| 132081. |
- Nyström, Jenny, 1972, et al.
(author)
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CRIM1 is localized to the podocyte filtration slit diaphragm of the adult human kidney
- 2009
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In: Nephrol Dial Transplant. - : Oxford University Press (OUP). - 1460-2385 .- 1460-2385 .- 0931-0509. ; 24:7, s. 2038-44
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Journal article (peer-reviewed)abstract
- BACKGROUND: CRIM1 is a plasma membrane bound protein containing six cysteine-rich repeats (CRR). Through these, CRIM1 has been shown to interact with a subgroup of the TGF-beta superfamily, the bone morphogenic proteins (BMP) isoforms 2, 4 and 7. The probable action is to modulate the signalling properties of these factors. CRIM1 has also been shown to regulate the release of VEGFA by podocytes during renal organogenesis. Knock-out studies in mice have shown that CRIM1 is critically involved in the development of the central nervous system, eye and kidney. Replacement of CRIM1 with a defective version leads to renal dysgenesis and perinatal death. We have analysed the distribution of CRIM1 in adult human renal tissue. METHODS: To this end, we have used immunofluorescence, immunohistochemistry and immunoelectron microscopy. We performed western blotting for the CRIM1 protein, using lysates from isolated glomerular podocytes and human renal tissue homogenate. By using quantitative PCR, we compared the CRIM1 mRNA levels in podocytes, human renal tissue homogenate, primary human renal proximal tubular epithelial cells and primary human pulmonary artery smooth muscle cells. RESULTS: The results show that in the human adult kidney, CRIM1 is mainly expressed in the glomerular podocytes and is associated with the insertional region of the filtration slit diaphragm (SD) of the podocyte pedicles. CONCLUSIONS: CRIM1 is a protein that should be added to the list of proteins associated with the podocyte filtration SD and with the probable action of modulating BMP and VEGFA signalling.
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| 132082. |
- Nyström, Jessica
(author)
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Functional role of T-cell activation in viral hepatitis
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Hepatitis B and C (HBV, HCV) constitute global health problems and there are approximately 350 million chronically HBV infected people around the world, most of them are found in East and South East Asia and Africa. Worldwide there are 170 million HCV infected individuals with the highest prevalence seen in Egypt. Reported cases of HBV and HCV have decreased significantly due to improvements in screening of blood donors and in particular with respect to HBV due to the introduction of a preventive vaccine. HBV and HCV are transmitted mainly by blood-to-blood contact or by sexual transmission (less efficient for HCV). There are great differences in the ability to clear the viral infection between HBV and HCV infected individuals. In HCV almost 75% develop a chronic disease, while the rate of chronicity caused by HBV is influenced by the age at infection. Thus, only 5% of adult-acquired infection leads to chronic hepatitis B (CHB) whereas the chronicity rate for perinatal infection is up to 90%. Failure to mount effective T cell responses may possibly cause both an inability to respond to HBV vaccination, as well as to CHB. Protective immunity towards HBV can be achieved by vaccination; the protection is based on the emergence of antibodies to the hepatitis B surface antigen (anti-HBs). Though a small group of individuals i.e. non-responders (5 to 10%) fail to do this. We therefore designed a study where previously nonresponders to the HBV vaccine were re-vaccinated using a double dose of the combined hepatitis A virus (HAV) and HBV vaccine in hope to improve priming of a protective HBV response. Almost all non-responders developed protective levels of anti-HBs and approximately half of the patients developed a HBs antigen (HBsAg)-speific T-cell proliferation after re-vaccination. Thus, a nonresponse to the HBV vaccine is not absolute, it most often represent a low responder satus which can be circumvented with the appropriate stimulus. We next investigated how HBV-specific T-cell responses emerged in children with different stages of CHB. In the majority of children an HBV core antigen (HBcAg) specific T-cell proliferation was detected, also in an anti-HBeAg positive group, indicating that a continuous T-cell proliferation is important to maintain HBe antigen (HBeAg) clearance. Exogenous HBcAg is well known to be a potent activator of both B cells and T helper (TH). An intrinsic feature of HBcAg it is the binding to naïve human and mouse B-cells. Its high immunogenicity suggests that it may be a good target for immunotherapy. Essential for this binding were the residue 76 to 80 on the tip of the spike of the HBcAg.We could also note that the induced CD8+ T-cell response after immunization with endogenously expressed HBcAg was not Bcell dependent whereas priming with exogenously expressed HBcAg was. New treatment