| 1. |
- Carlsson, Björn, 1958, et al.
(författare)
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Obese (ob) gene defects are rare in human obesity
- 1997
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Ingår i: Obesity Research. - 1071-7323 .- 1550-8528. ; 5:1, s. 30-5
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Tidskriftsartikel (refereegranskat)abstract
- Our knowledge of the role of the recently cloned ob-protein (leptin) in the regulation of body fat stores is largely derived from experiments performed in mice. Different mouse models exhibit abnormalities in ob-gene expression, with extreme overexpression in mice which lack bioactive ob-protein, have nonfunctional ob-receptors or hypothalamic lesions, and undetectable expression in mice with suggested defects in regulatory elements. The aim of this study is to examine if defects, corresponding to those in mice, exist in human obesity. Adipose tissue was obtained from 94 adult obese subjects and from six children who had developed obesity after surgery in the hypothalamic region. Total RNA was isolated and ob-gene expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot. The coding region of the ob-gene was sequenced in both directions in the 94 obese adults. No mutations were detected in the coding region of the ob-gene and ob-gene expression was detectable in all subjects and none of the subjects had an extreme overexpression. There was no systematic increase in ob-expression in obese children with hypothalamic disease compared to their healthy brothers and sisters. These results show that severe abnormalities involving the ob-gene, analogous to those described in mouse models, are rare in human obesity. We therefore conclude that the cloning and subsequent analysis of the ob-gene has not provided information that can, by itself, explain the genetic component in the development of human obesity.
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| 2. |
- Carlsson, Lena M S, 1957, et al.
(författare)
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Life expectancy after bariatric surgery or usual care in patients with or without baseline type 2 diabetes in Swedish Obese Subjects.
- 2023
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Ingår i: International journal of obesity (2005). - 1476-5497. ; 47, s. 931-8
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Tidskriftsartikel (refereegranskat)abstract
- To determine life expectancy and causes of death after bariatric surgery in relation to baseline type 2 diabetes (T2D) in the prospective, Swedish Obese Subjects study.The study included 2010 patients with obesity who underwent bariatric surgery and 2037 matched controls, eligible for surgery. The surgery group underwent gastric bypass (n=265), banding (n=376), or vertical banded gastroplasty (n=1369). The control group (n=2037) received usual obesity care. Causes of death were obtained from the Swedish Cause of Death Register, case sheets and autopsy reports, in patients with baseline T2D (n=392 surgery patients/n=305 controls) or non-T2D (n=1609 surgery patients/n=1726 controls) during a median follow-up 26 years.In T2D and non-T2D subgroups, bariatric surgery was associated with increased life expectancy (2.1, 95% confidence interval (95% CI) 0.2-4.0; and 1.6, 0.5-2.7 years, respectively) and reduced overall mortality (adjusted hazard ratio (adjHR)=0.77, 95% CI: 0.61-0.97; and 0.82, 0.72-0.94, respectively), and the treatment benefit was similar (interaction p=0.615). Bariatric surgery was associated with reduced cardiovascular mortality in both subgroups (adjHR=0.65, 95% CI: 0.46-0.91; and 0.70, 0.55-0.88, respectively (interaction p=0.516)).Bariatric surgery is associated with similar reduction of overall and cardiovascular mortality and increased life expectancy regardless of baseline diabetes status.
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| 3. |
- Handin, Niklas, et al.
(författare)
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Proteome deconvolution of liver biopsies reveals hepatic cell composition as an important marker of fibrosis
- 2023
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Ingår i: Computational and Structural Biotechnology Journal. - : Elsevier. - 2001-0370. ; 21, s. 4361-4369
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Tidskriftsartikel (refereegranskat)abstract
- Human liver tissue is composed of heterogeneous mixtures of different cell types and their cellular stoichiometry can provide information on hepatic physiology and disease progression. Deconvolution algorithms for the identification of cell types and their proportions have recently been developed for transcriptomic data. However, no method for the deconvolution of bulk proteomics data has been presented to date. Here, we show that proteomes, which usually contain less data than transcriptomes, can provide useful information for cell type deconvolution using different algorithms. We demonstrate that proteomes from defined mixtures of cell lines, isolated primary liver cells, and human liver biopsies can be deconvoluted with high accuracy. In contrast to transcriptome-based deconvolution, liver tissue proteomes also provided information about extracellular compartments. Using deconvolution of proteomics data from liver biopsies of 56 patients undergoing Roux-en-Y gastric bypass surgery we show that proportions of immune and stellate cells correlate with inflammatory markers and altered composition of extracellular matrix proteins characteristic of early-stage fibrosis. Our results thus demonstrate that proteome deconvolution can be used as a molecular microscope for investigations of the composition of cell types, extracellular compartments, and for exploring cell-type specific pathological events. We anticipate that these findings will allow the refinement of retrospective analyses of the growing number of proteome datasets from various liver disease states and pave the way for AI-supported clinical and preclinical diagnostics.
