| 1. |
- Abat, E., et al.
(författare)
-
Study of the response of the ATLAS central calorimeter to pions of energies from 3 to 9 GeV
- 2009
-
Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002 .- 1872-9576. ; 607:2, s. 372-386
-
Tidskriftsartikel (refereegranskat)abstract
- A fully instrumented slice of the ATLAS central detector was exposed to test beams from the SPS (Super Proton Synchrotron) at CERN in 2004. in this paper, the response of the central calorimeters to pions with energies in the range between 3 and 9 GeV is presented. The linearity and the resolution of the combined calorimetry (electromagnetic and hadronic calorimeters) was measured and compared to the prediction of a detector simulation program using the toolkit Geant 4. (C) 2009 Elsevier B.V. All rights reserved.
|
|
| 2. |
|
|
| 3. |
- Stozhkov, Y. I., et al.
(författare)
-
About Separation of Hadron and Electromagnetic Cascades in the Pamela Calorimeter
- 2005
-
Ingår i: International Journal of Modern Physics A. - 0217-751X .- 1793-656X. ; 20:29, s. 6745-6748
-
Tidskriftsartikel (refereegranskat)abstract
- Results of calibration of the PAMELA instrument at the CERN facilities are discussed. In September, 2003, the calibration of the Neutron Detector together with the Calorimeter was performed with the CERN beams of electrons and protons with energies of 20-180 GeV. The implementation of the Neutron Detector increases a rejection factor of hadrons from electrons about ten times. The results of calibration are in agreement with calculations.
|
|
| 4. |
- Casolino, M., et al.
(författare)
-
Cosmic-ray observations of the heliosphere with the PAMELA experiment
- 2006
-
Ingår i: Astrophysics. - : Elsevier BV. ; , s. 1848-1852
-
Konferensbidrag (refereegranskat)abstract
- The PAMELA experiment is a multi-purpose apparatus built around a permanent magnet spectrometer, with the main goal of studying in detail the antiparticle component of cosmic rays. The apparatus will be carried in space by means of a Russian satellite, due to launch in 2005, for a three year-long mission. The characteristics of the detectors composing the instrument, alongside the long lifetime of the mission and the orbital characteristics of the satellite, will allow to address several items of cosmic-ray physics. In this paper, we will focus on the solar and heliospheric observation capabilities of PAMELA.
|
|
| 5. |
|
|
| 6. |
- Lumbreras, B., et al.
(författare)
-
Meat intake and bladder cancer in a prospective study: a role for heterocyclic aromatic amines?
- 2008
-
Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 19:6, s. 649-656
-
Tidskriftsartikel (refereegranskat)abstract
- Objective The suspect carcinogens, heterocyclic amines (HAAs), found in well-done meat require host-mediated metabolic activation before inducing DNA mutations. The role of SULT1A1 and of NAT2 on the activation of HAAs suggests that NAT2 rapid acetylator genotype and SULT1A1 allele variants can have an effect on HAA carcinogenicity. Methods Data were collected as part of a case-control study nested within the EPIC cohort, the Gen Air investigation. EPIC is a prospective study designed to investigate the relationship between nutrition and cancer. Information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire. The subjects were restricted to non-smokers. We calculated the matched odds ratio for bladder cancer risk using logistic regression, controlling for potential confounders. Results There were 227 bladder cases and 612 controls matched 1:3. Meat intake and NAT2 genotype were not independently associated with bladder cancer risk. A significant relationship was observed between bladder cancer risk and consumption of meat only among subjects with the rapid NAT2 genotype (odds ratios [OR] 2.9, 95% CI 1.0-7.9 for the 2nd quartile of meat intake; 3.6, 95% CI 1.3-9.7 for the 3rd quartile; and 3.5, 95% CI 1.2-9.7 for the 4th quartile), and was not present among subjects with the slow genotype. An interaction between NAT2 and meat intake was found in logistic regression (P = 0.034). No association was observed for SULT1A *1/2 genotype (1.0; 95% CI 0.7-1.5) and for SULT1A1 *2/2 genotype (0.9; 95% CI 0.5-1.7). Conclusions These results are suggestive of a role of meat intake and NAT2 on bladder cancer risk. They support the hypothesis that among subjects with the rapid NAT2 acetylation genotype higher levels of HAAs exposure are a bladder cancer risk factor. We did not observe an effect of SULT1A1 allele variants on this cancer. The present study adds new information on the possible long-term adverse effects of diets with high meat intake.
|
|
| 7. |
- Manuguerra, M., et al.
(författare)
-
Multi-factor dimensionality reduction applied to a large prospective investigation on gene-gene and gene-environment interactions
- 2007
-
Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 28:2, s. 414-422
-
Tidskriftsartikel (refereegranskat)abstract
- It is becoming increasingly evident that single-locus effects cannot explain complex multifactorial human diseases like cancer. We applied the multi-factor dimensionality reduction (MDR) method to a large cohort study on gene-environment and gene-gene interactions. The study (case-control nested in the EPIC cohort) was established to investigate molecular changes and genetic susceptibility in relation to air pollution and environmental tobacco smoke (ETS) in non-smokers. We have analyzed 757 controls and 409 cases with bladder cancer (n = 124), lung cancer (n = 116) and myeloid leukemia (n = 169). Thirty-six gene variants (DNA repair and metabolic genes) and three environmental exposure variables (measures of air pollution and ETS at home and at work) were analyzed. Interactions were assessed by prediction error percentage and cross-validation consistency (CVC) frequency. For lung cancer, the best model was given by a significant gene-environment association between the base excision repair (BER) XRCC1-Arg399Gln polymorphism, the double-strand break repair (DSBR) BRCA2-Asn372His polymorphism and the exposure variable 'distance from heavy traffic road', an indirect and robust indicator of air pollution (mean prediction error of 26%, P < 0.001, mean CVC of 6.60, P = 0.02). For bladder cancer, we found a significant 4-loci association between the BER APE1-Asp148Glu polymorphism, the DSBR RAD52-3'-untranslated region (3'-UTR) polymorphism and the metabolic gene polymorphisms COMT-Val158Met and MTHFR-677C > T (mean prediction error of 22%, P < 0.001, mean CVC consistency of 7.40, P < 0.037). For leukemia, a 3-loci model including RAD52-2259C > T, MnSOD-Ala9Val and CYP1A1-Ile462Val had a minimum prediction error of 31% (P < 0.001) and a maximum CVC of 4.40 (P = 0.086). The MDR method seems promising, because it provides a limited number of statistically stable interactions; however, the biological interpretation remains to be understood.
|
|
| 8. |
- Vineis, P., et al.