strategies are needed for both HBV and HCV infections. We have developed two DNA based vaccines, one based on HBcAg for HBV: and the other based on the non-structural protein 3/4A (NS3/4A) for HCV. Previous studies have shown that the HBcAg- and NS3/4A-vaccine induce both a strong humoral and cellular response in mice, but less is known if they are functional in the liver. We therefore developed a model to test if CD8+ T-cells could home to the liver and eliminate NS3/4A expressing hepatocytes. Transiently transgenic mice were generated using hydrodynamic injection of HBcAg- or NS3/4A-expressing plasmids. We could show that the primed peripheral CD8+ T cells indeed entered the liver and eliminated NS3/4A expressing hepatocytes. We lastly characterized the ability of HBcAg-DNA to induce CTLs. We found that HBcAg-DNA was surprisingly poor in inducing CTLs at a low DNA level when compared to the NS3/4A gene. Despite delivery by in vivo electroporation and gene codon optimization, low levels of DNA still failed to effectively prime CTLs. This is an unexpected property of HBcAg. Overall, these studies show that a poor T cell response, or poor ability to activate T cells, can effectively be overcomed by the appropriate measures, which has implications for human vaccine design.
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| 132083. |
- Nyström, Jessica, et al.
(author)
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Improved cell mediated immune responses after successful re-vaccination of non-responders to the hepatitis B virus surface antigen (HBsAg) vaccine using the combined hepatitis A and B vaccine
- 2008
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In: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 26:47, s. 5967-5972
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Journal article (peer-reviewed)abstract
- We Successfully re-vaccinated hepatitis B Virus (HBV) vaccine non-responders Using a double dose of the combined hepatitis A virus (HAV) and HBV vaccine. The hope was to improve priming of hepatitis B surface antigen (HBsAg)-specific cell mediated immune response (CMI) by an increased antigen dose and a theoretical adjuvant-effect from the local presence of a HAV-specific CMI. A few non-responders had a detectable HBsAg-specific CMI before re-vaccination. An in vitro detectable HBsAg-specific CMI was primed equally effective in non-responders (58%) as in first time vaccine recipients (68%). After the third dose a weak, albeit significant, association was observed between the magnitude of HBsAg-specific proliferation and anti-HBs levels. This regimen improves the priming of HBsAg-specific CMIs and antibodies.
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| 132084. |
- Nyström-Kandola, Jennifer, et al.
(author)
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Low concentrations of perfluoroalkyl acids (PFAAs) in municipal drinking water associated with serum PFAA concentrations in Swedish adolescents
- 2023
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In: Environment International. - 0160-4120 .- 1873-6750. ; 180
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Journal article (peer-reviewed)abstract
- While highly contaminated drinking water (DW) is a major source of exposure to perfluoroalkyl acids (PFAAs), the contribution of low-level contaminated DW (i.e. < 10 ng/L of individual PFAAs) to PFAA body burdens has rarely been studied. To address this knowledge gap, we evaluated the association between concentrations of perflurooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS) and perfluorooctane sulfonic acid (PFOS), and their sum (∑4PFAAs) in DW and serum in Swedish adolescents using weighted least squares regression. We paired serum PFAA concentrations in adolescents (age 10–21 years, n = 790) from the dietary survey Riksmaten Adolescents 2016–17 (RMA) with mean PFAA concentrations in water samples collected in 2018 from waterworks (n = 45) supplying DW to the participant residential and school addresses. The median concentrations of individual PFAAs in DW were < 1 ng/L. Median concentrations of PFNA and PFHxS in serum were < 1 ng/g, while those of PFOA and PFOS were 1–2 ng/g. Significant positive associations between PFAA concentrations in DW and serum were found for all four PFAAs and ∑4PFAAs, with estimated serum/DW concentration ratios ranging from 210 (PFOA) to 670 (PFHxS), taking exposure from sources other than DW (background) into consideration. The mean concentrations of PFHxS and ∑4PFAA in DW that would likely cause substantially elevated serum concentrations above background variation were estimated to 0.9 ng/L and 2.4 ng/L, respectively. The European Food Safety Authority has determined a health concern concentration of 6.9 ng ∑4PFAAs/mL serum. This level was to a large degree exceeded by RMA participants with DW ∑4PFAA concentrations above the maximum limits implemented in Denmark (2 ng ∑4PFAAs/L) and Sweden (4 ng ∑4PFAAs/L) than by RMA participants with DW concentrations below the maximum limits. In conclusion, PFAA exposure from low-level contaminated DW must be considered in risk assessment for adolescents.
