| 1. |
- Gyllenberg, A, et al.
(author)
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Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
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In: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
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Journal article (peer-reviewed)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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| 2. |
- Sedimbi, S. K., et al.
(author)
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SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
- 2007
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In: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21
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Journal article (peer-reviewed)abstract
- SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
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| 3. |
- Landin-Olsson, Mona, et al.
(author)
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Immunoreactive trypsin(Ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls
- 1990
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In: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177. ; 5:3, s. 241-247
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Journal article (peer-reviewed)abstract
- To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive an-odal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) µg/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) µg/L in control subjects (p < 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) µg/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) µg/L in control subjects (p < 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p < 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.
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| 4. |
- Tai, F, et al.
(author)
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Abdominal Wall Miscellaneous
- 2015
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In: Hernia : the journal of hernias and abdominal wall surgery. - 1248-9204. ; 19 Suppl 1, s. S5-S12
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Journal article (peer-reviewed)
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| 5. |
- Lindehammer, Sabina, et al.
(author)
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Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk
- 2008
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In: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 45:4, s. 231-5
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Journal article (peer-reviewed)abstract
- The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
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| 6. |
- Sanjeevi, Carani B., et al.
(author)
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The risk conferred by HLA-DR and DQ for type 1 diabetes in 0-35-year age group are different in different regions of Sweden
- 2008
-
In: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. - 9781573317337 ; 1150, s. 106-11
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Journal article (peer-reviewed)abstract
- HLA DR4-DQ8 and DR3-DQ2 haplotypes account for 89% of newly diagnosed cases of type 1 diabetes (T1D) in Sweden. The presence of a single copy of DQ6 confers protection. The aim of the present study is to evaluate whether the risk conferred by high risk HLA DR and DQ to T1D is similar in all regions of Sweden and see whether there are any significant regional differences. The subjects comprised 799 consecutively diagnosed T1D patients and 585 age-, sex-, and geography-matched healthy controls in the age group 0-35 years. HLA typing for high-risk haplotypes was previously performed using PCR-SSOP and RFLP. The results showed that HLA DR3-DR4 gave an odds ratio of 8.14 for the whole of Sweden. However, when the study group was divided into six geographical regions, subjects from Stockholm had the highest OR, followed by those from Lund, Linköping, Gothenburg, Umeå, and Uppsala. Absolute protection was conferred by the presence of DQ6 in subjects from the Linköping region, but varied in the other regions. The frequency of DR3 and DQ2, DR4 and DQ8, DR15, and DQ6 in patients showed high linkage for each region, but were different between regions. In conclusion: The risk conferred by high-risk HLA varies in different regions for a homogenous population in Sweden. The results highlight the important role played by the various environmental factors in the precipitation of T1D.
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| 7. |
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| 8. |
- Norppa, H., et al.
(author)
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Chromosomal aberrations and SCEs as biomarkers of cancer risk
- 2006
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In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. - : Elsevier BV. - 1879-2871 .- 0027-5107. ; 600:1-2, s. 37-45
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Journal article (peer-reviewed)abstract
- Previous studies have suggested that the frequency of chromosomal aberrations (CAs), but not of sister chromatid exchanges (SCEs), predicts cancer risk. We have further examined this relationship in European cohorts comprising altogether almost 22,000 subjects, in the framework of a European collaborative project (CancerRiskBiomarkers). The present paper gives an overview of some of the results of the project, especially as regards CAs and SCEs. The results confirm that a high level of CAs is associated with an increased risk of cancer and indicate that this association does not depend on the time between CA analysis and cancer detection, i.e., is obviously not explained by undetected cancer. The present evidence indicates that both chromatid-type and chromosome-type CAs predict cancer, even though some data suggest that chromosome-type CAs may have a more pronounced predictive value than chromatid-type CAs. CA frequency appears to predict cancers at various sites, although there seems to be a particular association with gastrointestinal cancers. SCE frequency does not appear to have cancer predictive value, at least partly due to uncontrollable technical variation. A number of genetic polymorphisms of xenobiotic metabolism, DNA repair, and folate metabolism affect the level of CAs and might collectively contribute to the cancer predictivity of CAs. Other factors that may influence the association between CAs and cancer include, e.g., exposure to genotoxic carcinogens and internal generation of genotoxic species. Although the association between CA level and cancer is seen at the group level, an association probably also exists for the individual, although it is not known if an individual approach could be feasible. However, group level evidence should be enough to support the use of CA analysis as a tool in screening programs and prevention policies in occupational and environmental health.
