| 1. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 2. |
- Kapferer-Seebacher, Ines, et al.
(författare)
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Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement
- 2016
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Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 99:5, s. 1005-1014
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Tidskriftsartikel (refereegranskat)abstract
- Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped to an approximately 5.8 Mb region at 12p13.1 but no candidate gene was identified. In an international consortium we recruited 19 independent families comprising 107 individuals with pEDS to identify the locus, characterize the clinical details in those with defined genetic causes, and try to understand the physiological basis of the condition. In 17 of these families, we identified heterozygous missense or in-frame insertion/deletion mutations in C1R (15 families) or C1S (2 families), contiguous genes in the mapped locus that encode subunits C1r and C1s of the first component of the classical complement pathway. These two proteins form a heterotetramer that then combines with six C1q subunits. Pathogenic variants involve the subunit interfaces or inter-domain hinges of C1r and C1s and are associated with intracellular retention and mild endoplasmic reticulum enlargement. Clinical features of affected individuals in these families include rapidly progressing periodontitis with onset in the teens or childhood, a previously unrecognized lack of attached gingiva, pretibial hyperpigmentation, skin and vascular fragility, easy bruising, and variable musculoskeletal symptoms. Our findings open a connection between the inflammatory classical complement pathway and connective tissue homeostasis.
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| 3. |
- Forsberg, Anna, et al.
(författare)
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Colonoscopy findings in high-risk individuals compared to an average-risk control population
- 2015
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 50:7, s. 866-874
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: There is clear evidence of reduced morbidity and mortality from regular colonoscopy programs in patients with Lynch syndrome (LS). Today, also individuals with empirically increased risks of colorectal cancer (CRC) are offered colonoscopic surveillance. The aim was to compare the findings at the first screening colonoscopy in LS carriers, and individuals with an increased risk of bowel cancer due to family history of CRC with a control population. Methods: Altogether 1397 individuals with an increased risk for CRC were divided in four risk groups: one with LS carriers and three groups with individuals with different family history of CRC. The findings were compared between the different risk groups and a control group consisting of 745 individuals from a control population who took part in a population-based colonoscopy study. Results: In LS, 30% of the individuals had adenomas and 10% advanced adenomas. The corresponding figures in the other risk groups were 14-24% and 4-7%, compared with 10% and 3% in the control group. The relative risk of having adenomas and advanced adenomas was, compared to controls, significantly higher for all risk groups except the group with the lowest risk. Age was a strong predictor for adenomas and advanced adenomas in both risk individuals and controls. Conclusions: Individuals with a family history of CRC have a high prevalence and cumulative risk of adenomas and advanced adenomas, and screening is motivated also in this risk group.
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| 4. |
- Forsberg, Anna M., et al.
(författare)
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Prevalence of colonic neoplasia and advanced lesions in the normal population : a prospective population-based colonoscopy study
- 2012
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 47:2, s. 184-90
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Tidskriftsartikel (refereegranskat)abstract
- Objective. There are few prospective studies of the prevalence of colonic neoplasia in the normal population. In order to properly evaluate screening-protocols for colorectal cancer in risk groups (e.g., older subjects or those with a family history), it is essential to know the prevalence of adenomas and cancer in the normal population. Methods. A prospective population-based colonoscopy study on 745 individuals born in Sweden aged 19-70 years was conducted (mean age 51.1 years). All polyps seen were retrieved and examined. Results. Out of the 745 individuals 27% had polyps, regardless of kind. Adenomas were found in 10% of the individuals and finding of adenomas was positively correlated to higher age. Men had adenomas in 15% and women in 6% of the cases. Women had a right-sided dominance of adenomas. Hyperplastic polyps were seen in 21% of the individuals. The presence of hyperplastic polyps was significantly positively correlated to the presence of adenomas. Advanced adenomas were seen in 2.8% of the study participants, but no cancers were detected. Conclusion. One in 10 healthy subjects had an adenoma but advanced adenomas were uncommon. Men and women have a different adenoma prevalence and localization. The results provide baseline European data for evaluating colonoscopy screening-protocols for colorectal cancer risk groups, and the findings may have implications for colon cancer screening in the normal, otherwise-healthy population.
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| 5. |
- Levinsson, Anna, et al.