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| 132085. |
- Nyström, Lennarth, et al.
(author)
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Long-term effects of mammography screening : Updated overview of the Swedish randomised trials
- 2002
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 359:9310, s. 909-919
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Journal article (peer-reviewed)abstract
- Background: There has been much debate about the value of screening mammography. Here we update the overview of the Swedish randomised controlled trials on mammography screening up to and including 1996. The Kopparberg part of the Two-County trial was not available for the overview, but the continuation of the Malm÷ trial (MMST II) has been added. The article also contains basic data from the trials that have not been presented before. Methods: The trials (n=247 010, invited group 129 750, control group 117 260) have been followed up by record linkage to the Swedish Cancer and Cause of Death Registers. The relative risks (RR) for breast cancer death and mortality were calculated for the invited and the control groups. The trial-specific as well as the age-specific effects were analysed. RRs were calculated by the density method, with total person-time experience of the cohort by time interval of follow-up as a basis for estimating mortality rates. We calculated weighted RRs and 95% CI with the Mantel-Haenszel procedure. Findings: The median trial time - the time from randomisation until the first round was completed for the control group or if the control group was not invited, until end of follow-up - was 6.5 years (range 3.0-18.1). The median follow-up time, the time from randomisation, to the end of follow-up, was 15.8 years (5.8-20.2). There were 511 breast cancer deaths in 1 864 770 women-years in the invited groups and 584 breast cancer deaths in 1 688 440 women-years in the control groups, a significant 21% reduction in breast cancer mortality (RR=0.79, 95% CI 0.70-0.89). The reduction was greatest in the age group 60-69 years at entry (33%). Looking at 5-year age groups, there were statistically significant effects in the age groups 55-59, 60-64, and 65-69 years (RR=0.76, 0.68, and 0.69, respectively). There was a small effect in women 50-54 years at randomisation (RR=0.95). The benefit in terms of cumulative breast cancer mortality started to emerge at about 4 years after randomisation and continued to increase to about 10 years. Thereafter the benefit in absolute terms was maintained throughout the period of observation. The age-adjusted relative risk for the total mortality was 0.98 (0.96-1.00). Interpretation: The advantageous effect of breast screening on breast cancer mortality persists after long-term follow-up. The recent criticism against the Swedish randomised controlled trials is misleading and scientifically unfounded.
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| 132086. |
- Nyström, Lennarth, 1944-, et al.
(author)
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Reduced breast cancer mortality after 20+years of follow-up in the Swedish randomized controlled mammography trials in Malmo, Stockholm, and Goteborg
- 2017
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In: Journal of Medical Screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 24:1, s. 34-42
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Journal article (peer-reviewed)abstract
- Objective: To analyze the age- and trial-specific effects of the breast cancer screening trials with mammography in Malmo , Stockholm, and Goteborg. Methods: The original trial files were linked to the Swedish Cancer and Cause of Death Registers to obtain date of breast cancer diagnosis and date and cause of death. Relative risks and 95% confidence intervals were calculated using the evaluation model (only breast cancers diagnosed between date of randomization and date when the first screening round of the control group was completed were included in the analysis). Results: Women aged 40-70 at randomization in the Malmo I and II, Stockholm, and Goteborg trials were followed-up for an average of 30, 22, 25, and 24 years, respectively. The overview of all trials resulted in a significant decrease of 15% in breast cancer mortality. The variation by consecutive 10-year age group at randomization was small-from 21% in the age group 40-49 to 11% in the age group 50-59. After adjustment for age, there was a significant reduction in breast cancer mortality in the Goteborg trial (26%), and a non-significant reduction in the Malmo I and II and Stockholm trials (12%, 15%, and 5.8%, respectively). Conclusions: The overview showed a 15% significant relative reduction in breast cancer mortality due to invitation to mammography screening. Heterogeneity in age, trial time, attendance rates, and length of screening intervals may have contributed to the variation in effect between the trials.
