated with EVT and 37 days (IQR=17-51 days) with TD. Conclusion: No superiority of EVT treatment could be shown in restoring bowel continuity. This questions the role of EVT in AL treatment after anterior resection.
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
- Oslakovic, Cecilia, et al.
(författare)
-
Anionic Phospholipids Lose their Procoagulant Properties when Incorporated into High-Density Lipoproteins.
- 2009
-
Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 284:9, s. 5896-5904
-
Tidskriftsartikel (refereegranskat)abstract
- Blood coagulation involves a series of enzymatic protein complexes that assemble on the surface of anionic phospholipid. To investigate whether apolipoproteins affect coagulation reactions, they where included during the preparation of anionic phospholipid vesicles using a detergent solubilization-dialysis method. Apolipoprotein components of high-density lipoproteins, especially apolipoprotein A-I, had pronounced anticoagulant effect. The anionic phospholipids lost their procoagulant effect when the vesicle preparation method was performed in the presence of apolipoprotein A-I. The anionic phospholipid-apolipoprotein A-I particles were 8-10 nm in diameter and contained around 60-80 phospholipid molecules, depending on the phospholipid composition. The phospholipids of these particles were unable to support the activation of prothrombin by factor Xa in the presence of factor Va, and unable to support binding of factor Va, while binding of prothrombin and factor Xa were efficient. Phospholipid transfer protein was shown to mediate transfer of phospholipids from liposomes to apolipoprotein A-I containing reconstituted high-density lipoprotein. In addition, serum was also shown to neutralize the procoagulant effect of anionic liposomes and to efficiently mediate transfer of phospholipids from liposomes to either apolipoprotein A-I or apolipoprotein B containing particles. In conclusion, apolipoprotein A-I was found to neutralize the procoagulant properties of anionic phospholipids by arranging the phospholipids in surface areas that are too small to accommodate the prothrombinase complex. This anionic phospholipid scavenger function may be an important mechanism to control the exposure of such phospholipids to circulating blood and thereby prevent inappropriate stimulation of blood coagulation.
|
|
| 31. |
|
|
| 32. |
- Oslakovic, Cecilia, et al.
(författare)
-
Polystyrene nanoparticles affecting blood coagulation.
- 2012
-
Ingår i: Nanomedicine: Nanotechnology, Biology and Medicine. - : Elsevier BV. - 1549-9642 .- 1549-9634. ; 8:6, s. 981-986
-
Tidskriftsartikel (refereegranskat)abstract
- Association of nanoparticles with blood coagulation proteins may influence the natural balance between pro-and anticoagulant pathways. We investigated whether polystyrene nanoparticles, when added to human plasma, affected the generation of thrombin in plasma. Amine-modified nanoparticles were found to decrease the thrombin formation due to binding of factor VII and IX to the nanoparticles, which resulted in depletion of the respective protein in solution. In contrast, carboxyl-modified nanoparticles were able to act as a surface for activation of the intrinsic pathway of blood coagulation in plasma. These results highlight the influence of nanoparticles on a biologically important pathway.
|
|
| 33. |
- Oslakovic, Cecilia, et al.
(författare)
-
Reevaluation of the role of HDL in the anticoagulant activated protein C system in humans.
- 2010
-
Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 120:5, s. 1396-1399
-
Tidskriftsartikel (refereegranskat)abstract
- HDL has anti-atherogenic properties, and plasma levels of HDL cholesterol correlate inversely with risk of coronary artery disease. HDL reportedly functions as a cofactor to the anticoagulant activated protein C (APC) in the degradation of factor Va (FVa). The aim of the present study was to elucidate the mechanism by which HDL functions as cofactor to APC. Consistent with a previous report, HDL isolated from human plasma by ultracentrifugation was found to stimulate APC-mediated degradation of FVa. However, further purification of HDL by gel filtration revealed that the stimulating activity was not a property of HDL. Instead, the stimulating activity eluted completely separately from HDL in the high-molecular-weight void volume fractions. The active portion of these fractions stimulated FVa degradation by APC and supported the assembly of factor Xa and FVa into a functional prothrombinase complex. Both the procoagulant and anticoagulant activities were blocked by addition of annexin V, suggesting that the active portion was negatively charged phospholipid membranes. These results demonstrate that HDL does not stimulate the APC/protein S effect and that the activity previously reported to be a property of HDL is instead caused by contaminating negatively charged phospholipid membranes.
|
|
| 34. |
- Oslakovic, Cecilia, et al.
(författare)
-
The role of phospholipid transfer protein in lipoprotein-mediated neutralization of the procoagulant effect of anionic liposomes.
- 2010
-
Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 8, s. 766-772
-
Tidskriftsartikel (refereegranskat)abstract
- Summary Background: Serum has the ability to neutralize the procoagulant properties of anionic liposomes, with transfer of phospholipids (PLs) to both high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles. Phospholipid transfer protein (PLTP) mediates transfer of PLs between HDL and other lipoproteins and conversion of HDL into larger and smaller particles. Objectives: To examine the role of PLTP in the neutralization of procoagulant liposomes. Methods: Procoagulant liposomes were incubated with different lipoproteins in the presence or absence of PLTP, and then tested for their ability to stimulate thrombin formation. Results and Conclusions: In the absence of added PLTP, the lipoprotein-enriched fraction, total HDL, HDL(3) and very high-density lipoprotein (VHDL) were all able to neutralize the procoagulant properties of the liposomes. In these samples, endogenous PLTP was present, as judged by western blotting. In contrast, no PLTP was present in LDL, HDL(2) and lipoprotein-deficient serum, all of which displayed no ability to neutralize the procoagulant liposomes. The phospholipid (PL) transfer activity was dependent on both enzyme (PLTP) and PL acceptor (lipoproteins). After treatment of the VHDL fraction with antiserum against PLTP, the neutralization of procoagulant activity was reduced, but could be regained by the addition of active PLTP. The neutralizing activity was dependent on a catalytically active form of PLTP, and addition of a low activity form of PLTP had no effect. In conclusion, PLTP was found to mediate transfer of anionic PLs to HDL and LDL, thereby neutralizing the effect of procoagulant liposomes resulting in a reduction of procoagulant activity.
|
|
| 35. |
|
|
| 36. |
- Ruiz Garcia, Mario, et al.