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| 9. |
- Sun, Chengjun, et al.
(author)
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CRYAB-650 C>G (rs2234702) affects susceptibility to type 1 diabetes and IAA-positivity in Swedish population
- 2012
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In: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 73:7, s. 759-766
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Journal article (peer-reviewed)abstract
- BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.
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| 10. |
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| 11. |
- Berben, L, et al.
(author)
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Which interventions are used by healthcare professionals to enhance medication adherence in cardiovascular patients? : A survey of current clinical practice
- 2011
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In: European Journal of Cardiovascular Nursing. - : Oxford University Press (OUP). - 1474-5151 .- 1873-1953. ; 10:1, s. 14-21
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Journal article (peer-reviewed)abstract
- Background Complex medication regimens are often required to manage cardiovascular diseases. As non-adherence, which can have severe negative outcomes, is common among cardiovascular patients, various interventions to improve adherence should be implemented in daily practice.Aim To assess which strategies cardiovascular nurses and allied health professionals utilize to (1) assess patients' adherence to medication regimen, and (2) enhance medication adherence via educational/cognitive, counseling/behavioral, and psychological/affective interventions.Method A 45-item questionnaire to assess adherence assessment and interventional strategies utilized by health care professionals in daily clinical practice was distributed to a convenience sample of attendants of the 10th Annual Spring Meeting of the European Society of Cardiology Council on Cardiovascular Nursing and Allied Professions conference in Geneva (Switzerland) in March 2010. Respondents not in direct clinical practice were excluded. Descriptive statistics were used to describe practice patterns regarding adherence management.Results Of 276 distributed questionnaires, 171 (62%) were returned, of which 34 (20%) were excluded as respondents performed no direct patient care. Questioning patients about non-adherence during follow-up was the most frequently reported assessment strategy (56%). Educational/cognitive adherence enhancing interventions were used most frequently, followed by counseling/behavioral interventions. Psychological/affective interventions were less frequently used. The most frequent intervention used was providing reading materials (66%) followed by training patients regarding medication taking during inpatient recovery (48%). Slightly over two-thirds (69%) reported using a combination of interventions to improve patient's adherence.Conclusion Educational interventions are used most in clinical practice, although evidence shows they are less effective than behavioral interventions at enhancing medication adherence.
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| 12. |
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| 13. |
- Forsberg, A., et al.
(author)
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Once-only colonoscopy or two rounds of faecal immunochemical testing 2 years apart for colorectal cancer screening (SCREESCO): preliminary report of a randomised controlled trial
- 2022
-
In: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:6, s. 513-521
-
Journal article (peer-reviewed)abstract
- Background Screening for colorectal cancer is done with lower gastrointestinal endoscopy or stool-based tests. There is little evidence from randomised trials to show primary colonoscopy reduces mortality in colorectal cancer We aimed to investigate the effect of screening with once-only colonoscopy or two rounds of faecal immunochemical test screening on colorectal cancer mortality and incidence. Methods We did a randomised controlled trial in Sweden (SCREESCO). Residents in 18 of 21 regions who were age 60 years in the year of randomisation were identified from a population register maintained by the Swedish Tax Agency. A statistician with no further involvement in the trial used a randomised block method to assign individuals to once-only colonoscopy, two rounds of faecal immunochemical testing (OC-Sensor; 2 years apart), or a control group (no intervention; standard diagnostic pathways), in a ratio of 1:6 for colonoscopy versus control and 1:2 for faecal immunochemical testing versus control. Masking was not possible due to the nature of the trial. The primary endpoints of the trial are colorectal cancer mortality and colorectal cancer incidence. Here, we report preliminary participation rates, baseline findings, and adverse events from March, 2014, to December, 2020, in the two intervention groups after completion of recruitment and screening, up to the completion of the second faecal immunochemical testing round. Analyses were done in the intention-to-screen population, defined as all individuals who were randomly assigned to the respective study group. This study is registered with Clinical Trials.gov, NCT02078804. Findings Between March 1, 2014, and Dec 31, 2020, 278 280 people were induded in the study; 31 140 were assigned to the colonoscopy group, 60 300 to the faecal immunochemical test group, and 186 840 to the control group. 10 679 (35.1%) of 30 400 people who received an invitation for colonoscopy participated. 33 383 (55.5%) of 60 137 people who received a postal faecal immunochemical test participated. In the intention-to-screen analysis, colorectal cancer was detected in 49 (0.16%) of 31140 people in the colonoscopy group versus 121 (0. 20%) of 60 300 in the faecal immunochemical test group (relative risk [RR] 0.78, 95% CI 0.56-1.09). Advanced adenomas were detected in 637 (2.05%) people in the colonoscopy group and 968 (1.61%) in the faecal immunochemical test group (RR 1.27, 95% CI 1.15-1.41). Colonoscopy detected more right-sided advanced adenomas than faecal immunochemical testing. There were two perforations and 15 major bleeds in 16 555 colonoscopies. No intervention-related deaths occurred. Interpretation The diagnostic yield and the low number of adverse events indicate that the design from this trial, both for once-only colonoscopy and faecal immunochemical test screening, could be transferred to a population-based screening service if a benefit in disease-specific mortality is subsequently shown. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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| 14. |
- Hjorth-Hansen, H., et al.
