| 1. |
- Adam, A, et al.
(författare)
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Abstracts from Hydrocephalus 2016.
- 2017
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Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Visvanathan, Kala, et al.
(författare)
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Circulating vitamin D and breast cancer risk : an international pooling project of 17 cohorts
- 2023
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Ingår i: European Journal of Epidemiology. - : Springer Science+Business Media B.V.. - 0393-2990 .- 1573-7284. ; 38, s. 11-29
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Tidskriftsartikel (refereegranskat)abstract
- Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42–68) years at blood collection and 63 (49–75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, calibrated to this assay to permit using a common metric. Study-specific relative risks (RRs) for season-standardized 25(OH)D concentrations were estimated by conditional logistic regression and combined by random-effects models. Circulating 25(OH)D increased from a median of 22.6 nmol/L in consortium-wide decile 1 to 93.2 nmol/L in decile 10. Breast cancer risk in each decile was not statistically significantly different from risk in decile 5 in models adjusted for breast cancer risk factors, and no trend was apparent (P-trend = 0.64). Compared to women with sufficient 25(OH)D based on Institute of Medicine guidelines (50– < 62.5 nmol/L), RRs were not statistically significantly different at either low concentrations (< 20 nmol/L, 3% of controls) or high concentrations (100– < 125 nmol/L, 3% of controls; ≥ 125 nmol/L, 0.7% of controls). RR per 25 nmol/L increase in 25(OH)D was 0.99 [95% confidence intervaI (CI) 0.95–1.03]. Associations remained null across subgroups, including those defined by body mass index, physical activity, latitude, and season of blood collection. Although none of the associations by tumor characteristics reached statistical significance, suggestive inverse associations were seen for distant and triple negative tumors. Circulating 25(OH)D, comparably measured in 17 international cohorts and season-standardized, was not related to subsequent incidence of invasive breast cancer over a broad range in vitamin D status.
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| 11. |
- Baron, F, et al.
(författare)
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Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation
- 2012
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Ingår i: Leukemia. - : Nature Publishing Group. - 0887-6924 .- 1476-5551. ; 26:12, s. 2462-2468
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Tidskriftsartikel (refereegranskat)abstract
- This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of relapse (hazards ratio (HR) 0.7, P = 0.02) translating into a trend for better overall survival (OS; HR 1.3; P = 0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR 0.4, P andlt; 0.0.001) owing to high risk of nonrelapse mortality (NRM; HR 5.2, P andlt; 0.0001). In time-dependent multivariate Cox analyses, limited chronic GVHD tended to be associated with a lower risk of relapse (HR 0.72; P = 0.07) translating into a better OS (HR 1.8; P andlt; 0.001), while extensive chronic GVHD was associated with a lower risk of relapse (HR 0.65; P = 0.02) but also with higher NRM (HR 3.5; P andlt; 0.001) and thus had no net impact on OS. In-vivo T-cell depletion with antithymocyte globulin (ATG) or alemtuzumab was successful at preventing extensive chronic GVHD (P andlt; 0.001), but without improving OS for ATG and even with worsening OS for alemtuzumab (HR 0.65; P = 0.001). These results highlight the role of the immune-mediated graft-versus-leukemia effect in the RIC allo-SCT setting, but also the need for improving the prevention and treatment of severe GVHD. Leukemia (2012) 26, 2462-2468; doi: 10.1038/leu.2012.135
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| 12. |
- Bonetti, Stefano, et al.
(författare)
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Direct observation and imaging of a spin-wave soliton with p−like symmetry
- 2015
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The prediction and realization of magnetic excitations driven by electrical currents via the spin transfer torque effect, enables novel magnetic nano-devices where spin-waves can be used to process and store information. The functional control of such devices relies on understanding the properties of non-linear spin-wave excitations. It has been demonstrated that spin waves can show both an itinerant character, but also appear as localized solitons. So far, it was assumed that localized solitons have essentially cylindrical, s−like symmetry. Using a newly developed high-sensitivity time-resolved magnetic x-ray microscopy, we instead observe the emergence of a novel localized soliton excitation with a nodal line, i.e. with p−like symmetry. Micromagnetic simulations identify the physical mechanism that controls the transition from s− to p−like solitons. Our results suggest a potential new pathway to design artificial atoms with tunable dynamical states using nanoscale magnetic devices.
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| 13. |
- Buckland, G., et al.