(författare)
-
High-Density Lipoprotein–Associated Apolipoprotein M Limits Endothelial Inflammation by Delivering Sphingosine-1-Phosphate to the Sphingosine-1-Phosphate Receptor 1
- 2017
-
Ingår i: Arteriosclerosis, Thrombosis, and Vascular Biology. - 1079-5642. ; 37:1, s. 118-129
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—: Plasma high-density lipoproteins (HDL) are potent antiatherogenic and anti-inflammatory particles. However, HDL particles are highly heterogenic in composition, and different HDL-mediated functions can be ascribed to different subclasses of HDL. Only a small HDL population contains apolipoprotein M (ApoM), which is the main plasma carrier of the bioactive lipid mediator sphingosine-1-phosphate (S1P). Vascular inflammation is modulated by S1P, but both pro- and anti-inflammatory roles have been ascribed to S1P. The goal of this study is to elucidate the role of ApoM and S1P in endothelial anti-inflammatory events related to HDL. APPROACH AND RESULTS—: Aortic or brain human primary endothelial cells were challenged with tumor necrosis factor-α (TNF-α) as inflammatory stimuli. The presence of recombinant ApoM-bound S1P or ApoM-containing HDL reduced the abundance of adhesion molecules in the cell surface, whereas ApoM and ApoM-lacking HDL did not. Specifically, ApoM-bound S1P decreased vascular adhesion molecule-1 (VCAM-1) and E-selectin surface abundance but not intercellular adhesion molecule-1. Albumin, which is an alternative S1P carrier, was less efficient in inhibiting VCAM-1 than ApoM-bound S1P. The activation of the S1P receptor 1 was sufficient and required to promote anti-inflammation. Moreover, ApoM-bound S1P induced the rearrangement of the expression of S1P-related genes to counteract TNF-α. Functionally, HDL/ApoM/S1P limited monocyte adhesion to the endothelium and maintained endothelial barrier integrity under inflammatory conditions. CONCLUSIONS—: ApoM-bound S1P is a key component of HDL and is responsible for several HDL-associated protective functions in the endothelium, including regulation of adhesion molecule abundance, leukocyte-endothelial adhesion, and endothelial barrier.
|
|
| 37. |
- Sahli, Hannah, et al.
(författare)
-
Impact of previous diverticulitis on 5-year survival and recurrence rates in patients with colorectal cancer
- 2023
-
Ingår i: Scandinavian Journal of Gastroenterology. - 0036-5521. ; 58:11, s. 1280-1285
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Diverticulitis and colorectal cancer (CRC) share epidemiological characteristics, but their relationship remains unknown. It is unclear if prognosis following CRC differ for patients with previous diverticulitis compared to those with sporadic cases and patients with inflammatory bowel disease or hereditary syndromes. Aim: The aim was to determine 5-year survival and recurrence after colorectal cancer in patients with previous diverticulitis, inflammatory bowel disease and hereditary colorectal cancer compared to sporadic cases. Methods: Patients <75 years of age diagnosed with colorectal cancer at Skåne University Hospital Malmö, Sweden, between January 1st 2012 and December 31st 2017 were identified through the Swedish colorectal cancer registry. Data was retrieved from the Swedish colorectal cancer registry and chart review. Five-year survival and recurrence in colorectal cancer patients with previous diverticulitis were compared to sporadic cases, inflammatory bowel disease associated and hereditary colorectal cancer. Results: The study cohort comprised 1052 patients, 28 (2.7%) with previous diverticulitis, 26 (2.5%) IBD, 4 (1.3%) hereditary syndromes and 984 (93.5%) sporadic cases. Patients with a history of acute complicated diverticulitis had a significantly lower 5-year survival rate (61.1%) and higher recurrence rate (38.9%) compared to sporadic cases (87.5% and 18.8% respectively). Conclusion: Patients with acute complicated diverticulitis had worse 5-year prognosis compared to sporadic cases. The results emphasize the importance of early detection of colorectal cancer in patients with acute complicated diverticulitis.
|
|
| 38. |
- Sanfins, Elodie, et al.
(författare)
-
Size-Dependent Effects of Nanoparticles on Enzymes in the Blood Coagulation Cascade.
- 2014
-
Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 14:8, s. 4736-4744
-
Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles (NPs) are increasingly used in diagnostic and drug delivery. After entering the bloodstream, a protein corona will form around NPs. The size and curvature of NPs is one of the major characteristics affecting the composition of bound protein in the corona. Key initiators of the intrinsic pathway of blood coagulation, the contact activation complex, (Kallikrein, Factor XII, and high molecular weight Kininogen) have previously been identified on NPs surfaces. We show that the functional impact of carboxyl-modified polystyrene NPs on these initiators of the intrinsic pathway is size dependent. NPs with high curvature affect the enzymatic activity differently from NPs with low curvature. The size dependency is evident in full blood plasma as well as in solutions of single coagulation factors. NPs induce significant alteration of the enzymatic activity in a size-dependent manner, and enzyme kinetics studies show a critical role for NPs surface area and curvature.
|
|