(author)
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Safety and efficacy of the combination of pegylated interferon-alpha 2b and dasatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients
- 2016
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In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 30:9, s. 1853-1860
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Journal article (peer-reviewed)abstract
- Dasatinib (DAS) and interferon-a have antileukemic and immunostimulatory effects and induce deep responses in chronic myeloid leukemia (CML). We assigned 40 newly diagnosed chronic-phase CML patients to receive DAS 100 mg o.d. followed by addition of pegylated interferon-alpha 2b (PegIFN) after 3 months (M3). The starting dose of PegIFN was 15 mu g/week and it increased to 25 mu g/week at M6 until M15. The combination was well tolerated with manageable toxicity. Of the patients, 84% remained on PegIFN at M12 and 91% (DAS) and 73% (PegIFN) of assigned dose was given. Only one patient had a pleural effusion during first year, and three more during the second year. After introduction of PegIFN we observed a steep increase in response rates. Major molecular response was achieved in 10%, 57%, 84% and 89% of patients at M3, M6, M12 and M18, respectively. At M12, MR4 was achieved by 46% and MR4.5 by 27% of patients. No patients progressed to advanced phase. In conclusion, the combination treatment appeared safe with very promising efficacy. A randomized comparison of DAS +/- PegIFN is warranted.
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| 15. |
- Ilander, M, et al.
(author)
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Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia.
- 2017
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In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 31:5, s. 1108-1116
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Journal article (peer-reviewed)abstract
- Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse-free survival as patients with higher than median NK-cell percentage at the time of drug discontinuation had better probability to stay in remission. Similar association was not found with T or B cells or their subsets. In non-relapsing patients the NK-cell phenotype was mature, whereas patients with more naïve CD56(bright) NK cells had decreased relapse-free survival. In addition, the TNF-α/IFN-γ cytokine secretion by NK cells correlated with the successful drug discontinuation. Our results highlight the role of NK cells in sustaining remission and strengthen the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents.Leukemia advance online publication, 16 December 2016; doi:10.1038/leu.2016.360.
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| 16. |
- Lindvall, O, et al.
(author)
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Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up
- 1989
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In: Archives of Neurology. - : American Medical Association (AMA). - 0003-9942. ; 46:6, s. 31-615
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Journal article (peer-reviewed)abstract
- By using stereotaxic surgical techniques, ventral mesencephalic tissues from aborted human fetuses of 8 to 10 weeks' gestational age were implanted unilaterally into the striata in two patients with advanced Parkinson's disease. The patients were treated with a cyclosporine, azathioprine, and steroid regimen to minimize the risk for graft rejection. They were examined for 6 months preoperatively and 6 months postoperatively and continued to receive the same doses of antiparkinsonian medication. There were no significant postoperative complications. No major therapeutic effect from the operation was observed. However, in the clinical tests, both patients showed small but significant increases of movement speed for repeated pronation-supination, fist clenching, and foot lifting. The rate of walking also increased in the one patient tested. For both patients, there was an initial worsening postoperatively, followed by improvement vs preoperative performance at 1 to 3 months. Both patients also showed significant improvement in the magnitude of response to a single dose of levodopa (L-dopa), but there was no increase in the duration of drug action. The motor readiness potential increased in both patients postoperatively, primarily over the operated hemisphere. Neurophysiological measurements also showed a more rapid performance of simple and complex arm and hand movements on the side contralateral to transplantation in one patient at 5 months postoperatively. Positron emission tomography demonstrated no increased uptake of 6-L-(18F)-fluorodopa in the transplanted striatum at 5 and 6 months. Taken together, these results suggest that the fetal nigral implants may have provided a modest improvement in motor function, consistent with the presence of small surviving grafts. Although our results support further scientific experimentation with transplantation in Parkinson's disease, widespread clinical trials with this procedure are probably not warranted at this time.
