| 1. |
- Mathioudaki, Argyri, Ph.D student, 1986-, et al.
(författare)
-
Replication and fine mapping of ankylosing spondylitis replicated loci in the Swedish population reveal different CCHCR1 protective haplotypes
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: The genetics of ankylosing spondylitis (AS) derives mainly from studies performed in large cohorts of British origin. However, within Europe, disease prevalence is higher in Sweden, and so we investigated the reproducibility of known AS susceptibility patterns in a homogeneous Swedish cohort.Methods: The replication power of the Swedish cohort was examined and a set of published SNP associations intersected with genotypes from an existing targeted sequencing study using these individuals (381 controls; 310 AS cases). To elucidate whether replication patterns derived from population subsampling or genetic similarity, allele frequency data from additional British and Swedish control populations were examined for genetic differentiation (FST). Replicated loci were fine mapped to investigate associations in more detail, and signals were dissected with haplotype analysis and functional annotation.Results: The study had 80% power to find variants of strong effect (Odds ratio, OR>2) given a wide range of risk allele frequencies (0.2-3), tagging HLA-B,CCHCR1and IL23R. The replication pattern was not due to European population genetic distance and fine mapping revealed genome-wide repositioned associations in HLA-Band CCHCR1, independent from the published associations (p-value < 2 x10-8, r2 < 0.3). The CCHCR1 locus showed two protective haplotype blocks (B1-1 and B2-1), independent from HLA-B signals (B1-1: r2 = 0.39, B2-2:r2=0.07), where 74% of controls were carrying 2 copies of the protective haplotypes (B1-1 and B2-1: OR=0.3, p-value = 1.2 x 10-45). Interestingly, while both haplotypes span CCHCR1, the effect of each haplotype is likely in cis, with eQTL evidence pointing to the regulation of TCF19(B1-1) and POU5F1(B1-2).Conclusions: Both European populations share key disease loci, but the Swedish cohort revealed fine-scale genetic differences, that may point to gene regulation. This study utilized a different variant resolution, and by doing so demonstrated that smaller populations have the potential to reveal new AS pathogenesis mechanisms and that further study of the Swedish population is warranted.
|
|
| 2. |
- Axelsson, Daniel, 1974-
(författare)
-
Postpartum infections; prevalence, associated obstetric factors and the role of vitamin D
- 2019
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Postpartum infections are a major cause of maternal mortality and morbidity worldwide. Breast infection, endometritis, urinary tract infection and wound infections are the most common postpartum infections and together they affect almost 20% of women after childbirth. Some risk factors for postpartum infections, for example cesarean section, have been relatively well studied, but other presumable risk factors are yet to be confirmed.The proportion of pregnant women who are overweight or obese is increasing in most parts of the world. Increased maternal body mass index (BMI) is associated with maternal and infant morbidity. The association between overweight / obesity and postpartum infections is incompletely understood. Vitamin D deficiency has in epidemiological studies been shown to increase the risk of various infections. Furthermore, vitamin D is an important factor in the human immune system. Concomitantly, vitamin D supplementation seems protective against some types of infections. Whether vitamin D deficiency is a risk factor for postpartum infections has not been studied.Material and Methods: In a population-based observational study using questionnaires, the prevalences of postpartum wound infections, endometritis, urinary tract infections and mastitis in the southeast region of Sweden were estimated (Paper I). All women giving birth in the region during one year (n=11 124) were asked to participate. Papers II and III were cohort studies based on all deliveries in Sweden during eight years (2005-2012). Data sources were the Swedish Medical Birth Register, the Swedish National Patient Register and the Swedish Prescribed Drugs Register. In paper II all term deliveries were included (n=795 072). Risk factors for postpartum wound infections, endometritis and urinary tract infection were evaluated. Paper III included all deliveries (n=841 780) and examined the impact of BMI on the risk of postpartum wound infections, endometritis and breast abscess after different modes of delivery. Infections were defined as the presence of applicable ICD-10 codes. The Mantel-Haenszel technique was used to calculate adjusted odds ratios. In paper IV the