(författare)
-
Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers
- 2007
-
Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 18:7, s. 1230-1242
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We chose a set of candidate single nucleotide polymorphisms (SNPs) to investigate gene-environment interactions in three types of cancer that have been related to air pollution (lung, bladder and myeloid leukemia). Patients and methods: The study has been conducted as a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (409 cancer cases and 757 matched controls). We included never and ex-smokers. SNPs were in genes involved in oxidative stress, phase I metabolizing genes, phase 11 metabolizing genes and methylenetetrahydrofolate reductase (MTHFR). Results: The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33-3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73-37.3; homozygotes). Other statistically significant associations were found in subgroups defined by smoking habits (never or ex-smokers), environmental tobacco smoke or gender, with no obvious pattern. When gene variants were organized according to the three main pathways, the emerging picture was of a strong involvement of combined phase I enzymes in leukemia, with an OR of 5 (1.63-15.4) for those having three or more variant alleles. The association was considerably stronger for leukemias arising before the age of 55.
|
|
| 9. |
|
|
| 10. |
- Jenab, M, et al.
(författare)
-
Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition
- 2006
-
Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 95:3, s. 406-415
-
Tidskriftsartikel (refereegranskat)abstract
- Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR) = 0.53, 95% confidence intervals (CI) = 0.30-0.94, P(trend) = 0.006), zeaxanthin (OR = 0.39, 95% CI = 0.22-0.69, P(trend) = 0.005), retinol (OR = 0.55, 95% CI = 0.33-0.93, P(trend) = 0.005) and lipid-unadjusted alpha-tocopherol (OR = 0.59, 95% CI = 0.37-0.94, P(trend) = 0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR = 0.26, 95% CI = 0.11-0.65, P(trend) = 0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.
|
|
| 11. |
- Pischon, T., et al.
(författare)
-
General and Abdominal Adiposity and Risk of Death in Europe
- 2008
-
Ingår i: New England Journal of Medicine. - 0028-4793. ; 359:20, s. 2105-2120
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Previous studies have relied predominantly on the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) to assess the association of adiposity with the risk of death, but few have examined whether the distribution of body fat contributes to the prediction of death. METHODS We examined the association of BMI, waist circumference, and waist-to-hip ratio with the risk of death among 359,387 participants from nine countries in the European Prospective Investigation into Cancer and Nutrition (EPIC). We used a Cox regression analysis, with age as the time variable, and stratified the models according to study center and age at recruitment, with further adjustment for educational level, smoking status, alcohol consumption, physical activity, and height. RESULTS During a mean follow-up of 9.7 years, 14,723 participants died. The lowest risks of death related to BMI were observed at a BMI of 25.3 for men and 24.3 for women. After adjustment for BMI, waist circumference and waist-to-hip ratio were strongly associated with the risk of death. Relative risks among men and women in the highest quintile of waist circumference were 2.05 (95% confidence interval [CI], 1.80 to 2.33) and 1.78 (95% CI, 1.56 to 2.04), respectively, and in the highest quintile of waist-to-hip ratio, the relative risks were 1.68 (95% CI, 1.53 to 1.84) and 1.51 (95% CI, 1.37 to 1.66), respectively. BMI remained significantly associated with the risk of death in models that included waist circumference or waist-to-hip ratio (P<0.001). CONCLUSIONS These data suggest that both general adiposity and abdominal adiposity are associated with the risk of death and support the use of waist circumference or waist-tohip ratio in addition to BMI in assessing the risk of death.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- van Gils, C H, et al.
(författare)
-
Consumption of vegetables and fruits and risk of breast cancer
- 2005
-
Ingår i: JAMA: The Journal of the American Medical Association. - 1538-3598. ; 293:2, s. 183-193
-
Tidskriftsartikel (refereegranskat)abstract
- Context The intake of vegetables and fruits has been thought to protect against breast cancer. Most of the evidence comes from case-control studies, but a recent pooled analysis of the relatively few published cohort studies suggests no significantly reduced breast cancer risk is associated with vegetable and fruit consumption. Objective To examine the relation between total and specific vegetable and fruit intake and the incidence of breast cancer. Design, Setting, and Participants Prospective study of 285526 women between the ages of 25 and 70 years, participating in the European Prospective Investigation Into Cancer and Nutrition (EPIC) study, recruited from 8 of the 10 participating European countries. Participants completed a dietary questionnaire in 1992-1998 and were followed up for incidence of cancer until 2002. Main Outcome Measures Relative risks for breast cancer by total and specific vegetable and fruit intake. Analyses were stratified by age at recruitment and study center. Relative risks were adjusted for established breast cancer risk factors. Results During 1486402 person-years (median duration of follow-up, 5.4 years), 3659 invasive incident breast cancer cases were reported. No significant associations between vegetable or fruit intake and breast cancer risk were observed. Relative risks for the highest vs the lowest quintile were 0.98 (95% confidence interval [CI], 0.84-1.14) for total vegetables, 1.09 (95% Cl, 0.94-1.25) for total fruit, and 1.05 (95% Cl, 0.92-1.20) for fruit and vegetable juices. For 6 specific vegetable subgroups no associations with breast cancer risk were observed either. Conclusion Although the period of follow-up is limited for now, the results suggest that total or specific vegetable and fruit intake is not associated with risk for breast cancer.
|
|
| 15. |
- Aad, G., et al.