(författare)
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Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:10, s. 2504-2511
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Tidskriftsartikel (refereegranskat)abstract
- There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers. What's new? Urothelial cell carcinoma (UCC) is the most common form of bladder cancer. Previous studies suggested that plasma carotenoids, antioxidants found in fruit and vegetables, were associated with a decreased risk of UCC while a high intake of animal protein was associated with an increased cancer risk. Here, the authors conducted the first study to investigate the association between the Mediterranean diet, a diet rich in fresh fruits and vegetables and low in animal products, and UCC in Europe. They found that adherence to a Mediterranean diet was not significantly associated with UCC, regardless of level of tumour aggressiveness. They point out that these findings are in line with the rather weak evidence for questionnaire-based associations between dietary factors and bladder cancer risk.
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| 14. |
- Nagler, Arnon, et al.
(författare)
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Mobilized peripheral blood stem cells compared with bone marrow from HLA-identical siblings for reduced-intensity conditioning transplantation in acute myeloid leukemia in complete remission: a retrospective analysis from the Acute Leukemia Working Party of EBMT
- 2012
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Ingår i: European Journal of Haematology. - : John Wiley and Sons. - 0902-4441 .- 1600-0609. ; 89:3, s. 206-213
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Tidskriftsartikel (refereegranskat)abstract
- Reduced-intensity conditioning (RIC)-alloSCT is increasingly used for acute myelogenous leukemia. Limited data are available for the comparison of peripheral blood stem cells with bone marrow for RIC-alloSCT. We used the European Group for Blood and Marrow Transplantation (EBMT) ALWP data to compare the outcome of mobilized peripheral blood stem cells (PBSC) (n = 1430) vs. bone marrow (BM) (n = 107) for acute myelogenous leukemia (AML) patients with complete remission that underwent RIC-alloSCT from compatible sibling donors. The leukemia features, the disease status, and the time from diagnosis were similar between the two groups. Engraftment was achieved in 99% and 93% in the PBSC and BM groups, respectively (P andlt; 0.0001). The day of engraftment was significantly earlier for the PBSC vs. the BM group, 15 (159) and 19 (569), respectively (P andlt; 0.001). Acute GVHD, severe GVHD (grade IIIIV) and chronic GVHD did not differ between the groups. leukemia-free survival (LFS), relapse, and non-relapsed mortality (NRM) were 51 +/- 2%, 32 +/- 1%, and 17 +/- 1% vs. 50 +/- 6%, 38 +/- 6%, and 12 +/- 3% for the PBSC and BM groups, respectively. Our results indicate faster engraftment, but no difference in GVHD, LFS, relapse, and NRM when comparing PBSC to BM grafts from sibling donors following RIC conditioning. This is the first study comparing PBSC to BM grafts in the RIC setting, analyzing a homogeneous population of patients with AML in remission. Whether PBSC should be preferred for advanced phases of the disease, where the outcome is dominated by relapse incidences, needs further investigation.
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| 15. |
- Tsilidis, Konstantinos K., et al.
(författare)
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Diabetes mellitus and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:2, s. 372-381
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Tidskriftsartikel (refereegranskat)abstract
- The current epidemiologic evidence suggests that men with type 2 diabetes mellitus may be at lower risk of developing prostate cancer, but little is known about its association with stage and grade of the disease. The association between self-reported diabetes mellitus at recruitment and risk of prostate cancer was examined in the European Prospective Investigation into Cancer and Nutrition (EPIC). Among 139,131 eligible men, 4,531 were diagnosed with prostate cancer over an average follow-up of 12 years. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models stratified by EPIC-participating center and age at recruitment, and adjusted for education, smoking status, body mass index, waist circumference, and physical activity. In a subset of men without prostate cancer, the cross-sectional association between circulating concentrations of androgens and insulin-like growth factor proteins with diabetes status was also investigated using linear regression models. Compared to men with no diabetes, men with diabetes had a 26% lower risk of prostate cancer (HR, 0.74; 95% CI, 0.63-0.86). There was no evidence that the association differed by stage (p-heterogeneity, 0.19) or grade (p-heterogeneity, 0.48) of the disease, although the numbers were small in some disease subgroups. In a subset of 626 men with hormone measurements, circulating concentrations of androstenedione, total testosterone and insulin-like growth factor binding protein-three were lower in men with diabetes compared to men without diabetes. This large European study has confirmed an inverse association between self-reported diabetes mellitus and subsequent risk of prostate cancer. What's new? Emerging evidence suggests that men with type 2 diabetes are at lower risk to develop prostate cancer. Using data obtained within the European Prospective Investigation into Cancer and Nutrition (EPIC), the authors show that the prostate cancer risk was, indeed, reduced by 26% in men with type 2 diabetes but no association with cancer stage or grade was observed. In a subset of men for whom data on circulating hormones were available, levels of androstenedione, total testosterone and insulin-like growth factor binding protein-three were lower in those with diabetes as compared to those without diabetes, giving clues to how having diabetes could affect prostate cancer development.