association between vitamin D deficiency and overall postpartum infectious morbidity was analyzed. Serum samples from the Pregnancy Biobank in Linköping, drawn at the time of delivery, were used to determine concentrations of 25-hydroxyvitamin D in 1397 women. ICD-10 codes were extracted from the women’s medical records. The prevalence of vitamin D deficiency was calculated and adjusted odds ratios for postpartum infections were estimated with multivariable logistic regression analysis.Results: More than one out of ten women in southeast Sweden reported wound infections; endometritis, urinary tract infection or mastitis postpartum and 7.5% reported antibiotic treatment for infection. Cesarean section was the strongest risk factor for wound infection, followed by obstetric anal sphincter injuries and episiotomy. For endometritis, the strongest risk factors were anemia, manual placental removal and emergency cesarean section. Urinary tract infection was associated with anemia, instrumental vaginal delivery and emergency cesarean section. There was a dose-dependent increased risk of postpartum infection with higher BMI. For morbidly obese women the risk of infection was over 50% higher than for normal weight women. The risk of endometritis after normal vaginal delivery increased the higher the BMI, as did the risk of wound infection after cesarean section, regardless of the type of cesarean section. For breast abscess, there was an inverse association with BMI.Vitamin D deficiency was present among almost 60% of pregnant women at the time of delivery. No association between vitamin D deficiency and postpartum infections was found.Conclusions: Every tenth Swedish woman acquired an infection postpartum and three quarters of them received antibiotics for infection. Anemia was an important risk factor for postpartum infection, and the strongest risk factor for endometritis and urinary tract infection. Strong efforts should be made to reduce blood loss during and after childbirth. This thesis confirmed cesarean section as a major risk factor for postpartum infection, especially wound infection. The risk increased if the woman was overweight or obese, regardless of whether it was a planned or an emergency cesarean section.Vitamin D deficiency was common among Swedish pregnant women, but it was not found to be associated with postpartum infections.
|
|
| 3. |
- Callegaro, Luca, et al.
(författare)
-
The EMPIR Project GIQS : Graphene Impedance Quantum Standard
- 2020
-
Ingår i: 2020 Conference on Precision Electromagnetic Measurements (CPEM). ; , s. 1-2
-
Konferensbidrag (refereegranskat)abstract
- GIQS: Graphene Impedance Quantum Standard is a Joint Research Project of the European Metrology Programme for Innovation and Research (EMPIR). The project objective is to combine novel digital impedance measurement bridges with graphene-based ac quantum Hall resistance standards in a simplified cryogenic environment, to achieve simple, user-friendly quantum impedance standards suitable for primary realisation of impedance units in national metrology institutes, calibration centers, and the industry.
|
|
| 4. |
- Cedergren, Jan, et al.
(författare)
-
Inducible nitric oxide synthase is expressed in synovial fluid granulocytes
- 2002
-
Ingår i: Clinical Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 130, s. 150-155
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of the study was to evaluate the NO-producing potential of synovial fluid (SF) cells. SF from 15 patients with arthritis was compared with blood from the same individuals and with blood from 10 healthy controls. Cellular expression of inducible nitric oxide synthase (iNOS) was analysed by flow cytometry. High-performance liquid chromatography was used to measure L-arginine and L-citrulline. Nitrite and nitrate were measured colourimetrically utilizing the Griess' reaction. Compared to whole blood granulocytes in patients with chronic arthritis, a prominent iNOS expression was observed in SF granulocytes (P < 0.001). A slight, but statistically significant, increase in iNOS expression was also recorded in lymphocytes and monocytes from SF. L-arginine was elevated in SF compared to serum (257 ± 78 versus 176 ± 65 µmol/l, P = 0.008), whereas a slight increase in L-citrulline (33 ± 11 versus 26 ± 9 µmol/l), did not reach statistical significance. Great variations but no significant differences were observed comparing serum and SF levels of nitrite and nitrate, respectively, although the sum of nitrite and nitrate tended to be elevated in SF (19.2 ± 20.7 versus 8,6 ± 6.5 µmol/l,P = 0.054). Synovial fluid leucocytes, in particular granulocytes, express iNOS and may thus contribute to intra-articular NO production in arthritis.
|
|
| 5. |
- Cedergren, Jan, et al.