(författare)
-
The ATLAS Experiment at the CERN Large Hadron Collider
- 2008
-
Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08003
-
Forskningsöversikt (refereegranskat)abstract
- The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
|
|
| 16. |
- Al-Delaimy, WK, et al.
(författare)
-
Plasma carotenoids as biomarkers of intake of fruits and vegetables: individual-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2005
-
Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 59:12, s. 1387-1396
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim in this study was to assess the association between individual plasma carotenoid levels (alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, lutein, zeaxanthin) and fruit and vegetable intakes recorded by a calibrated food questionnaire (FQ) and 24- h dietary recall records (24HDR) in nine different European countries with diverse populations and widely varying intakes of plant foods. Design: A stratified random subsample of 3089 men and women from nine countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had provided blood samples and dietary and other lifestyle information between 1992 and 2000, were included. Results: beta-Cryptoxanthin was most strongly correlated with total fruits (FQ r = 0.52, 24HDR r = 0.39), lycopene with tomato and tomato products (FQ r = 0.38, 24HDR r = 0.25), and alpha-carotene with intake of root vegetables (r = 0.39) and of total carrots (r = 0.38) for FQ only. Based on diet measured by FQ and adjusting for possible confounding by body mass index (BMI), age, gender, smoking status, alcohol intake, and energy intake, the strongest predictors of individual plasma carotenoid levels were fruits (R-partial(2) = 17.2%) for beta-cryptoxanthin, total carrots (R-partial(2) = 13.4%) and root vegetables (R-partial(2) = 13.3%) for alpha-carotene, and tomato products (R-partial(2) = 13.8%) for lycopene. For 24HDR, the highest R-partial(2) was for fruits in relation to beta-cryptoxanthin (7.9%). Conclusions: Intakes of specific fruits and vegetables as measured by food questionnaires are good predictors of certain individual plasma carotenoid levels in our multicentre European study. At individual subject levels, FQ measurements of fruits, root vegetables and carrots, and tomato products are, respectively, good predictors of beta-cryptoxanthin, alpha-carotene, and lycopene in plasma.
|
|
| 17. |
- Besson, H., et al.
(författare)
-
A cross-sectional analysis of physical activity and obesity indicators in European participants of the EPIC-PANACEA study
- 2009
-
Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 33:4, s. 497-506
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Cross-sectional data suggest a strong association between low levels of physical activity and obesity. The EPIC-PANACEA ( European Prospective Investigation into Cancer-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating out of home And obesity) project was designed to investigate the associations between physical activity and body mass index (BMI) and waist circumference based on individual data collected across nine European countries. Methods: In the European Prospective Investigation into Cancer and Nutrition ( EPIC), 519 931 volunteers were recruited between 1992 and 2000, of whom 405 819 had data on main variables of interest. Height, body weight and waist circumference were measured using standardized procedures. Physical activity was assessed using a validated four-category index reflecting a self-reported usual activity during work and leisure time. The associations between physical activity and BMI and waist circumference were estimated using multilevel mixed effects linear regression models, adjusted for age, total energy intake, smoking status, alcohol consumption and educational level. Results: A total of 125 629 men and 280 190 women with a mean age of 52.9 (s.d. 9.7) and 51.5 (s.d. 10.0) years, respectively were included. The mean BMI was 26.6 kg/m(2) (s.d. 3.6) in men and 25.0 kg/m(2) (s.d. 4.5) in women. Fifty percent of men and 30% of women were categorized as being active or moderately active. A one-category difference in the physical activity index was inversely associated with a difference of 0.18 kg/m(2) in the mean BMI (95% confidence interval, CI, 0.11, 0.24) and 1.04-cm (95% CI 0.82, 1.26) difference in waist circumference in men. The equivalent figures for women were 0.31 kg/m(2) (95% CI 0.23, 0.38) and 0.90 cm ( 95% CI 0.71, 1.08), respectively. Conclusions: Physical activity is inversely associated with both BMI and waist circumference across nine European countries. Although we cannot interpret the association causally, our results were observed in a large and diverse cohort independently from many potential confounders.
|
|
| 18. |
|
|
| 19. |
- Mendez, M. A., et al.
(författare)
-
Cereal fiber intake may reduce risk of gastric adenocarcinomas: The EPIC-EURGAST study
- 2007
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:7, s. 1618-1623
-
Tidskriftsartikel (refereegranskat)abstract
- Numerous case-control studies suggest dietary fiber may reduce risk of gastric cancer, but this has not been confirmed prospectively. A previous case-control study reported reduced risk of gastric cardia adenocarcinomas associated with cereal fiber, but not with fruit or vegetable fiber. To date, different food sources of fiber have not been examined with respect to noncardia tumors or diverse histologic sub-types. This study prospectively examines associations between fiber from different food sources and incident gastric adenocarcinomas (GC) among more than 435,000 subjects from 10 countries participating in the European Prespective Investigation into Cancer and Nutrition study. Subjects aged 25-70 years completed dietary questionnaires in 1992-98, and were followed up for a median of 6.7 years. About 312 incident GCs were observed. The relative risk of GC was estimated based on cohort-wide sex-specific fiber intake quartiles using proportional hazards models to estimate hazards ratios (HRs) and 95% confidence intervals (CIs). Intakes of cereal fiber, but not total, fruit or vegetable fiber, were associated with reduced GC risk [adjusted HR for the highest vs. lowest quartile of cereal fiber 0.69, 0.48-0.99]. There was a strong inverse association for diffuse [HR 0.43, 0.22-0.86], but not intestinal type [HR 0.98, 0.54-1.80] tumors. Associations for cardia vs. noncardia tumors were similar to those for overall GC, although cardia associations did not reach significance. Cereal fiber consumption may help to reduce risk of GC, particularly diffuse type tumors. Further study on different food sources of fiber in relation to GC risk is warranted to confirm these relationships.
|
|
| 20. |
- Nielsen, Peter, et al.