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| 18. |
- Fedirko, V., et al.
(författare)
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Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: A nested case-control study
- 2014
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 60:4, s. 1222-1230
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Tidskriftsartikel (refereegranskat)abstract
- The association between vitamin D status and hepatocellular carcinoma (HCC) has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between prediagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and the risk of HCC in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n=138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRRs) of HCC associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of prediagnostic 25(OH)D were calculated using conditional logistic regression. Higher 25(OH)D levels were associated with a 49% reduction in the risk of HCC (highest versus lowest tertile: multivariable IRR=0.51, 95% confidence interval [CI], 0.26 to 0.99; Ptrend=0.04; per 10 nmol/L increase: IRR=0.80, 95% CI, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of preexisting liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. Conclusion: In this prospective study on western European populations, serum levels of 25(OH)D were inversely associated with the risk of HCC. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required. © 2014 by the American Association for the Study of Liver Diseases.
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| 19. |
- Malm-Erjefält, M., et al.
(författare)
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Circulating eosinophils in asthma, allergic rhinitis, and atopic dermatitis lack morphological signs of degranulation
- 2005
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Ingår i: Clin Exp Allergy. ; 35:10
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Tidskriftsartikel (refereegranskat)abstract
- Summary Background In allergic diseases, eosinophils in affected tissues release granule proteins with cytotoxic, immunoregulatory, and remodelling-promoting properties. From recent observations, it may be assumed that eosinophils degranulate already in circulating blood. If degranulation occurs in the circulation, this could contribute to widespread systemic effects and provide an important marker of disease. Objective To determine the degranulation status of circulating eosinophils in common allergic diseases. Methods Using a novel approach of whole blood fixation and leucocyte preparation, the granule morphology of blood eosinophils from healthy subjects, non-symptomatic patients, symptomatic patients with asthma, asthma and Churg-Strauss syndrome, allergic rhinitis, and atopic dermatitis was evaluated by transmission electron microscopy (TEM) and eosinophil peroxidase (TEM) histochemistry. Plasma and serum levels of eosinophil cationic protein were measured by fluoroenzymeimmunoassay. Selected tissue biopsies were examined by TEM. Results Regardless of symptoms, circulating eosinophils from allergic patients showed the same granule morphology as cells from healthy subjects. The majority of eosinophil-specific granules had preserved intact electron-density (96%; range: 89-98%), while the remaining granules typically exhibited marginal coarsening or mild lucency of the matrix structure. Abnormalities of the crystalline granule core were rarely detected. Furthermore, granule matrix alterations were not associated with any re-localization of intracellular EPO or increase in plasma eosinophil cationic protein. By contrast, eosinophils in diseased tissues exhibited cytolysis (granule release through membrane rupture) and piecemeal degranulation (loss of granule matrix and core structures). Conclusion In symptomatic eosinophilic diseases, circulating blood eosinophils retain their granule contents until they have reached their target organ.
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| 20. |
- Malm, Johan, et al.
(författare)
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Long-term prediction of prostate cancer diagnosis and death using PSA and obesity related anthropometrics at early middle age: Data from the malmö preventive project
- 2018
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:5, s. 5778-5785
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate whether anthropometric parameters add to PSA measurements in middle-aged men for risk assessment of prostate cancer (PCa) diagnosis and death. Results: After adjusting for PSA, both BMI and weight were significantly associated with an increased risk of PCa death with the odds of a death corresponding to a 10 kg/m2 or 10 kg increase being 1.58 (95% CI 1.10, 2.28; p = 0.013) and 1.14 (95% CI 1.02, 1.26; p = 0.016) times greater, respectively. AUCs did not meaningfully increase with the addition of weight or BMI to prediction models including PSA. Materials and Methods: In 1974 to 1986, 22,444 Swedish men aged 44 to 50 enrolled in Malmö Preventive Project, Sweden, and provided blood samples and anthropometric data. Rates of PSA screening in the cohort were very low. Documentation of PCa diagnosis and disease-specific death up to 2014 was retrieved through national registries. Among men with anthropometric measurements available at baseline, a total of 1692 men diagnosed with PCa were matched to 4190 controls, and 464 men who died of disease were matched to 1390 controls. Multivariable conditional logistic regression was used to determine whether diagnosis or death from PCa were associated with weight and body mass index (BMI) at adulthood after adjusting for PSA. Conclusions: Men with higher BMI and weight at early middle age have an increased risk of PCa diagnosis and death after adjusting for PSA. However, in a multivariable numerical statistical model, BMI and weight do not importantly improve the predictive accuracy of PSA. Risk-stratification of screening should be based on PSA without reference to anthropometrics. © Assel et al.