(författare)
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Interaction effects of long-term air pollution exposure and variants in the GSTP1, GSTT1 and GSTCD genes on risk of acute myocardial infarction and hypertension : a case-control study
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e99043-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Experimental and epidemiological studies have reported associations between air pollution exposure, in particular related to vehicle exhaust, and cardiovascular disease. A potential pathophysiological pathway is pollution-induced pulmonary oxidative stress, with secondary systemic inflammation. Genetic polymorphisms in genes implicated in oxidative stress, such as GSTP1, GSTT1 and GSTCD, may contribute to determining individual susceptibility to air pollution as a promoter of coronary vulnerability.AIMS: We aimed to investigate effects of long-term traffic-related air pollution exposure, as well as variants in GSTP1, GSTT1 and GSTCD, on risk of acute myocardial infarction (AMI) and hypertension. In addition, we studied whether air pollution effects were modified by the investigated genetic variants.METHODS: Genotype data at 7 single nucleotide polymorphisms (SNPs) in the GSTP1 gene, and one in each of the GSTT1 and GSTCD genes, as well as air pollution exposure estimates, were available for 119 AMI cases and 1310 randomly selected population controls. Population control individuals with systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg or on daily antihypertensive medication were defined as hypertensive (n = 468). Individual air pollution exposure levels were modeled as annual means of NO₂ (marker of vehicle exhaust pollutants) using central monitoring data and dispersion models, linking to participants' home addresses.RESULTS: Air pollution was significantly associated with risk of AMI: OR 1.78 (95%CI 1.04-3.03) per 10 µg/m³ of long-term NO₂ exposure. Three GSTP1 SNPs were significantly associated with hypertension. The effect of air pollution on risk of AMI varied by genotype strata, although the suggested interaction was not significant. We saw no obvious interaction between genetic variants in the GST genes and air pollution exposure for hypertension.CONCLUSION: Air pollution exposure entails an increased risk of AMI, and this risk differed over genotype strata for variants in the GSTP1, GSTT1 and GSTCD genes, albeit not statistically-significantly.
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| 6. |
- Levinsson, Anna, et al.
(författare)
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Nitric oxide synthase (NOS) single nucleotide polymorphisms are associated with coronary heart disease and hypertension in the INTERGENE study
- 2014
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Ingår i: Nitric oxide. - : Elsevier BV. - 1089-8603 .- 1089-8611. ; 39, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Nitric oxide synthase (NOS) exists in three distinct isoforms, each encoded by a specific gene: neuronal NOS (NOS1 gene), inducible NOS (NOS2 gene) and endothelial NOS (NOS3 gene). Single nucleotide polymorphisms (SNPs) in NOS genes have been associated with cardiovascular pathology. We aimed to comprehensively investigate which NOS gene variants are most strongly associated with coronary heart disease (CHD) and hypertension, using a set of tagging SNPs with good coverage across the 3 genes. Method and results: CHD cases (n = 560) and randomly selected population controls (n = 2791) were genotyped at 58 SNPs in the NOS genes. Control individuals with systolic blood pressure >= 140, diastolic blood pressure >= 90 or on antihypertensive medication were defined as hypertensive. A structured stepwise logistic regression approach was used to select the SNPs most strongly associated with CHD and hypertension. Method and results: NOS1 SNP rs3782218 showed the most consistent association with both phenotypes, odds ratio 0.59 (95% confidence interval 0.44-0.80) and 0.81 (0.67-0.97) per T-allele for CHD and hypertension respectively. For CHD, another NOS1 SNP (rs2682826) and a NOS3 SNP (rs1549758) also showed effect. For hypertension associations were seen for additional SNPs including NOS3 SNP rs3918226, previously associated with hypertension in genome-wide association study (GWAS) data. Conclusion: We found a previously unreported association between NOS1 SNP rs3782218 and both CHD and hypertension, and confirmed NOS1 as the most important NOS risk gene for CHD. In contrast, variants in all three NOS genes were seen to be associated with hypertension in the same source population. (C) 2014 Elsevier Inc. All rights reserved.
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| 7. |
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| 8. |
- Baderkhan, Hassan, et al.
(författare)
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Celiprolol Treatment in Patients with Vascular Ehlers-Danlos Synurome
- 2021
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier. - 1078-5884 .- 1532-2165. ; 61:2, s. 326-331
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Tidskriftsartikel (refereegranskat)abstract
- Objecti_ Vascular Ehlers-Danlos syndrome (vEDS) is a rare monogenetic disease caused by pathogenic variants in procollagen 3A1. Arterial rupture is the most serious clinical manifestation. A randomised controlled trial, the Beta-Blockers in Ehlers-Danlos Syndrome Treatment (BBEST) trial, reported a significant protective effect of the beta blocker celiprolol. The aim was to study the outcome of celiprolol treatment in a cohort of Swedish patients with vEDS. Methods: Uppsala is a national referral centre for patients with vEDS. They are assessed by vascular surgeons, angiologists, and clinical geneticists. Family history, previous and future clinical events, medication, and side effects are registered. Celiprolol was administered twice daily and titrated up to a maximum dose of 400 mg daily. Logistic regression was used to analyse predictors of vascular events. Results: Forty patients with pathogenic sequence variants in COL3A1 were offered treatment with celiprolol in the period 2011-2019. The median follow up was 22 months (range 1-98 months); total follow up was 106 patient years. In two patients, uptitration of the dose is ongoing. Of the remaining 38, 26 (65%) patients reached the target dose of 400 mg daily. Dose uptitration was unsuccessful in six patients because of side effects; one died before reaching the maximum dose, and five terminated the treatment. Five major vascular events occurred; four were fatal (ruptured ascending aorta; aortic rupture after type B dissection; ruptured cerebral aneurysm; and ruptured pulmonary artery). One bled from a branch of the internal iliac artery, which was successfully coiled endovascularly. The annual risk of a major vascular event was 4.7% (n = 5/106), similar to the treatment arm of the BBEST trial (5%) and lower than in the control arm of the same trial (12%). No significant predictor of vascular events was identified. Conclusion: Treatment with celiprolol is tolerated in most patients with vEDS. Despite fatal vascular events, these observations suggest that celiprolol may have a protective effect in vEDS.