(författare)
-
Multi-level Theoretical Framework – Meadow Background document no1
- 2009
-
Ingår i: Meadow reports. ; 1, s. 1-59
-
Forskningsöversikt (refereegranskat)abstract
- This report is one outcome of workpackage 2 in the EU funded MEADOW project. Its aim has been to establish an overview of theoretical literature in surveys on organisational change, innovation and work conditions. An international team of scholars have cooperated on this task. Scholars from Aalborg University (Denmark) have coordinated the workpackage and accepted responsibility for establishing a comprehensive multilevel framework regarding theories on organisational change, innovation and work conditions.
|
|
| 21. |
- Orfanos, P, et al.
(författare)
-
Eating out of home and its correlates in 10 European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC) study
- 2007
-
Ingår i: Public Health Nutrition. - 1475-2727 .- 1368-9800. ; 10:12, s. 1515-1525
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare the average out-of-home (OH) consumption of foods and beverages, as well as energy intake, among populations from 10 European countries and to describe the characteristics of substantial OH eaters, as defined for the purpose of the present study, in comparison to other individuals. DESIGN: Cross-sectional study. Dietary data were collected through single 24-hour dietary recalls, in which the place of consumption was recorded. For the present study, substantial OH eaters were defined as those who consumed more than 25% of total daily energy intake at locations other than the household premises. Mean dietary intakes and the proportion of substantial OH eaters are presented by food group and country. Logistic regression analyses were used to estimate the odds of being a substantial OH eater in comparison to not being one, using mutually adjusted possible non-dietary determinants. SETTING: Ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS: The subjects were 34 270 individuals, 12 537 men and 21 733 women, aged 35-74 years. RESULTS: The fraction of energy intake during OH eating was generally higher in northern European countries than in the southern ones. Among the food and beverage groups, those selectively consumed outside the home were coffee/tea/waters and sweets and, to a lesser extent, cereals, meats, added lipids and vegetables. Substantial OH eating was positively associated with energy intake and inversely associated with age and physical activity. Substantial OH eating was less common among the less educated compared with the more educated, and more common during weekdays in central and north Europe and during the weekend in south Europe. CONCLUSIONS: Eating outside the home was associated with sedentary lifestyle and increased energy intake; it was more common among the young and concerned in particular coffee/tea/waters and sweets.
|
|
| 22. |
- Pass, Jesper, et al.
(författare)
-
Murine monoclonal antibodies against murine uPA receptor produced in gene-deficient mice: inhibitory effects on receptor-mediated uPA activity in vitro and in vivo
- 2007
-
Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 97:6, s. 1013-1022
-
Tidskriftsartikel (refereegranskat)abstract
- Binding of urokinase plasminogen activator (uPA) to its cellular receptor, uPAR, potentiates plasminogen activation and localizes it to the cell surface. Focal plasminogen activation is involved in both normal and pathological tissue remodeling processes including cancer invasion. The interaction between uPA and uPAR therefore represents a potential target for anti-invasive cancer therapy. Inhibitors of the human uPA-uPAR interaction have no effect in the murine system. To enable in-vivo studies in murine cancer models we have now generated murine monoclonal antibodies (mAbs) against murine uPAR (muPAR) by immunizing uPAR-deficient mice with recombinant muPAR and screened for antibodies, which inhibit the muPA-muPAR interaction. Two of the twelve mAbs obtained, mR1 and mR2, interfered with the interaction between muPAR and the amino-terminal fragment of muPA (mATF) when analyzed by surface plasmon resonance. The epitope for mR1 is located on domain I of muPAR, while that of mR2 is on domains (II-III). In cell binding experiments using radiolabelled mATF, the maximal inhibition obtained with mR1 was 85% while that obtained with mR2 was 50%. The IC(50) value for mR1 was 0.67 nM compared to 0.14 nM for mATF. In an assay based on modified anthrax toxins, requiring cell-bound muPA activity for its cytotoxity, an approximately 50% rescue of the cells could be obtained by addition of mR1. Importantly, in-vivo efficacy of mR1 was demonstrated by the ability of mR1 to rescue mice treated with a lethal dose of uPA-activatable anthrax toxins.
|
|
| 23. |
|
|
| 24. |
- Agudo, Antonio, et al.
(författare)
-
Polymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition
- 2006
-
Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 15:12, s. 2427-2434
-
Tidskriftsartikel (refereegranskat)abstract
- Metabolizing enzymes, which often display genetic polymorphisms, are involved in the activation of compounds present in tobacco smoke that may be relevant to gastric carcinogenesis. We report the results of a study looking at the association between risk of gastric adenocarcinoma and polymorphisms in genes CYP1A1, CYP1A2, EPHX1, and GSTT1. A nested case-control study was carried out within the European Prospective Investigation into Cancer and Nutrition, developed in 10 European countries. The study includes 243 newly diagnosed cases of histologically confirmed gastric adenocarcinoma and 946 controls matched by center, age, sex, and date of blood collection. Genotypes were determined in nuclear DNA from WBCs. We found an increased risk of gastric cancer for homozygotes for C (histidine) variant in Y113H of EPHX1 (odds ratio, 1.91; 95% confidence interval, 1.19-3.07) compared with subjects with TC/TT. There was also a significant increased risk for smokers carrying at least one variant allele A in Ex7+129C > A (m4) of CYP1A1 and never smokers with null GSTT1 and allele A in the locus -3859G > A of CYP1A2. Most of these genes are involved in the activation and detoxification of polycyclic aromatic hydrocarbons, suggesting a potential role of these compounds in gastric carcinogenesis.
|
|
| 25. |
|
|
| 26. |
- Al-Delaimy, WK, et al.