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| 25. |
- Villa, Luisa L., et al.
(författare)
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Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18
- 2006
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 24:27-28, s. 5571-5583
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus (HPV) infection causes cervical cancer and genital warts. Young women (1106) were randomized to receive one of three formulations of a quadrivalent HPV (Types 6/11/16/18) L1 virus-like particle (VLP) vaccine or one of two placebo formulations. The goal was to assess vaccine safety and immunogenicity in baseline HPV 6/11/16 or 18-naive and previously infected subjects. All three formulations were highly immunogenic. At Month 2 (postdose 1), among women with vaccine-type antibodies at baseline, vaccine-induced anti-HPV responses were similar to 12- to 26-fold higher than those observed in baseline-naive women, suggesting an anamnestic response. Following an initial, similar sized decline, anti-HPV responses plateaued and remained stable through end-of-study (3.0 years). No vaccine-related serious adverse experiences were reported. (c) 2006 Elsevier Ltd. All rights reserved.
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| 26. |
- Wang, Q., et al.
(författare)
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Wide-aperture GaAs/AlGaAs multiple quantum well electro-optic modulators
- 2002
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Ingår i: Proceedings of SPIE, the International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 4947, s. 59-67
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We present design and fabrication methods for surface normal monolithic amplitude modulators with an aperture up to 14 × 14 mm2, a contrast ratio of 6:1 and for low driving voltages (=8 V). The modulators consist of undoped GaAs/AlGaAs quantum wells embedded in a Fabry-Perot (FP) resonance cavity grown by MOVPE. To improve the device performance the FP cavity, the period and thickness of the quantum well and doping concentration were optimised. Also, the dimension of the modulator were varied from 0.5 × 0.5 to 14 × 14 mm2. The results show that the yield of the modulators increases significantly when decreasing the size of the modulators. To remedy the low yield issue for wide aperture modulator, a pixelated approach was used to divide the mono pixel in a monolithic modulator into several pixels, for example from 4 to 48. The modulation speed of the modulators with different dimensions was characterised by electro-optic (EO) response measurements. The temporal optical response of the large modulators was satisfactory up to the order of MHz modulation frequency where the RC constant limited the performance. A few of the modulators with wide apertures are to be assembled into an optical link system for free-space communication.
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| 30. |
- Cadenas, J., et al.
(författare)
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Regulation of human oocyte maturation in vivo during the final maturation of follicles
- 2023
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 38:4, s. 686-700
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Which substances and signal transduction pathways are potentially active downstream to the effect of FSH and LH in the regulation of human oocyte maturation in vivo? SUMMARY ANSWER: The regulation of human oocyte maturation appears to be a multifactorial process in which several different signal transduction pathways are active. WHAT IS KNOWN ALREADY: Many studies in animal species have provided insight into the mechanisms that govern the final maturation of oocytes. Currently, these studies have identified several different mechanisms downstream to the effects of FSH and LH. Some of the identified mechanisms include the regulation of cAMP/cGMP levels in oocytes involving C-type natriuretic peptide (CNP), effects of epidermal growth factor (EGF)-related peptides such as amphiregulin (AREG) and/or epiregulin (EREG), effect of TGF-β family members including growth differentiation factor 9 (GDF9) and morphogenetic protein 15 (BMP15), activins/inhibins, follicular fluid meiosis activating sterol (FF-MAS), the growth factor midkine (MDK), and several others. However, to what extent these pathways and mechanisms are active in humans in vivo is unknown. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 50 women undergoing fertility treatment in a standard antagonist protocol at a university hospital affiliated fertility clinic in 2016-2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: We evaluated the substances and signalling pathways potentially affecting human oocyte maturation in follicular fluid (FF) and granulosa cells (GCs) collected at five time points during the final maturation of follicles. Using ELISA measurement and proteomic profiling of FF and whole genome gene expression in GC, the following substances and their signal transduction pathways were collectively evaluated: CNP, the EGF family, inhibin-A, inhibin-B, activins, FF-MAS, MDK, GDF9, and BMP15. MAIN RESULTS AND THE ROLE OF CHANCE: All the evaluated substances and signal transduction pathways are potentially active in the regulation of human oocyte maturation in vivo except for GDF9/BMP15 signalling. In particular, AREG, inhibins, and MDK were significantly upregulated during the first 12-17 h after initiating the final maturation of follicles and were measured at significantly higher concentrations than previously reported. Additionally, the genes regulating FF-MAS synthesis and metabolism were significantly controlled in favour of accumulation during the first 12-17 h. In contrast, concentrations of CNP were low and did not change during the process of final maturation of follicles, and concentrations of GDF9 and BMP15 were much lower than reported in small antral follicles, suggesting a less pronounced influence from these substances. LARGE SCALE DATA: None. LIMITATIONS, REASONS FOR CAUTION: Although GC and cumulus cells have many similar features, it is a limitation of the current study that information for the corresponding cumulus cells is not available. However, we seldom recovered a cumulus-oocyte complex during the follicle aspiration from 0 to 32 h. WIDER IMPLICATIONS OF THE FINDINGS: Delineating the mechanisms governing the regulation of human oocyte maturation in vivo advances the possibility of developing a platform for IVM that, as for most other mammalian species, results in healthy offspring with good efficacy. Mimicking the intrafollicular conditions during oocyte maturation in vivo in small culture droplets during IVM may enhance oocyte nuclear and cytoplasmic maturation. The primary outlook for such a method is, in the context of fertility preservation, to augment the chances of achieving biological children after a cancer treatment by subjecting oocytes from small antral follicles to IVM. Provided that aspiration of oocytes from small antral follicles in vivo can be developed with good efficacy, IVM may be applied to infertile patients on a larger scale and can provide a cheap alternative to conventional IVF treatment with ovarian stimulation. Successful IVM has the potential to change current established techniques for infertility treatment. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the University Hospital of Copenhagen, Rigshospitalet, the Independent Research Fund Denmark (grant number 0134-00448), and the Interregional EU-sponsored ReproUnion network. There are no conflicts of interest to be declared.
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| 32. |
- Ezzat, Kariem, et al.
(författare)
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The viral protein corona directs viral pathogenesis and amyloid aggregation
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Artificial nanoparticles accumulate a protein corona layer in biological fluids, which significantly influences their bioactivity. As nanosized obligate intracellular parasites, viruses share many biophysical properties with artificial nanoparticles in extracellular environments and here we show that respiratory syncytial virus (RSV) and herpes simplex virus type 1 (HSV-1) accumulate a rich and distinctive protein corona in different biological fluids. Moreover, we show that corona pre-coating differentially affects viral infectivity and immune cell activation. In addition, we demonstrate that viruses bind amyloidogenic peptides in their corona and catalyze amyloid formation via surface-assisted heterogeneous nucleation. Importantly, we show that HSV-1 catalyzes the aggregation of the amyloid beta-peptide (A beta(42)), a major constituent of amyloid plaques in Alzheimer's disease, in vitro and in animal models. Our results highlight the viral protein corona as an acquired structural layer that is critical for viral-host interactions and illustrate a mechanistic convergence between viral and amyloid pathologies.
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| 34. |
- Grahn, J. V., et al.
(författare)
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A low-complexity 62-GHz f(T) SiGe heterojunction bipolar transistor process using differential epitaxy and in situ phosphorus-doped poly-Si emitter at very low thermal budget
- 2000
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Ingår i: Solid-State Electronics. - 0038-1101 .- 1879-2405. ; 44:3, s. 549-554
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Tidskriftsartikel (refereegranskat)abstract
- A low-complexity SiGe heterojunction bipolar transistor process based on differential epitaxy and in situ phosphorus doped polysilicon emitter technology is described. Silane-based chemical vapor deposition at reduced pressure was used for low-temperature SiGe epitaxy. Following SiGe epitaxy, the process temperature budget was kept very low with 900 degrees C for 10 s as the highest temperature step. A very high current gain of almost 2000 and cut off frequency of 62 GHz were achieved for a uniform 12% Ge profile. The breakdown voltage BVCEO and forward Early voltage were equal to 2.9 and 6.5 V, respectively.
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| 39. |
- Jansson, U, et al.