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| 17. |
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| 18. |
- Prakobphol, A, et al.
(author)
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Salivary agglutinin, which binds Streptococcus mutans and Helicobacter pylori, is the lung scavenger receptor cysteine-rich protein gp-340.
- 2000
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In: The Journal of biological chemistry. - 0021-9258 .- 1083-351X. ; 275:51, s. 39860-6
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Journal article (peer-reviewed)abstract
- Salivary agglutinin is a high molecular mass component of human saliva that binds Streptococcus mutans, an oral bacterium implicated in dental caries. To study its protein sequence, we isolated the agglutinin from human parotid saliva. After trypsin digestion, a portion was analyzed by matrix-assisted laser/desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), which gave the molecular mass of 14 unique peptides. The remainder of the digest was subjected to high performance liquid chromatography, and the separated peptides were analyzed by MALDI-TOF/post-source decay; the spectra gave the sequences of five peptides. The molecular mass and peptide sequence information showed that salivary agglutinin peptides were identical to sequences in lung (lavage) gp-340, a member of the scavenger receptor cysteine-rich protein family. Immunoblotting with antibodies that specifically recognized either lung gp-340 or the agglutinin confirmed that the salivary agglutinin was gp-340. Immunoblotting with an antibody specific to the sialyl Le(x) carbohydrate epitope detected expression on the salivary but not the lung glycoprotein, possible evidence of different glycoforms. The salivary agglutinin also interacted with Helicobacter pylori, implicated in gastritis and peptic ulcer disease, Streptococcus agalactiae, implicated in neonatal meningitis, and several oral commensal streptococci. These results identify the salivary agglutinin as gp-340 and suggest it binds bacteria that are important determinants of either the oral ecology or systemic diseases.
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| 19. |
- Riegel, Barbara, et al.
(author)
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Development and initial testing of the self-care of chronic illness inventory
- 2018
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In: Journal of Advanced Nursing. - : WILEY. - 0309-2402 .- 1365-2648. ; 74:10, s. 2465-2476
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Journal article (peer-reviewed)abstract
- Aim: The aim was to develop and psychometrically test the self-care of chronic illness Inventory, a generic measure of self-care. Background: Existing measures of self-care are disease-specific or behaviour-specific; no generic measure of self-care exists. Design: Cross-sectional survey. Methods: We developed a 20-item self-report instrument based on the Middle Range Theory of Self-Care of Chronic Illness, with three separate scales measuring Self-Care Maintenance, Self-Care Monitoring, and Self-Care Management. Each of the three scales is scored separately and standardized 0-100 with higher scores indicating better self-care. After demonstrating content validity, psychometric testing was conducted in a convenience sample of 407 adults (enrolled from inpatient and outpatient settings at five sites in the United States and ResearchMatch.org). Dimensionality testing with confirmatory factor analysis preceded reliability testing. Results: The Self-Care Maintenance scale (eight items, two dimensions: illnessrelated and health-promoting behaviour) fit well when tested with a two-factor confirmatory model. The Self-Care Monitoring scale (five items, single factor) fitted well. The Self-Care Management scale (seven items, two factors: autonomous and consulting behaviour), when tested with a two-factor confirmatory model, fitted adequately. A simultaneous confirmatory factor analysis on the combined set of items supported the more general model. Conclusion: The self-care of chronic illness inventory is adequate in reliability and validity. We suggest further testing in diverse populations of patients with chronic illnesses.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Albin, Maria, et al.