(författare)
-
Plasma carotenoids as biomarkers of intake of fruits and vegetables: ecological-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2005
-
Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 59:12, s. 1397-1408
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to assess the ability of a single 24-h dietary recall (24HDR) and food questionnaires (FQ) to predict plasma carotenoid levels at the ecological level by assessing the relationship between mean plasma carotenoid levels and mean intake of fruit and vegetables measured by 24HDR and FQ across 16 European regions. Design: A random subsample of 3089 subjects was included, stratified by age and gender. They provided blood samples and dietary information between 1992 and 2000 as part of the European Prospective Investigation into Cancer and Nutrition. Results: Using Spearman's correlation coefficients, the correlations between mean regional 24HDR fruit and vegetable variables and corresponding mean plasma carotenoid levels were generally higher than the correlations using FQ means. The highest correlation was between the 24HDR citrus fruit variable and beta-cryptoxanthin (r = 0.90). For 24HDR, total fruits and vegetables were highly correlated with lutein, zeaxanthin, and beta-cryptoxanthin (r = 0.83-0.87), while vegetables were more closely related with lutein (r = 0.69) and zeaxanthin (r = 0.68), and fruits correlated with zeaxanthin (r = 0.87) and beta-cryptoxanthin (r = 0.84). Root vegetables (r = 0.81) and total carrots (r = 0.71) were well correlated with alpha-carotene. In the multivariate models adjusting for age, body mass index, and season, and using observations of means stratified by sex and region, the association was generally higher for 24HDR compared to FQ. Conclusion: Mean regional intakes of fruits and vegetables in several European countries were closely correlated with corresponding mean plasma levels of individual carotenoids. Fruits and vegetables measured by 24HDR were generally better able to predict plasma carotenoids at the ecological level.
|
|
| 27. |
- Axelsson, Susanna, et al.
(författare)
-
Disseminating evidence from health technology assessment : the case of tobacco prevention
- 2006
-
Ingår i: International Journal of Technology Assessment in Health Care. - Stockholm : Karolinska Institutet, Dept of Public Health Sciences. - 0266-4623.
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aims of the present study were to investigate the awareness among dentists and dental hygienists of evidence-based reports and guidelines on tobacco cessation activities and the impact these publications had on clinical practice. METHODS: A questionnaire was mailed to dental hygienists and dentists in Stockholm County, Sweden, and the results were compared with a previous investigation. RESULTS: Among the respondents, awareness of a popular science version of a systematic review on smoking and its effect on oral health was reported by 90 percent of the hygienists and 66 percent of the dentists. The information was used in clinical work by 34 percent of the dentists and 54 percent of the hygienists. Reported changes in patterns of practice were more frequent recommendations to use nicotine replacement therapy and a more widespread use of setting quit dates. Approximately one quarter of the dental professionals reported that they had increased tobacco cessation consultation because of the results from the reports. CONCLUSIONS: Changes in patterns of practice were observed after dissemination of evidence-based information on tobacco cessation. Methods that were proven to be effective in the evidence-based report such as discussing quit dates and recommending nicotine replacement therapy were more commonly used after the publication of the report. Short, popular versions of extensive systematic reviews seem to be useful for implementing evidence-based knowledge and changing clinical practice.
|
|
| 28. |
|
|
| 29. |
- Canzian, Federico, et al.
(författare)
-
Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3).
- 2009
-
Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 9, s. 257-
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gonadotropin releasing hormone (GNRH1) triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR) in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3). METHODS: We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs) were genotyped and used to identify haplotype-tagging SNPs (htSNPS) in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II), European Prospective Investigation on Cancer and Nutrition (EPIC), Multiethnic Cohort (MEC), Nurses' Health Study (NHS), and Women's Health Study (WHS). Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone) were also measured in 4713 study subjects. RESULTS: Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. CONCLUSION: Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.
|
|
| 30. |
- Capella, Gabriel, et al.
(författare)
-
DNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study
- 2008
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 1464-3685 .- 0300-5771. ; 37:6, s. 1316-1325
-
Tidskriftsartikel (refereegranskat)abstract
- Background The contribution of genetic variation in DNA repair genes to gastric cancer (GC) risk remains essentially unknown. The aim of this study was to explore the relative contribution of DNA repair gene polymorphisms to GC risk and severe chronic atrophic gastritis (SCAG). Method A nested case control study within the EPIC cohort was performed including 246 gastric adenocarcinomas and 1175 matched controls. Controls with SCAG (n 91), as defined by low pepsinogen A (PGA) levels, and controls with no SCAG (n 1061) were also compared. Twelve polymorphisms at DNA repair genes (MSH2, MLH1, XRCC1, OGG1 and ERCC2) and TP53 gene were analysed. Antibodies against Helicobacter pylori were measured. Results No association was observed for any of these polymorphisms with stomach cancer risk. However, ERCC2 K751Q polymorphism was associated with an increased risk for non-cardial neoplasm [odds ratio (OR) 1.78; 95 confidence interval (CI) 1.023.12], being ERCC2 K751Q and D312N polymorphisms associated with the diffuse type. ERCC2 D312N (OR 2.0; 95 CI 1.093.65) and K751Q alleles (OR 1.82; 95 CI 1.013.30) and XRCC1 R399Q (OR 1.69; 95 CI 1.022.79) allele were associated with an increased risk for SCAG. Conclusion Our study supports a role of ERCC2 in non-cardial GC but not in cardial cancer. A concordant result was observed for subjects with low PGA levels. XRCC1 allele was associated also with SCAG. This is the first prospective study suggesting that individual variation in DNA repair may be relevant for gastric carcinogenesis, a finding that will require further confirmation validation in larger independent studies.
|
|
| 31. |
- Casolino, M., et al.