(författare)
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Low temperature epitaxial growth of metal carbides using fullerenes
- 2001
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Ingår i: Surface & Coatings Technology. - 0257-8972 .- 1879-3347. ; 142-144, s. 817-822
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Tidskriftsartikel (refereegranskat)abstract
- Epitaxial transition metal carbides can be deposited at low temperatures by simultaneous evaporation of C60 and either metal e-beam evaporation or metal d.c. magnetron sputtering. Hitherto, epitaxial films of TiC, VC, NbC, MoC, W2C and WC have been deposited on MgO(100), MgO(111) and in some cases 6H- and 4H-SiC(0001). Epitaxial TiC films with a good quality have been deposited at temperatures as low as 100°C with metal sputtering, while somewhat higher temperatures (> 200°C) are required for the other metals. In general, the plasma-assisted process allows lower deposition temperatures than the co-evaporation process. Most carbides can be deposited in a wide range of compositions within their homogeneity ranges by a fine-tuning of the Me/C60 flux. However, the results suggest that the formation of free surface carbon can be a limiting factor. The processes have also been used to deposit superlattices of TiC/NbC and TiC/VC at 400-500°C as well as epitaxial ternary Tix V1-xCy films. Furthermore, epitaxial films of ternary carbides with well-controlled metal concentration profiles can be deposited at temperatures below 500°C. © 2001 Elsevier Science B.V. All rights reserved.
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| 40. |
- Jantti, H, et al.
(författare)
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Human PSEN1 Mutant Glia Improve Spatial Learning and Memory in Aged Mice
- 2022
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:24
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Tidskriftsartikel (refereegranskat)abstract
- The PSEN1 ΔE9 mutation causes a familial form of Alzheimer’s disease (AD) by shifting the processing of amyloid precursor protein (APP) towards the generation of highly amyloidogenic Aβ42 peptide. We have previously shown that the PSEN1 ΔE9 mutation in human-induced pluripotent stem cell (iPSC)-derived astrocytes increases Aβ42 production and impairs cellular responses. Here, we injected PSEN1 ΔE9 mutant astrosphere-derived glial progenitors into newborn mice and investigated mouse behavior at the ages of 8, 12, and 16 months. While we did not find significant behavioral changes in younger mice, spatial learning and memory were paradoxically improved in 16-month-old PSEN1 ΔE9 glia-transplanted male mice as compared to age-matched isogenic control-transplanted animals. Memory improvement was associated with lower levels of soluble, but not insoluble, human Aβ42 in the mouse brain. We also found a decreased engraftment of PSEN1 ΔE9 mutant cells in the cingulate cortex and significant transcriptional changes in both human and mouse genes in the hippocampus, including the extracellular matrix-related genes. Overall, the presence of PSEN1 ΔE9 mutant glia exerted a more beneficial effect on aged mouse brain than the isogenic control human cells likely as a combination of several factors.
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| 41. |
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| 42. |
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| 43. |
- Kristensen, B, et al.
(författare)
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Hyperhomocysteinemia and hypofibrinolysis in young adults with ischemic stroke.
- 1999
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 30:5, s. 974-80
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Data from epidemiological and case-control studies suggest that increased total homocysteine (tHcy) levels are associated with increased risk for thromboembolic disease. The mechanisms by which hyperhomocysteinemia contributes to thrombogenesis are incompletely understood. The main objectives of this study of young ischemic stroke patients were (1) to examine fasting and post-methionine load levels of tHcy, (2) to ascertain the genotype frequency of the C677CT mutation in the methylenetetrahydrofolate reductase gene (TT genotype), and (3) to study the possible interaction between plasma tHcy levels and fibrinolytic factors.METHODS: This case-control study was based on 80 consecutive patients aged 18 to 44 years admitted between January 1992 and May 1996 as a result of a first-ever ischemic stroke. Forty-one healthy control subjects were recruited. Measurement of fasting tHcy and post-methionine load levels and evaluation of the fibrinolytic system were undertaken at least 3 months (mean, 5.1+/-1. 9 months) after admission. Genotyping of the methylenetetrahydrofolate reductase gene was performed.RESULTS: Although the increase after methionine loading (ie, postload tHcy minus fasting-level tHcy) was significantly higher among patients, there was no difference in fasting and postload tHcy levels. After adjustment for conventional risk factors, elevated postload increase tHcy levels were associated with a 4.8-fold increased risk of ischemic stroke. There was no difference between patients and control subjects in either TT genotype frequency or T allele frequency. Abnormal response to methionine loading was associated with higher tissue plasminogen activator (tPA) mass concentration, higher plasminogen activator inhibitor-1 levels, and lower tPA activity. After adjustment for age, sex, body mass index, serum cholesterol, and triglycerides, an abnormal increase in postload tHcy levels remained significantly associated with tPA mass concentration levels (P=0.03).CONCLUSIONS: A moderately elevated increase in tHcy levels after methionine loading was associated with an increased risk for ischemic stroke in young adults. In contrast, fasting tHcy levels did not differ between patients and controls. A moderately elevated increase in tHcy after methionine loading may provide a additional thrombogenic risk mediated in part by interactions with the fibrinolytic system. In young stroke patients, a methionine loading test to detect hyperhomocysteinemia should always be considered in the convalescent phase of the disease.