(author)
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Retention patterns of asbestos fibres in lung tissue among asbestos cement workers
- 1994
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In: Occupational and Environmental Medicine. - 1470-7926. ; 51:3, s. 205-211
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Journal article (peer-reviewed)abstract
- Retention patterns in lung tissue (determined by transmission electron microscopy and energy dispersive spectrometry) of chrysotile, tremolite, and crocidolite fibres were analysed in 69 dead asbestos cement workers and 96 referents. There was an accumulation of tremolite with time of employment. Among workers who died within three years of the end of exposure, the 13 with high tremolite concentrations had a significantly longer duration of exposure than seven in a low to intermediate category (medians 32 v 20 years; p = 0.018, one sided). Crocidolite showed similar patterns of accumulation. In workers who died more than three years after the end of exposure, there were no correlations between concentrations of amphibole fibres and time between the end of exposure and death. Chrysotile concentrations among workers who died shortly after the end of exposure were higher than among the referents (median difference in concentrations 13 million fibres (f)/g dry weight; p = 0.033, one sided). No quantitative differences in exposure (duration or intensity) could be shown between workers with high and low to intermediate concentrations. Interestingly, all seven workers who had had a high intensity at the end of exposure (> 2.5 f/ml), had low to intermediate chrysotile concentrations at death, whereas those with low exposure were evenly distributed (31 subjects in both concentration categories); hence, there was a dependence between last intensity of exposure and chrysotile concentration (p = 0.014). Among 14 workers with a high average intensity of exposure, both those (n = 5) with high tissue concentrations of chrysotile and those (n = 10) with high tissue concentrations of tremolite fibres had more pronounced fibrosis than those with low to intermediate concentrations (median fibrosis grades for chrysotile: 2 v 1, p = 0.021; for tremolite: 2 v 0.5, p = 0.012). Additionally, workers who died shortly after the end of exposure with high concentrations of chrysotile and crocidolite had smoked more than those with low intermediate concentrations (medians for chrysotile 35 v 15 pack-years, p = 0.030; for crocidolite 37 v 15 pack-years, p = 0.012). The present data indicate that chrysotile has a relatively rapid turnover in human lungs, whereas the amphiboles, tremolite and crocidolite, have a slower turnover. Further, chrysotile retention may be dependent on dose rate. Chrysotile and crocidolite deposition and retention may be increased by tobacco smoking; chrysotile and tremolite by fibrosis.
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| 25. |
- Andreae, Christina, 1969-, et al.
(author)
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Changes in Appetite During the Heart Failure Trajectory and Association With Fatigue, Depressive Symptoms, and Quality of Life
- 2021
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In: Journal of Cardiovascular Nursing. - : Lippincott Williams & Wilkins. - 0889-4655 .- 1550-5049. ; 36:6, s. 539-545
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Journal article (peer-reviewed)abstract
- BACKGROUND: Decreased appetite can contribute to malnutrition in patients with heart failure (HF). Little is known about the trajectory of appetite over time in patients with HF and the factors associated with decreased appetite after discharge from the hospital.OBJECTIVE: The aims of this study were to investigate changes in appetite over time and explore how fatigue, depressive symptoms, and quality of life are associated with decreased appetite.METHODS: Data from the multicenter randomized Coordinating study evaluating Outcomes of Advising and Counseling in Heart Failure were used. Logistic regression and mixed-effects logistic regression were used to investigate changes in appetite over time and to explore the relationship between appetite and fatigue, depressive symptoms, and quality of life.RESULTS: A total of 734 patients with HF (mean age, 69 years) were included. Decreased appetite was present at all follow-up measurements; however, decreased appetite was significantly lower at the 1-month (odds ratio [OR], 0.43; confidence interval [CI], 0.29-0.63), 6-month (OR, 0.31; CI, 0.20-0.47), 12-month (OR, 0.22; CI, 0.14-0.34), and 18-month (OR, 0.24; CI, 0.15-0.37) follow-ups compared with baseline. Decreased appetite was associated with fatigue (OR, 3.09; CI, 1.98-4.84), depressive symptoms (OR, 1.76; CI, 1.35-2.29), and low quality of life (OR, 1.01; CI, 1.01-1.02) across all measurement points adjusted for covariates.CONCLUSIONS: Appetite improved after discharge; however, at all time points, at least 22% of patients reported decreased appetite. Fatigue, depressive symptoms, and low quality of life are factors associated with decreased appetite. Decreased appetite is a long-standing problem in that it does not disappear spontaneously after an acute HF deterioration.
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| 26. |
- Andreae, Christina, 1969-, et al.