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| 132087. |
- Nyström, Markus B. T., et al.
(author)
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Behavioral activation versus physical activity via the internet : A randomized controlled trial
- 2017
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In: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 215, s. 85-93, s. 396-396
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Journal article (peer-reviewed)abstract
- Background: A major problem today is that only about fifty percent of those affected by depressionseeks help. One way to reach more sufferers would be by offering easily accessible internet based treatments. The purpose of this study was to compare/evaluate four therapist supported internet administered treatments.Method/results: Two hundred eighty six participants were included. The treatment period lasted twelve weeks, consisting of the following treatments: 1) physical activity without treatment rational, 2) physical activity with treatment rational, 3) behavioral activation without treatment rational and 4) behavioral activation with treatment rational. All groups (including a control-group) showed a significant decrease in depressive symptoms. When the treatment groups were pooled and compared to the control group, there were significant differences from pretest to posttest (Hedges gav treatment =1.01, control group =0.47). This held true also when each of the four treatment groups was compared to the control group, with one exception: Physical activity without treatment rationale.Limitations: The differences between how many modules the participants completed could indicate that there are other factors than the treatments that caused the symptom reduction, however, the dose-response analysis did not detect any significant differences on account of modules completed.Conclusions: The results support the positive effects of internet administered treatments for depression, and highlights the importance of psychoeducation, which tends to affect both the treatment outcome and the probability of remaining in treatment. These aspects need to be considered when developing and conducting new treatments for depression, since they would increase the likelihood of positive treatment outcomes.
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| 132088. |
- Nyström, Monica
(author)
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Characteristics of health care organizations associated with learning and development : lessons from a pilot study
- 2009
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In: Quality Management in Health Care. - Lippincott : Williams & Williams. - 1063-8628 .- 1550-5154. ; 18:4, s. 285-294
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Journal article (peer-reviewed)abstract
- Characteristics of health care organizationsassociated with an ability to learn from experiencesand to develop and manage change were exploredin this study. Understanding of these characteristicsis necessary to identify factors influencing successin learning from the past and achieving futurehealth care quality objectives. A literature review ofthe quality improvement, strategic organizationaldevelopment and change management,organizational learning, and microsystems fieldsidentified 20 organizational characteristics, groupedunder (a) organizational systems, (b) key actors, and(c) change management processes. Qualitativemethods, using interviews, focus group reports, andarchival records, were applied to find associationsbetween identified characteristics and 6 Swedishhealth care units externally evaluated as deliveringhigh-quality care. Strong support for a characteristicwas defined as units having more than 4 sourcesdescribing the characteristic as an importantsuccess factor. Eighteen characteristics had strongsupport from at least 2 units. The strongest evidencewas found for the following: (i) key actors havelong-term commitment, provide support, and makesense of ambiguous situations; (ii) organizationalsystems encourage employee commitment,participation, and involvement; and (iii) changemanagement processes are employedsystematically. Based on the results, a new model of“characteristics associated with learning anddevelopment in health care organizations” isproposed.
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| 132089. |
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| 132090. |
- Nyström, Monica E., et al.
(author)
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Advancing Health Services Collaborative and Partnership Research : Comment on "Experience of Health Leadership in Partnering with University-Based Researchers in Canada – A Call to 'Re-imagine' Research"
- 2021
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In: International Journal of Health Policy and Management. - : Kerman University of Medical Sciences. - 2322-5939. ; 10:2, s. 106-110
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Journal article (other academic/artistic)abstract
- Bowen et al highlight the trend towards partnership research to address the complex challenges currently facing healthcare systems and organizations world-wide. They focus on important strategic actors in partner organizations and their experiences, views and advice for sustainable collaboration, within a Canadian context. The authors call for a multi-system change to provide better conditions for research partnerships. They highlight needs to re-imagine research, to move beyond an ‘acute care’ and clinical focus in research, to re-think research funding, and to improve the academic preparation for research partnerships. In this commentary we provide input to the discussion on practical guidance for those involved in research partnerships based on our partnership experiences from ten research projects conducted within the Swedish healthcare system since 2007. We also highlight areas that need attention in future research in order to learn from approaches used for collaborative and partnership research.
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