(författare)
-
Launch of the space experiment PAMELA
- 2008
-
Ingår i: Advances in Space Research. - : Elsevier. - 0273-1177 .- 1879-1948. ; 42:3, s. 455-466
-
Tidskriftsartikel (refereegranskat)abstract
- PAMELA is a satellite borne experiment designed to study with great accuracy cosmic rays of galactic, solar, and trapped nature in a wide energy range (protons 80 MeV-700 GeV, electrons 50 MeV-400 GeV). Main objective is the study of the antimatter component: antiprotons (80 MeV-190 GeV), positrons (50 MeV-270 GeV) and search for antimatter with a precision of the order of 10-8. The experiment, housed on board the Russian Resurs-DK I satellite, was launched on June 15th, 2006 in a 350 x 600 km orbit with all inclination of 70'. The detector is composed of a series of scintillator counters arranged at the extremities of a permanent magnet spectrometer to provide charge, time-of-flight, and rigidity information. Lepton/hadron identification is performed by a silicon-tungsten calorimeter and a neutron detector placed at the bottom of the device. An anticounter system is used offline to reject false triggers coming from the satellite. In self-trigger mode the calorimeter, the neutron detector, and a shower tail catcher are capable of an independent measure of the lepton component up to 2 TeV. In this work we describe the experiment, its scientific objectives, and the performance in the first months after launch.
|
|
| 32. |
- Cust, Anne E., et al.
(författare)
-
Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2007
-
Ingår i: Endocrine-Related Cancer. - 1479-6821 .- 1351-0088. ; 14:3, s. 755-767
-
Tidskriftsartikel (refereegranskat)abstract
- To clarify the role of metabolic factors in endometrial carcinogenesis, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), and examined the relation between prediagnostic plasma lipids, lipoproteins, and glucose, the metabolic syndrome (MetS; a cluster of metabolic factors) and endometrial cancer risk. Among pre- and postmenopausal women, 284 women developed endometrial cancer during follow-up. Using risk set sampling, 546 matched control subjects were selected. From conditional logistic regression models, high-density lipoprotein cholesterol (HDL-C) levels were inversely associated with risk body mass index (BMI)-adjusted relative risk (FR) for top versus bottom quartile 0.61 (95% confidence intervals (CI) 0.38-0.97), P-trend= 0.02). Glucose levels were positively associated with risk (BMI-adjusted RR top versus bottom quartile 1.69 (95% Cl 0.99-2.90), P-trend, = 0.03), which appeared stronger among postmenopausal women (BMI-adjusted RR top versus bottom tertile 2.61 (95% Cl 1.46-4.66), P-trend=0.0006, P-heterogeneity=0.13) and never-users of exogenous hormones (P-heterogeneity=0-005 for oral contraceptive (OC) use and 0.05 for hormone replacement therapy-use). The associations of HDL-C and glucose with risk were no longer statistically significant after further adjustment for obesity-related hormones. Plasma total cholesterol, Low-density lipoprotein cholesterol (LDL-C), and triglycerides were not significantly related to overall risk. The presence of MetS was associated with risk (RR 2.12 (95% CI 1.51-2.97)), which increased with the number of MetS factors (P-trend=0.02). An increasing number of MetS factors other than waist circumference, however, was marginally significantly associated with risk only in women with waist circumference above the median (P-interaction=0-01). None of the associations differed significantly by fasting status. These findings suggest that metabolic abnormalities and obesity may act synergistically to increase endometrial cancer risk.
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
- Darby, Dennis, et al.
(författare)
-
The role of currents and sea ice in both slowly deposited central Arctic and rapidly deposited Chukchi-Alaskan margin sediments
- 2009
-
Ingår i: Global and Planetary Change. - : Elsevier BV. - 0921-8181 .- 1872-6364. ; 68:1-2, s. 58-72
-
Tidskriftsartikel (refereegranskat)abstract
- A study of three long cores from the outer shelf and continental slope north of Alaska in the Arctic Ocean indicate that localized drift deposits occur here with sedimentation rates of more than 1.5 m/kyr during the Holocene. Currents in this area average about 5–20 cm/s but can reach 100 cm/s and these velocities transport the sediment found in these cores primarily as intermittent suspended load. These high accumulation sediments form levee-like deposits associated with margins of canyons cutting across the shelf and slope. Unlike most textural investigations of Arctic sediment that focus on the coarser ice-rafted detritus (IRD), this paper focuses on the > 95% of the sediment, which is finer than 45 μm. The mean size of this fraction varies between 6 and 15 μm in Holocene sediments from the Chukchi–Alaskan shelf and slope with the higher values closer to shore. Analysis of detailed size distributions of these Holocene deposits are compared to 34 sediment samples collected from sea ice across the Arctic Ocean and to Holocene sediment from central Arctic Ocean cores and indicate that similar textural parameters occur in all of these sediments. Principal components of these size distributions indicate that sea ice is an important link between the shelves and the central Arctic. Factor scores indicate nearly identical components in the clay and fine silt size fractions but very different components in the coarse silt for sea ice sediment and central Arctic ridge sediments compared to shelf and continental slope deposits. Sea ice must contribute to sedimentation in both of these Arctic regions, but bottom currents dominate in the slope region, forming drift deposits.
|
|
| 36. |
- Di Mauro, A., et al.
(författare)
-
Development of innovative micro-pattern gaseous detectors with resistive electrodes and first results of their applications
- 2007
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 581:1-2, s. 225-231
-
Tidskriftsartikel (refereegranskat)abstract
- The paper summarizes our latest progress in the development of newly introduced micro-pattern gaseous detectors with resistive electrodes. These resistive electrodes protect the detector and the front-end electronics in case of occasional discharges and thus make the detectors very robust and reliable in operation. As an example, we describe in greater detail a recently developed GEM-like detector, fully spark-protected with electrodes made of resistive kapton. We discovered that all resistive layers used in these studies (including kapton) that are coated with photosensitive layers, such as CsI, can be used as efficient photocathodes for detectors operating in a pulse counting mode. There is a description of the first applications of such detectors combined with CsI or SbCs photocathodes for the detection of UV photons at room and cryogenic temperatures.
|
|
| 37. |
- Engeset, D, et al.