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| 9. |
- Berggren, Anna M., et al.
(författare)
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Short‐chain fatty acid content and pH in caecum of rats fed various sources of starch
- 1995
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Ingår i: Journal of the Science of Food and Agriculture. - : Wiley. - 0022-5142 .- 1097-0010. ; 68:2, s. 241-248
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Tidskriftsartikel (refereegranskat)abstract
- Caecal pH and contents of short‐chain fatty acids (SCFA) were registered in rats fed three potential sources of resistant starch (RS); raw pea starch, raw potato starch, and an RS‐enriched preparation obtained from wheat starch by autoclaving and enzymatic incubation. Small intestinal digestibility and delivery of RS to the hind‐gut in the case of raw starches were determined by analysis of faecal starch in animals treated with antibiotics to prevent hind‐gut fermentation. RS content in the RS‐enriched preparation was determined as total starch remaining in an enzymatic gravimetric dietary fibre residue. The fermentability of RS was estimated from the faecal recovery of starch in normal animals with intact hind‐gut microflora. Approximately 35 g per 100 g and 32 g per 100 g were RS in the case of raw potato starch and the RS‐enriched preparation, respectively, versus only 1 g per 100 g in the case of raw pea starch. The caecal pH decreased with all test diets, being most significant with raw potato starch. SCFA production and faecal bulking were negligible with raw pea starch, whereas both raw potato starch and the RS‐enriched preparation significantly increased these parameters. The fermentability of RS in raw potato starch and the RS‐enriched preparation was similar, or about 60–70%. If calculated on basis of fermented amount, RS in raw potato starch was more potent in generating SCFA (49 μmol g−1) than in the RS‐enriched preparation (19 μmol g−1). RS in raw potato starch also displayed the highest faecal bulking capacity. In fact, the faecal dry weight increased more than expected merely from delivery of RS. The relative proportion in caecal contents of acetic‐, propionic‐ and butyric acid was 70, 17 and 8%, respectively, with no significant differences between the three sources of RS.
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| 10. |
- Berggren, Anna, et al.
(författare)
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Short-chain fatty acid content and pH in caecum of rats given various sources of carbohydrates
- 1993
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Ingår i: Journal of the Science of Food and Agriculture. - : Wiley. - 0022-5142 .- 1097-0010. ; 63:4, s. 397-406
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Tidskriftsartikel (refereegranskat)abstract
- The caecal content of short‐chain fatty acids (SCFA; acetic, propionic and butyric acid), caecal pH, fermentability and dry matter digestibility (DMD) were examined through balance experiments in rats fed 11 various indigestible carbohydrates. The following carbohydrate sources were incorporated into test diets: cellulose, oat husk, wheat bran, oat bran, pea fibre, linseed fibre, low methoxylated (LM)‐pectin, guargum, β‐glucans, neosugar and raffinose. The indigestible carbohydrates, except for those in wheat bran, oat husk and cellulose, were highly fermented, ie > 90%. Caecal pH varied between 5·6 and 7·8, with neosugar and raffinose causing the lowest pH and the fibre‐free diet and the diet with oat husk the highest. The caecal pool sizes of SCFA were highest with raffinose, β‐glucans, LM‐pectin, guargum and linseed fibre (335‐400 μmol) while pea fibre, wheat bran, oat bran and neosugar gave intermediate levels (137–227 μmol). The pool size with oat husk and cellulose was similar as with the basal diet (45–64 μmol). A high proportion of propionic acid was obtained with guargum and linseed fibre, whereas acetic acid was the predominant product in case of LM‐pectin. On the other hand, linseed fibre gave a remarkably low proportion of butyric acid. The quantity fermented and caecal pH correlated well to the amount of SCFA with most materials (r = 0·96 and r = −0·87, respectively), an exception was neosugar and in case of fermentability also oat bran. DMD values with most of the easily fermented carbohydrates were high (>96%). Exceptions were diets with β‐glucans and oat bran which caused low DMD values, about 93%. It is concluded that indigestible carbohydrates may differ in ability to lower caecal pH and to form SCFA during fermentation.
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