(författare)
-
Inducible nitric oxide synthase (NOS II) is constitutive in human neutrophils
- 2003
-
Ingår i: APMIS. - : Wiley. - 0903-4641 .- 1600-0463. ; 111:10, s. 963-968
-
Tidskriftsartikel (refereegranskat)abstract
- The objective was to study the expression of inducible nitric oxide synthase (NOS II) in and NO production by human blood neutrophils and in in vivo exudated neutrophils. Cellular expression of NOS II was evaluated by flow cytometry in whole blood, in isolated blood neutrophils, and in neutrophils obtained by exudation in vivo into skin chambers. Neutrophil NOS II was also demonstrated by Western blotting. Uptake of 3H-labelled L-arginine was studied in vitro and NOS activity measured in a whole cell assay by the conversion of 3H-arginine to 3H-citrulline. In contrast to unseparated blood cells, NOS II was demonstrable both in isolated blood neutrophils and exudated cells. The failure to detect NOS II by flow cytometry in whole blood cells thus proved to be due to the quenching effect of hemoglobin. Western blotting revealed a 130 kD band corresponding to NOS II in isolated blood neutrophils, but detection was dependent on diisopropylfluorophosphate for proteinase inhibition. L-arginine was taken up by neutrophils, but enzymatic activity could not be demonstrated. We conclude that human neutrophils constitutively express NOS II, but that its demonstration by FITC-labelling is inhibited by hemoglobin-mediated quenching in whole blood samples.
|
|
| 6. |
- Cedergren, Jan, et al.
(författare)
-
Intracellular oxidative activation in synovial fluid neutrophils from patients with rheumatoid arthritis but not from other arthritis patients
- 2007
-
Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 34:11, s. 2162-2170
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare total and intracellular oxidative activation of blood and synovial fluid (SF) neutrophils from patients with rheumatoid arthritis (RA) and other arthritides with blood donor neutrophils. Methods: Peripheral blood and SF samples were obtained from 26 gonarthritis patients (13 RA, 13 non-RA) attending the rheumatology unit for therapeutic joint aspiration. Isolated neutrophils were stimulated by a formylated tripeptide (fMLF) or by microbeads coated with collagen-I. Formation of superoxide-anion-derived reactive oxygen species (ROS) was studied by luminol-enhanced chemiluminescence. Paired samples of blood and SF neutrophils from patients with active arthritis were compared with blood neutrophils from patients in remission and from 47 healthy blood donors. Results: SF neutrophils from patients with RA, but not from non-RA patients, showed high baseline intracellular ROS production. Blood neutrophils from arthritis patients in remission existed in a primed state as revealed by more rapid oxidative response after collagen-bead challenge and a more pronounced response after fMLF stimulation compared to healthy blood donors. Blood neutrophils from RA patients with ongoing gonarthritis, however, did not differ from healthy blood donors concerning oxidative activation, whereas blood neutrophils from non-RA patients with gonarthritis showed a significantly lower peak ROS production. Conclusions: A novel finding with pathogenetic implications in our study is that SF neutrophils from patients with RA, but not other arthritides, are activated and produce ROS intracellularly. This implies that synovial neutrophils in RA are engaged in the processing of endocytosed material.
|
|
| 7. |
|
|
| 8. |
- Cedergren, Jan, 1965-
(författare)
-
Radical aspects on arthritis : the role of neutrophil generation of nitric oxide and superoxide in inflammatory conditions
- 2007
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The polymorphonuclear neutrophil granulocytes (neutrophils) are gaining renewed interest regarding their involvement in chronic inflammatory disorders, including rheumatoid arthritis (RA). Besides phagocytic and destructive capabilities, neutrophils have regulatory roles, e.g. by influencing responses from dendritic cells and lymphocytes. Several animal models have revealed that neutrophils are crucial for the initiation and maintenance of chronic inflammatory diseases. Neutrophil function is highly dependent on their ability to produce superoxide, an oxygen radical which can be further metabolized to other free radicals. Whether or not neutrophils are capable of producing the oxygen radical nitric oxide (NO˙) has been a matter of debate.In this thesis it was shown that freshly isolated neutrophils from the joint cavity of patients with RA, but not from other arthritis patients, had ongoing intracellular production of superoxide, indicating the processing of ingested material.The finding that joint neutrophils, but seemingly not circulating cells, expressed the NO-inducing enzyme iNOS, led to a series of experiments aimed to elucidate where in the exudative process this enzyme could first be detected. We could finally, for the first time, present evidence that human neutrophils actually express iNOS constitutively. Our data also suggest that neutrophil iNOS may be membrane associated, thus differing from the cytosolic location in other cell types. Since NOS activity was not demonstrated in isolated cells, the notion that neutrophil iNOS is regulated primarily at the transcriptional level must be questioned. NO production from iNOS requires the presence of its substrate, L-arginine. To test the hypothesis that neutrophil arginase prevents neutrophil NO-production, we investigated whether arginase inhibition affects neutrophil NO-dependent oxidative function. Initial data revealed a difference in the effect of arginase inhibition comparing neutrophil stimulus with a soluble formylated tri-peptide (fMLF) and integrin-mediated stimulation with particle-bound collagen type-1. This led to the hypothesis that integrin-ligation on neutrophils induces extracellular liberation of arginase, which was confirmed both by measuring arginase and its enzyme activity. The findings in this thesis may be important not only regarding the role of neutrophils in chronic joint inflammation, but also as a link in the accelerated atherosclerosis observed in chronic inflammatory disorders, e.g. RA.