(författare)
-
Fish consumption and breast cancer risk. The European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2006
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 119:1, s. 175-182
-
Tidskriftsartikel (refereegranskat)abstract
- There is current interest in fish consumption and marine omega-3 (n-3) fatty acids and breast cancer risk. Some in vitro and animal studies have suggested an inhibitory effect of marine n-3 fatty acids on breast cancer growth, but the results from epidemiological studies that have examined the association between fish consumption and breast cancer risk in humans are inconsistent. We examined fish consumption and breast cancer risk in 310,671 women aged between 25 and 70 yr at recruitment into the European Prospective Investigation Into Cancer and Nutrition (EPIC). The participants completed a dietary questionnaire between 1992-98 and were followed up for incidence of breast cancer for a median of 6.4 yr. Hazard ratio for breast cancer by intake of total and lean and fatty fish were estimated, stratified by study centre and adjusted for established breast cancer risk factors. During follow-up, 4,776 invasive incident breast cancers were reported. No significant associations between intake of total fish and breast cancer risk were observed, hazard ratio (HR) 1.01 (95% confidence interval [CI] 0.99-1.02; p = 0.28 per 10 g fish/day). When examining lean and ratty fish separately, we round a positive significant association only in the highest quintile for fatty fish (HR 1.13, 95% CI 1.01-1.26), but test for trend was not significant (p = 0.10). No associations with breast cancer risk were observed when the study participants were subdivided by menopausal status. Although the period of follow-up is relatively short, the results provide no evidence for an association between fish intake and breast cancer risk. (c) 2006 Wiley-Liss, Inc.
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
- Jenab, M., et al.
(författare)
-
Dietary intakes of retinol, beta-carotene, vitamin D and vitamin E in the European Prospective Investigation into Cancer and Nutrition cohort
- 2009
-
Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 63:4s, s. 150-178
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To describe the intake of the fat-soluble nutrients retinol, beta-carotene, vitamin E and vitamin D and their food sources among 27 redefined centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: Between 1995 and 2000, 36 034 subjects (age range: 35-74 years) completed a single standardized 24-h dietary recall using a computerized interview software program (EPIC-SOFT). Intakes of the fat-soluble nutrients were estimated using the standardized EPIC Nutrient Database. Results: For all the nutrients, in most centres, men had a higher level of intake than did women, even after adjustments for total energy intake and anthropometric confounders. Distinct regional gradients from northern to southern European countries were observed for all nutrients. The level intake of beta-carotene and vitamin E also showed some differences by level of education, smoking status and physical activity. No meaningful differences in the nutrient intake were observed by age range. Conclusions: These results show differences by study centre, gender, age and various lifestyle variables in the intake of retinol, beta-carotene, vitamin E and vitamin D between 10 European countries. European Journal of Clinical Nutrition (2009) 63, S150-S178; doi: 10.1038/ejcn.2009.79
|
|
| 43. |
|
|
| 44. |
- Jögi, Annika, et al.
(författare)
-
Systemic administration of anti-urokinase plasminogen activator receptor monoclonal antibodies induces hepatic fibrin deposition in tissue-type plasminogen activator deficient mice
- 2007
-
Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 5:9, s. 1936-1944
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Degradation of extracellular matrix proteins, such as fibrin, is pivotal to tumor invasion. Inhibition of the interaction between urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and hence pro-u-PA activation, is an attractive approach to anti-invasive cancer therapy. A number of inhibitors exist for the human system, but because of species specificity none of these are efficient in mice. We have recently generated an inhibitory monoclonal antibody (mAb) against mouse u-PAR (mR1) by immunization of u-PAR-deficient mice. OBJECTIVES: To evaluate the effect of mR1 in vivo in a physiological setting sensitive to deregulated fibrinolysis, we have administered mR1 systemically and quantitated the effect on liver fibrin accumulation. METHODS: Wild-type and tissue-type plasminogen activator (t-PA) deficient mice were administered with mR1, or control antibody, during 6 weeks. Thereafter, the livers were retrieved and the amount of liver fibrin measured by unbiased morphometrical analysis of immunofluorescence signal. RESULTS: Systemic administration of mR1 caused significantly increased fibrin signal in anti-u-PAR treated t-PA-deficient mice compared to mock-treated, which mimics the phenotype of u-PAR;t-PA double-deficient mice. Fibrin and fibronectin accumulated within the sinusoidal space and was infiltrated by inflammatory cells. Analysis of small and rare hepatic fibrin plaques observed in t-PA-deficient mice showed infiltrating macrophages that, contrary to surrounding Kuppfer cells, expressed u-PAR. CONCLUSION: We show that u-PAR-expressing macrophages are involved in cell-mediated fibrinolysis of liver fibrin deposits, and that the antimouse-u-PAR mAb is effective in vivo and thus suited for studies of the effect of targeting the u-PA/u-PAR interaction in mouse cancer models.
|
|
| 45. |
|
|
| 46. |
- Linseisen, J., et al.
(författare)
-
Dietary fat intake in the European Prospective Investigation into Cancer and Nutrition: results from the 24-h dietary recalls
- 2009
-
Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 63:4s, s. 61-80
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: This paper describes the dietary intake of total fat, saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) and cholesterol of participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) in 27 centres across 10 countries. Methods: Between 1995 and 2000, a stratified random sample of 36 034 participants (age range 35-74 years) completed a standardized 24-h dietary recall, assessed by means of the computer software EPIC-SOFT. Lipid intake data were calculated using a standardized nutrient database. Results: On average, the contribution of fat to total energy intake was >= 34% of energy intake (% en) in women and >= 36% en in men for most EPIC centres, except for the British, Dutch and most Italian cohorts. Total fat (> 40% en) and MUFA intakes (21% en, mainly from olive oil) were highest in Greece. Except for the Greek, Spanish and Italian centres, the average MUFA intake ranged between 10 and 13% en, with a high proportion derived from animal sources. SFA intake in women and men was lowest in the Greek, Spanish, Italian and UK cohorts with an average of <= 13% en (down to 9% en), and highest in the Swedish centres (16% en). The mean PUFA intake was in the range of 4-8% en, being highest in the UK health-conscious cohort. The average cholesterol intake across EPIC varied from 140 to 384 mg/d in women and 215-583 mg/d in men. Conclusions: The presented data show differences and similarities in lipid intake across the European EPIC cohorts and also show differences in food sources of dietary lipids. European Journal of Clinical Nutrition (2009) 63, S61-S80; doi: 10.1038/ejcn.2009.75
|
|
| 47. |
- Liu, Kui, et al.