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| 4. |
- Hjelmesaeth, J., et al.
(författare)
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Impact of body weight, low energy diet and gastric bypass on drug bioavailability, cardiovascular risk factors and metabolic biomarkers: protocol for an open, non-randomised, three-armed single centre study (COCKTAIL)
- 2018
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Ingår i: Bmj Open. - 2044-6055. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Roux-en-Y gastric bypass (GBP) is associated with changes in cardiometabolic risk factors and bioavailability of drugs, but whether these changes are induced by calorie restriction, the weight loss or surgery per se, remains uncertain. The COCKTAIL study was designed to disentangle the short-term (6 weeks) metabolic and pharmacokinetic effects of GBP and a very low energy diet (VLED) by inducing a similar weight loss in the two groups. Methods and analysis This open, non-randomised, three-armed, single-centre study is performed at a tertiary care centre in Norway. It aims to compare the short-term (6 weeks) and long-term (2 years) effects of GBP and VLED on, first, bioavailability and pharmacokinetics (24 hours) of probe drugs and biomarkers and, second, their effects on metabolism, cardiometabolic risk factors and biomarkers. The primary outcomes will be measured as changes in: (1) all six probe drugs by absolute bioavailability area under the curve (AUC(oral)/AUC(iv)) of midazolam (CYP3A4 probe), systemic exposure (AUC(oral)) of digoxin and rosuvastatin and drug:metabolite ratios for omeprazole, losartan and caffeine, levels of endogenous CYP3A biomarkers and genotypic variation, changes in the expression and activity data of the drug-metabolising, drug transport and drug regulatory proteins in biopsies from various organs and (2) body composition, cardiometabolic risk factors and metabolic biomarkers. Ethics and dissemination The COCKTAIL protocol was reviewed and approved by the Regional Committee for Medical and Health Research Ethics (Ref: 2013/2379/REK serest A). The results will be disseminated to academic and health professional audiences and the public via presentations at conferences, publications in peer-reviewed journals and press releases and provided to all participants.
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| 5. |
- Hortlund, Cecilia, 1989-
(författare)
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Svenskar, krigare, söner av Finland : maskulinitet, minoritetsnationalism, nationell identitet och sociala skillnader inom svenskspråkiga skyddskårer i Österbotten och Åboland 1918-1939
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation is a study on the Swedish-speaking Civil Guards in Ostrobothnia and Turunmaa in Finland during the Finnish interwar period (1918-1939). The study focuses on how they created their own Swedish minority nationalist identity in regards to the national project of White (bourgeois) Finland. They did so with the aid of conceptions and ideals of masculinities, nationalism, national identity and social differences. The Swedish-speaking Civil Guards were part of a turbulent time in Finnish history with Finland declaring independence and separating from Russia in 1917. The Finnish Civil Guard was an organisation forged by the Finnish Civil War of 1918 where it acted as the primary armed force on the White (bourgeois) side of the conflict. In 1919 the Civil Guard had about 107 000 members, which was the highest number during their active years, and membership was voluntary. During the 1920’s the total number of members remained relatively steady at about 80 000 members.This study implements an intersectional perspective consisting of four different main categories: masculinities, minority nationalism, national identity and social differences. These categories are then analysed together with theory on nationalist projects as presented by Nira Yuval-Davis. The empirical basis of this study is composed of material such as yearly summaries, minutes, and similar documents from different local civil guards in the two Swedish-speaking civil guard districts of Vaasa and Turunmaa. The study also bases itself on an analysis of two civil guard periodicals: Svenska Skyddskåristen (1919-1927) and Skyddskåristen (1928-1939).This study shows that the Swedish-speaking Civil Guards reproduced their own version of a bourgeois minority nationalist identity where militarised masculine ideals blended together with a focus on their Swedish heritage and blood, the responsibilities to the Finnish nation, and conceptions on social differences where different members of society received different status in their narrative. They romanticised the idea of the Ostrobothnian peasant as the cradle of Swedish heritage in Finland and a symbol of strength, honour and power. In addition, they reproduced a myth of heroic, manly sacrifice for the nation that was meant to urge its members and the Finnish people to act and defend the country.