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| 44. |
- Kristensen, B, et al.
(författare)
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Increased fibrinogen levels and acquired hypofibrinolysis in young adults with ischemic stroke.
- 1998
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 29:11, s. 2261-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Elevated fibrinogen levels and abnormalities in the fibrinolytic system are related to the occurrence of cardiovascular events. However, the role of these factors in the evolution of cerebrovascular disease has received less attention, in particular in young stroke patients. The aim of this study was to evaluate possible abnormalities in plasma fibrinogen levels and the state of the fibrinolytic system in young adults with a first-ever ischemic stroke.METHODS: This study is based on 102 consecutive patients aged 18 to 44 years admitted between January 1991 and May 1996 as a result of a first ischemic stroke. Forty-one healthy controls were recruited. Evaluations of anthropometric/metabolic variables, plasma fibrinogen levels, and the fibrinolytic system were undertaken >/=3 months (mean, 5.4+/-2.0 months) after admission.RESULTS: Patients had lower tissue plasminogen activator activity and increased plasminogen activator inhibitor type 1 activity at baseline, as well as increased tissue plasminogen activator mass concentration both at baseline and after a venous occlusion test. Overall, there were no significant differences between the main etiologic subgroups regarding plasma fibrinogen levels and fibrinolytic variables. Baseline fibrinolytic variables were strongly correlated with body mass index, serum triglycerides, and cholesterol levels. After adjustments in multivariate models, fibrinogen levels and tissue plasminogen activator mass concentration both at baseline and after venous occlusion test remained significantly increased in patients. Logistic multiple regression analyses indicated that plasma fibrinogen was a strong predictor of ischemic stroke (odds ratio, 11.25; 95% CI, 3.27 to 38. 69).CONCLUSIONS: Increased fibrinogen levels and tissue plasminogen activator mass concentration are independently associated with ischemic stroke in young adults. Metabolic perturbations are closely interrelated with aberrations in tissue plasminogen activator and plasminogen activator inhibitor type 1 activity in these patients, findings consistent with an acquired hypofibrinolysis.
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| 45. |
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| 46. |
- Luczynska, Anna, et al.
(författare)
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Plasma 25-hydroxyvitamin D concentration and lymphoma risk: results of the European Prospective Investigation into Cancer and Nutrition
- 2013
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Ingår i: American Journal of Clinical Nutrition. - Rockville Pike, Bethesda, MD, USA : Elsevier BV. - 1938-3207 .- 0002-9165. ; 98:3, s. 827-838
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relation between vitamin D status and lymphoma risk is inconclusive. Objective: We examined the association between prediagnostic plasma 25-hydroxyvitamin D [25(OH)D] and lymphoid cancer risk. Design: We conducted a study nested within the European Prospective Investigation into Cancer and Nutrition cohort of 1127 lymphoma cases and 1127 matched controls with a mean follow-up time of 7.1 y. Conditional logistic regression was used to estimate multivariable-adjusted incidence rate ratios of lymphoma risk in relation to plasma 25(OH)D. Season-standardized and season-specific 25(OH)D quartiles were used. We also analyzed 25(OH)D as a continuous variable and used predefined cutoffs. Results: No statistically significant association between plasma 25(OH)D and overall lymphoid cancer risk was observed. A positive association for B-cell non-Hodgkin lymphoma was noted only in those with a diagnosis made during the first 2 y of follow-up (P-heterogeneity = 0.03), which suggests the possibility of reverse causality. Further analysis restricted to participants with >= 2y of follow-up time showed a significant association between 25(OH)D and chronic lymphocytic leukemia (CLL) (n = 161): adjusted incidence rate ratios were 0.40 (95% CI: 0.18, 0.90; P-trend = 0.05) and 0.31 (95% CI: 0.13, 0.76; P-trend = 0.03) for the top compared with the bottom season-standardized and season-specific quartiles, respectively. Data on dietary vitamin D intake provided further support for the observed association (incidence rate ratio: 0.33; 95% CI = 0.12, 0.89; P-trend = 0.006). Conclusions: Our findings do not support a protective role of high 25(OH)D concentration in lymphoid cancers overall. However, they suggest that higher concentrations of 25(OH)D are associated with a reduced risk of CLL.