|
|
| 9. |
- Cedergren, Marie, et al.
(författare)
-
Hyperemesis gravidarum that requires hospitalization and the use of antiemetic drugs in relation to maternal body composition
- 2008
-
Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 198:4
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The purpose of this study was to assess whether maternal prepregnancy body mass index was associated with the use of antiemetic drugs in early pregnancy and/or with the occurrence of hyperemesis gravidarum. STUDY DESIGN: A retrospective, population-based, cohort study. Women who delivered singleton infants (n = 749,435) from 19952003 were evaluated concerning the use of antiemetic drugs in early pregnancy (data available from 1995). Women who delivered singleton infants (n = 942,894) from 1992-2001 were evaluated concerning hospitalization because of hyperemesis gravidarum (data available until 2001). Adjusted odds ratios were determined by Mantel- Haenszel technique and were used as estimates of relative risk (RR). RESULTS: Underweight pregnant women were more likely to use antiemetic drugs (RR, 1.19, 95% CI, 1.14-1.24) and to become hospitalized for hyperemesis gravidarum (RR, 1.43, 95% CI, 1.33-1.54) compared with ideal weight women. Obese women were less likely to use antiemetic drugs (RR, 0.93, 95% CI, 0.89-0.97) and less likely to require hospitalization because of hyperemesis (RR, 0.90, 95% CI, 0.85-0.95) compared with women with an ideal body mass index. CONCLUSION: The use of antiemetic drugs and the occurrence of hyperemesis gravidarum are related to maternal body composition.
|
|
| 10. |
- Claesson, Ing-Marie, et al.
(författare)
-
Consumer satisfaction with a weight-gain intervention programme for obese pregnant women
- 2008
-
Ingår i: Midwifery. - : Elsevier. - 0266-6138 .- 1532-3099. ; 24:2, s. 163-167
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: to investigate women's attitudes and satisfaction with a weight-gain intervention programme during pregnancy.Design: exploratory, descriptive study. Data were collected via interviews.Setting: University hospital.Participants: 56 obese pregnant women who attended antenatal care at the University Hospital of Linkoping's obstetrical department and took part in an intervention programme aimed at reducing weight gain during pregnancy, between November 2003 and August 2004.Findings: the interviews comprised several questions concerning attitudes and opinions of the programme. Most of the women expressed positive experiences with the treatment and would attend the programme if they became pregnant again. Most of the women stated that they had changed their eating and exercise habits during pregnancy, and almost all of them had continued with these new habits. Even though the weight gain goal of a maximum 6.9 kg was reached by less than half of the participants, most of the women were satisfied with their weight gain. A total of 71.4% of the women participated in aqua aerobics classes. They stated that they were most satisfied with this form of exercise, and that it also was a good social experience.Key conclusions and implications for practice: a pregnant woman herself must be actively involved in setting her own goals to prevent excessive weight gain during pregnancy. Considerable effort and support must be placed on discussing strategies, pitfalls and risks. In order for the woman to maintain the change in attitude and habits, she must probably be given continuous feedback and reinforcement over the long term.
|
|
