| 1. |
- de Oliveira, Felipe Marques Souza, et al.
(författare)
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Detection of post-translational modifications using solid-phase proximity ligation assay.
- 2018
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Ingår i: New biotechnology. - : Elsevier BV. - 1876-4347 .- 1871-6784. ; 45:October, s. 51-59
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Tidskriftsartikel (refereegranskat)abstract
- Post-translational modifications (PTMs) regulate protein activities to help orchestrate and fine-tune cellular processes. Dysregulation of PTMs is often related with disorders and malignancies, and may serve as a precise biomarker of disease. Developing sensitive tools to measure and monitor low-abundant PTMs in tissue lysates or serum will be instrumental for opening up new PTM-based diagnostic avenues. Here, we investigate the use of solid-phase proximity ligation assay (SP-PLA) for detection of different PTMs. The assay depends on the recognition of the target protein molecule and its modification by three affinity binders. Using antibodies and lectins, we applied the method for detection of glycosylated CD44 and E-Cadherin, and phosphorylated p53 and EGFR. The assay was found to have superior dynamic range and limit of detection compared to standard ELISAs. In summary, we have established the use of SP-PLA as an appropriate method for sensitive detection of PTMs in lysates and sera, which may provide a basis for future PTM-based diagnostic and prognostic biomarkers.
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| 2. |
- Giesecke, Peter, et al.
(författare)
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All-cause and cardiovascular mortality risk after surgery versus radioiodine treatment for hyperthyroidism
- 2018
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Ingår i: British Journal of Surgery. - : John Wiley & Sons. - 0007-1323 .- 1365-2168. ; 105:3, s. 279-286
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Little is known about the long-term side-effects of different treatments for hyperthyroidism. The few studies previously published on the subject either included only women or focused mainly on cancer outcomes. This register study compared the impact of surgery versus radioiodine on all-cause and cause-specific mortality in a cohort of men and women.METHODS: Healthcare registers were used to find hyperthyroid patients over 35 years of age who were treated with radioiodine or surgery between 1976 and 2000. Comparisons between treatments were made to assess all-cause and cause-specific deaths to 2013. Three different statistical methods were applied: Cox regression, propensity score matching and inverse probability weighting.RESULTS: Of the 10 992 patients included, 10 250 had been treated with radioiodine (mean age 65·1 years; 8668 women, 84·6 per cent) and 742 had been treated surgically (mean age 44·1 years; 633 women, 85·3 per cent). Mean duration of follow-up varied between 16·3 and 22·3 years, depending on the statistical method used. All-cause mortality was significantly lower among surgically treated patients, with a hazard ratio of 0·82 in the regression analysis, 0·80 in propensity score matching and 0·85 in inverse probability weighting. This was due mainly to lower cardiovascular mortality in the surgical group. Men in particular seemed to benefit from surgery compared with radioiodine treatment.CONCLUSION: Compared with treatment with radioiodine, surgery for hyperthyroidism is associated with a lower risk of all-cause and cardiovascular mortality in the long term. This finding was more evident among men.
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| 3. |
- Giesecke, Peter, et al.
(författare)
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Increased Cardiovascular Mortality and Morbidity in Patients Treated for Toxic Nodular Goiter Compared to Graves' Disease and Nontoxic Goiter
- 2017
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Ingår i: Thyroid. - : Mary Ann Liebert. - 1050-7256 .- 1557-9077. ; 27:7, s. 878-885
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous research has suggested an increased risk of death and cardiovascular disease in patients treated for hyperthyroidism. However, studies on this subject are heterogeneous, often based on old data, or have not considered the impact that treatment for hyperthyroidism might have on cardiovascular risk. It is also unclear whether long-term prognosis differs between Graves' disease and toxic nodular goiter. The aim of this study was to use a very large cohort built on recent data to assess whether improvements in cardiovascular care might have changed the prognosis over time. The study also investigated the impact of different etiologies of hyperthyroidism.METHODS: This was an observational register study for the period 1976-2012, with subjects followed for a median period of 18.4 years. Study patients were Stockholm residents treated for Graves' disease or toxic nodular goiter with either radioactive iodine or surgery (N = 12,239). This group was compared to Stockholm residents treated for nontoxic goiter (N = 3685), with adjustments made for age, sex, comorbidities, and time of treatment. Comparisons were also made to the general population of Stockholm. Outcomes were assessed in terms of all-cause and cardiovascular mortality as well as cardiovascular morbidity.RESULTS: The hazard ratios (HR) for all-cause mortality and for cardiovascular mortality were 1.27 [confidence interval (CI) 1.20-1.35] and 1.29 [CI 1.17-1.42], respectively, for hyperthyroid patients compared to those with nontoxic goiter. For cardiovascular morbidity, the HR was 1.12 [CI 1.06-1.18]. Patients aged ≥45 years who were treated for toxic nodular goiter were generally at greater risk than others, and those included from the year 1990 and onwards were at greater risk than those included earlier. Increased all-cause mortality, as well as cardiovascular mortality and morbidity, were also seen in comparisons with the general population.CONCLUSIONS: This is the first large study to indicate that the long-term risk of death and cardiovascular disease in hyperthyroid subjects is due to the hyperthyroidism itself and not an effect of confounding introduced by its treatment. Much of the excess risk is confined to individuals treated for toxic nodular goiter. Despite advances in cardiovascular care during recent decades, hyperthyroidism is still a diagnosis associated with increased cardiovascular morbidity and mortality.