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| 47. |
- Lundwall, Åke, et al.
(författare)
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Chemical characterization of the predominant proteins secreted by mouse seminal vesicles
- 1997
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Ingår i: Eur J Biochem. ; 249:1, s. 39-44
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Tidskriftsartikel (refereegranskat)abstract
- Mouse seminal vesicles secrete four major protein components with estimated molecular masses of 95, 38, 17, and 16 kDa. Amino acid sequencing revealed that the 95-kDa component represents a protein with an unknown structure, while the 38-kDa component was identified as semenoclotin, the 17-kDa component as seminal-vesicle-secreted protein IV, and the 16-kDa component as seminal-vesicle-secreted protein V. Semenoclotin and the 95-kDa component were readily cross-linked by transglutaminase, suggesting that the two proteins are involved in the formation of the mouse copulatory plug. Treatment of mouse seminal vesicle fluid with human prostate-specific antigen rapidly degraded semenoclotin, indicating a structural resemblance of this protein to human semenogelins, despite the vast difference in primary structure. As previously reported for other seminal-vesicle-secreted proteins, the semenoclotin transcripts are shown to be under androgen control.
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| 48. |
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| 49. |
- Malm, Gunilla, et al.
(författare)
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Reproductive function during summer and winter in Norwegian men living north and south of the Arctic circle.
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 89:9, s. 4397-4402
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Tidskriftsartikel (refereegranskat)abstract
- Seasonal, daylight-dependent variation in human spermatozoa counts, with lowest values during summer, has been suggested. To test this hypothesis, we performed a longitudinal study of semen quality and reproductive hormone levels in Norwegian men living north and south of the Arctic Circle. An ejaculate and a serum specimen were obtained both in summer and in winter from 92 volunteers in Tromsoe (69° north latitude) and 112 in Oslo (60° north latitude). Semen analyses were performed, and serum was assayed for FSH and inhibin B. The median spermatozoa concentration in Tromsoe after adjustment for abstinence period length was 49 × 106/ml in summer and 54 × 106/ml in winter. Corresponding values for Oslo were 59 × 106/ml and 54 × 106/ml. The seasonal differences in spermatozoa concentration were not statistically significant, nor were significant differences observed in median total spermatozoa count, semen volume, percentage progressive motile spermatozoa, or FSH. In Tromsoe, but not Oslo, inhibin B concentration was slightly, but significantly (P = 0.02) higher in winter than summer (229 ng/liter vs. 223 ng/liter).The length of the daylight period may have a slight impact on hormonal markers of spermatogenesis but does not cause substantial changes in spermatozoa numbers and motility.
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| 50. |
- Malm, J, et al.
(författare)
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CSF monoamine metabolites, cholinesterases and lactate in the adult hydrocephalus syndrome (normal pressure hydrocephalus) related to CSF hydrodynamic parameters.
- 1991
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - 0022-3050 .- 1468-330X. ; 54:3, s. 252-9
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Tidskriftsartikel (refereegranskat)abstract
- Monoamine metabolites, cholinesterases and lactic acid in lumbar cerebrospinal fluid (CSF) were investigated on patients with the adult hydrocephalus syndrome (idiopathic normal pressure syndrome; AHS, n = 15), Alzheimer's disease (AD, n = 14), multi-infarct dementia (MID, n = 13) and controls (n = 21). Patients had clinical and CSF hydrodynamic investigations. Monoamine concentrations were determined by reversed-phase liquid chromatography, cholinesterases and lactate were determined photometrically. In the AHS patients, CSF monoamine concentrations were not significantly different compared with controls, AD or MID patients. AHS and AD patients showed a similar reduction of CSF acetylcholinesterase activity compared with controls. Positive correlations were found in concentrations of CSF homovanillic acid, CSF 5-hydroxyindoleacetic acid and CSF lactic acid versus CSF outflow conductance (that is, resistance against CSF outflow) in the AHS patients. A similar pattern was observed in a subgroup of MID patients characterised by dilated ventricles and disturbed CSF hydrodynamics. These data suggest that a low CSF outflow conductance may facilitate the clearance of acidic substances from the arachnoid space at the probenecid sensitive active transport site. Alternative explanations would be that a pathologically low CSF outflow conductance is accompanied by an inverse caudorostral flow of CSF or a compromised trans-ependymal diffusion.
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