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| 6. |
- Karlsson, Cecilia, 1968, et al.
(författare)
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Development of Human Target Validation Classification that Predicts Future Clinical Efficacy
- 2019
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Ingår i: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0022-3565 .- 1521-0103. ; 368:2, s. 255-261
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Tidskriftsartikel (refereegranskat)abstract
- Fewer new medicines have become available to patients during the last decades. Clinical efficacy failures in late-phase development have been identified as a common cause of this decline. Improved ways to ensure early selection of the right drug targets when it comes to efficacy is therefore a highly desirable goal. The aim of this work was to develop a strategy to facilitate selection of novel targets already in the discovery phase that later on in clinical development would demonstrate efficacy. A cross-functional team at AstraZeneca with extensive experience in drug discovery and development participated in several workshops to identify the critical elements that contribute to building human target validation [(HTV); the relevance of the target from a human perspective]. The elements were consolidated into a 10-point HTV classification system that was ranked from lowest to highest in terms of perceived impact on future clinical efficacy. Using 50 years of legacy research and development data, the ability of the 10-point HTV classification to predict future clinical efficacy was evaluated. Drug targets were classified as having low, medium, or high HTV at the time of candidate drug selection. Comparing this HTV classification with later clinical development efficacy data showed that HTV classification was highly predictive of future clinical efficacy success. This new strategy for HTV assessment provides a novel approach to early prediction of clinical efficacy and a better understanding of portfolio risk.
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| 7. |
- Karlsson, Cecilia, 1968, et al.
(författare)
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Identification of Proteins Associated with the Early Restoration of Insulin Sensitivity After Biliopancreatic Diversion
- 2020
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 105:11
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Tidskriftsartikel (refereegranskat)abstract
- Context: Insulin resistance (IR) is a risk factor for type 2 diabetes, diabetic kidney disease, cardiovascular disease and nonalcoholic steatohepatitis. Biliopancreatic diversion (BPD) is the most effective form of bariatric surgery for improving insulin sensitivity. Objective: To identify plasma proteins correlating with the early restoration of insulin sensitivity after BPD. Design: Prospective single-center study including 20 insulin-resistant men with morbid obesity scheduled for BPD. Patient characteristics and blood samples were repeatedly collected from baseline up to 4 weeks postsurgery. IR was assessed by homeostatic model assessment for insulin resistance (HOMA-IR), Matsuda Index, and by studying metabolic profiles during meal tolerance tests. Unbiased proteomic analysis was performed to identify plasma proteins altered by BPD. Detailed plasma profiles were made on a selected set of proteins by targeted multiple reaction monitoring mass spectrometry (MRM/MS). Changes in plasma proteome were evaluated in relation to metabolic and inflammatory changes. Results: BPD resulted in improved insulin sensitivity and reduced body weight. Proteomic analysis identified 29 proteins that changed following BPD. Changes in plasma levels of afamin, apolipoprotein A-IV (ApoA4), and apolipoprotein A-II (ApoA2) correlated significantly with changes in IR. Conclusion: Circulating levels of afamin, ApoA4, and ApoA2 were associated with and may contribute to the rapid improvement in insulin sensitivity after BPD.
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| 8. |
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| 9. |
- Karlsson, Katarina
(författare)
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Exploring symptom clusters in patients with lung cancer
- 2024
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis explored symptom clusters in patients with lung cancer before, during and after oncological treatment. A literature review and an interview study was used to explore the symptom cluster experience from the patients’ perspective. A large diversity of symptom cluster constellations were identified, in which fatigue was the most commonly occurring symptom, followed by dyspnea, pain, depression, cough and nutritional impact symptoms. Many symptom assessment instruments were identified, measuring mostly the intensity-dimension alone or in combination with timing. The results also stress that living with symptom clusters during treatment is more about survival than actually living. Patients’ symptom management strategies were shaped by impacting conditions such as knowledge and earlier experience of symptoms. Symptoms were often regarded as unavoidable by the patients and something to accept. How symptoms were recognized by health care professionals further added to the normalization of symptom clusters. Subsequently, patients would not always ask for support, and their quality of life was negatively affected. Holistic person-centered care including multi-dimensional symptom assessment is considered essential to ensure adequate symptom cluster management for patients with lung cancer.
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| 10. |
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