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| 4. |
- Ljunggren, Stefan, 1988-, et al.
(författare)
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Modified lipoproteins in periodontitis : a link to cardiovascular disease?
- 2019
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Ingår i: Bioscience Reports. - : Portland Press. - 0144-8463 .- 1573-4935. ; 39:3
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Tidskriftsartikel (refereegranskat)abstract
- There is a strong association between periodontal disease and atherosclerotic cardiovascular disorders. A key event in the development of atherosclerosis is accumulation of modified lipoproteins within the arterial wall. We hypothesize that patients with periodontitis have an altered lipoprotein profile towards an atherogenic form. Therefore, this study aims at identifying modifications of plasma lipoproteins in periodontitis. Lipoproteins from ten female patients with periodontitis and gender- and age-matched healthy controls were isolated by density-gradient-ultracentrifugation. Proteins were separated by two-dimensional gel-electrophoresis and identified by map-matching or by nano-liquid chromatography followed by mass spectrometry. ApoA-I methionine oxidation, Oxyblot, total antioxidant capacity and a multiplex of 71 inflammation-related plasma proteins were assessed.Reduced levels of apoJ, phospholipid transfer protein, apoF, complement C3, paraoxonase 3 and increased levels of alpha-1-antichymotrypsin, apoA-II, apoC-III were found in HDL from the patients. In LDL/VLDL, the levels of apoL-1 and platelet-activating factor acetylhydrolase as well as apo-B fragments were increased. Methionine oxidation of apoA-I was increased in HDL and showed a relationship with periodontal parameters. Alpha-1 antitrypsin and alpha-2-HS glycoprotein were oxidised in LDL/VLDL and antioxidant capacity was increased in the patient group. 17 inflammation-related proteins were important for group separation with the highest discriminating proteins identified as IL-21, Fractalkine, IL-17F, IL-7, IL-1RA and IL-2.Patients with periodontitis have an altered plasma lipoprotein profile, defined by altered protein levels as well as posttranslational and other structural modifications towards an atherogenic form, which supports a role of modified plasma lipoproteins as central in the link between periodontal and cardiovascular disease (CVD).
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| 5. |
- Lönn, Johanna, et al.
(författare)
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Lipoprotein modifications by gingipains of Porphyromonas gingivalis
- 2018
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Ingår i: Journal of Periodontal Research. - : Wiley-Blackwell Publishing Inc.. - 0022-3484 .- 1600-0765. ; 53:3, s. 403-413
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Several studies have shown an association between periodontitis and cardiovascular disease (CVD). Atherosclerosis is the major cause of CVD, and a key event in the development of atherosclerosis is accumulation of lipoproteins within the arterial wall. Bacteria are the primary etiologic agents in periodontitis and Porphyromonas gingivalis is the major pathogen in the disease. Several studies support a role of modified low-density lipoprotein (LDL) in atherogenesis; however, the pathogenic stimuli that induce the changes and the mechanisms by which this occur are unknown. This study aims to identify alterations in plasma lipoproteins induced by the periodontopathic species of bacterium, P. gingivalis, in vitro.MATERIAL AND METHODS: Plasma lipoproteins were isolated from whole blood treated with wild-type and gingipain-mutant (lacking either the Rgp- or Kgp gingipains) P. gingivalis by density/gradient-ultracentrifugation and were studied using 2-dimensional gel electrophoresis followed by matrix-assisted laser desorption/ionization mass spectrometry. Porphyromonas gingivalis-induced lipid peroxidation and antioxidant levels were measured by thiobarbituric acid-reactive substances and antioxidant assay kits, respectively, and lumiaggregometry was used for measurement of reactive oxygen species (ROS) and aggregation.RESULTS: Porphyromonas gingivalis exerted substantial proteolytic effects on the lipoproteins. The Rgp gingipains were responsible for producing 2 apoE fragments, as well as 2 apoB-100 fragments, in LDL, and the Kgp gingipain produced an unidentified fragment in high-density lipoproteins. Porphyromonas gingivalis and its different gingipain variants induced ROS and consumed antioxidants. Both the Rgp and Kgp gingipains were involved in inducing lipid peroxidation.CONCLUSIONS: Porphyromonas gingivalis has the potential to change the expression of lipoproteins in blood, which may represent a crucial link between periodontitis and CVD.
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