(författare)
-
Successful ovulation in plasminogen-deficient mice treated with the broad-spectrum matrix metalloproteinase inhibitor galardin.
- 2006
-
Ingår i: Developmental Biology. - New York : Academic P.. - 0012-1606 .- 1095-564X. ; 295:2, s. 615-622
-
Tidskriftsartikel (refereegranskat)abstract
- Many studies have suggested the hypothesis that the plasminogen activator (PA) system and the matrix metalloproteinase (MMP) system, either separately or in combination, may provide the proteolytic activity that is required for rupture of the follicular wall at the time of ovulation. Our recent studies on ovulation in plasminogen (plg)-deficient mice have, however, shown that plasmin is not required for normal ovulation, leading us to the hypothesis that MMPs may be a more important source of proteolysis for this process. To investigate the role of MMPs and also the possibility of a functional overlap or synergy between the MMP and PA systems during ovulation, we have studied ovulation efficiency in wild-type and plg-deficient mice treated with the broad-spectrum MMP inhibitor galardin. We found that in both wild-type mice and heterozygous plg-deficient (plg(+/-)) mice that had been treated with galardin prior to ovulation, there was a mild (18-20%) reduction in ovulation efficiency. Surprisingly, galardin treatment of plg-deficient (plg(-/-)) mice only caused an additional 14% reduction in ovulation efficiency as compared to vehicle-treated plg(-/-) mice. Our data therefore suggest that although MMPs may play a role in degradation of the follicular wall, they may not be obligatory for ovulation. In contrast to previous studies on tissue remodeling during wound heating and placental development, we have demonstrated that there is no obvious functional overlap or synergy between the PA and MMP systems, which has previously been thought to be essential for the ovulatory process.
|
|
| 48. |
- Lund, Anders, et al.
(författare)
-
Automatic fitting procedures for EPR spectra of disordered systems: matrix diagonalization and perturbation methods applied to fluorocarbon radicals
- 2008
-
Ingår i: Spectrochimica Acta Part A - Molecular and Biomolecular Spectroscopy. - : Elsevier. - 1386-1425 .- 1873-3557. ; 69:5, s. 1294-1300
-
Tidskriftsartikel (refereegranskat)abstract
- Two types of automatic fitting procedures for EPR spectra of disordered systems have been developed, one based on matrix diagonalisation of a general spin Hamiltonian, the other on 2nd order perturbation theory. The first program is based on a previous Fortran code complemented with a newly written interface in Java to provide user-friendly in- and output. The second is intended for the special case of free radicals with several relatively weakly interacting nuclei, in which case the general method becomes slow. A least squares’ fitting procedure utilizing analytical or numerical derivatives of the theoretically calculated spectrum with respect to the g-and hyperfine structure (hfs) tensors was used to refine those parameters in both cases. ‘Rigid limit’ ESR spectra from radicals in organic matrices and in polymers, previously studied experimentally at low temperature, were analysed by both methods. Fluoro-carbon anion radicals could be simulated, quite accurately with the exact method, whereas automatic fitting on e.g. the c-C4F8- anion radical is only feasible with the 2nd order approximative treatment. Initial values for the 19F hfs tensors estimated by DFT calculations were quite close to the final. For neutral radicals of the type XCF2CF2• the refinement of the hfs tensors by the exact method worked better than the approximate. The reasons are discussed. The ability of the fitting procedures to recover the correct magnetic parameters of disordered systems was investigated by fittings to synthetic spectra with known hfs tensors. The exact and the approximate methods are concluded to be complementary, one being general, but limited to relatively small systems, the other being a special treatment, suited for S=½ systems with several moderately large hfs.
|
|
| 49. |
- Lund Hansen, Anders, et al.
(författare)
-
Smith, Neil
- 2009
-
Ingår i: International Encyclopedia of Human Geography. - 9780080449104 ; 10, s. 163-164
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 50. |
- Lund, Nicole, et al.
(författare)
-
The human P-k histo-blood group antigen provides protection against HIV-1 infection
- 2009
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 113:20, s. 4980-4991
-
Tidskriftsartikel (refereegranskat)abstract
- Several human histo-blood groups are glycosphingolipids, including P/P1/P-k. Glycosphingolipids are implicated in HIV-host-cell-fusion and some bind to HIV-gp120 in vitro. Based on our previous studies on Fabry disease, where P-k accumulates and reduces infection, and a soluble P-k analog that inhibits infection, we investigated cell surface-expressed P-k in HIV infection. HIV-1 infection of peripheral blood-derived mononuclear cells (PBMCs) from otherwise healthy persons, with blood group P-1(k), where P-k is overexpressed, or blood group p, that completely lacks P-k, were compared with draw date-matched controls. Fluorescence-activated cell sorter analysis and/or thin layer chromatography were used to verify P-k levels. P-1(k) PBMCs were highly resistant to R5 and X4 HIV-1 infection. In contrast, p PBMCs showed 10- to 1000-fold increased susceptibility to HIV-1 infection. Surface and total cell expression of P-k, but not CD4 or chemokine coreceptor expression, correlated with infection. Pk liposome-fused cells and CD4(+) HeLa cells manipulated to express high or low P-k levels confirmed a protective effect of P-k. We conclude that P-k expression strongly influences susceptibility to HIV-1 infection, which implicates P-k as a new endogenous cell-surface factor that may provide protection against HIV-1 infection. (Blood. 2009;113:4980-4991)
|
|