(author)
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Depressive Symptoms Moderate the Association Between Appetite and Health Status in Patients With Heart Failure
- 2018
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In: Journal of Cardiovascular Nursing. - : Lippincott Williams & Wilkins. - 0889-4655 .- 1550-5049. ; 33:2, s. E15-E20
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Journal article (peer-reviewed)abstract
- Background: Decreased appetite and depressive symptoms are clinical problems in patients with heart failure. Both may result in impaired health status. Objective: The aims of this study were to investigate the association between appetite and health status in patients with heart failure and to explore whether depressive symptoms moderate this association. Methods: In this cross-sectional study, patients with heart failure (n = 186; mean age, 71 years), New York Heart Association class II to IV, participated. Data on appetite (Council of Nutrition Appetite Questionnaire), depressive symptoms (Patient Health Questionnaire-9), and health status (EQ-5D 3-level scale [EQ-5D-3L] descriptive system, EQ-5D-3L index, and EQ Visual Analog Scale) were collected by self-rating questionnaires. Pearson correlation was used to investigate the association between appetite and health status. Multiple regression was performed to examine whether depressive symptoms moderate the association between appetite and health status. Results: There was a significant association between appetite and health status for EQ-5D-3L descriptive system, mobility (P < .001), pain/discomfort (P < .001), and anxiety/depression (P < .001). This association was also shown in EQ-5D-3L index (P < .001) and EQ Visual Analog Scale (P < .001). Simple slope analysis showed that the association between appetite and health status was only significant for patients without depressive symptoms (B = 0.32, t = 4.66, P < .001). Conclusions: Higher level of appetite was associated with better health status. In moderation analysis, the association was presented for patients without depressive symptoms. Decreased appetite is an important sign of poor health status. To improve health status, health professionals should have greater attention on appetite, as well on signs of depressive symptoms.
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| 27. |
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| 28. |
- Andreae, Christina, et al.
(author)
-
The relationship between physical activity and appetite in heart failure – A cross sectional study
- 2017
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In: European Journal of Heart Failure. - : John Wiley & Sons. - 1388-9842 .- 1879-0844. ; 19:S1, s. 135-135
-
Journal article (peer-reviewed)abstract
- Background: Physical activity and appetite are important for maintaining physical health. Yet, sedentary lifestyle and poor appetite are frequently observed in the heart failure (HF) population. However, the relationships between these phenomena are not yet clearly understood. Purpose: To investigate the relationship between physical activity and appetite in patients with stable HF.Methods: In this cross sectional study, a consecutive sample of 186 patients with confirmed HF with NYHA class II-IV (median age 72y, 70% men, NYHA class II 61%) participated in the study. Patients were recruited from three HF outpatient clinics in central Sweden. Physical activity measures included total energy expenditure (TEE), active energy expenditure (AEE) above 3 METs, average daily METs and number of steps per day during four days using a validated multi-sensor wearable armband (SenseWear®, Body Monitoring System). Patients also self-reported their physical activity on a ten point numeric rating scale, from extremely low (1) to extremely high (10). Self-reported appetite was measured by Council on Nutrition Appetite Questionnaire (CNAQ), an 8-item instrument (score range 8-40) where CNAQ ≤28 indicate poor appetite. Associations between physical activity and appetite were analyzed by Spearman correlation while differences in physical activity between poor vs good appetite were analyzed using Mann Whitney U test.Results: There was a significant positive relationship between physical activity and appetite assessed by TEE (rs=.184, p=.012), AEE of moderate intensity >3 METs (rs=.262, p=.000), number of steps (rs=.292, p=.000), average METs intensity (rs=.249, p=.001), and self- reported physical activity (rs=.191, p =.009). Levels of physical activity in the low appetite group differed significantly from the group with better appetite, this was seen in all physical dimensions, TEE (U=3225, z=-2.26, p=.024), AEE (U=2902, z=-3.178, p=.001), number of steps (U=2706, z=-3.734, p=.000), average METs intensity (U=3128, z=-2.541, p=.011), levels of self-reported physical activity (U=3185, z=-2.47, p=.013).Conclusion: This study shows that physical activity is associated with appetite and that levels of physical activity differs between patients with poor and good appetite. These findings has implications for both research and practice and underlines the importance in monitoring both physical activity and appetite. Further research is needed to determine whether interventions targeting physical activity also improve appetite and vice versa in the HF population.
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| 29. |
- Axmon, Anna, et al.
(author)
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Miscarriages and stillbirths in women with a high intake of fish contaminated with persistent organochlorine compounds
- 2000
-
In: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 73:3, s. 204-208
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: The purpose of the present study was to assess the effect, on miscarriages and stillbirths, of persistent organochlorine compounds (POC) through dietary intake of fatty fish from the Baltic Sea. METHODS: Information on miscarriages and stillbirths was collected retrospectively by a self-administered questionnaire in a cohort of fishermen's wives from the Swedish east coast (by the Baltic Sea) and in a referent cohort of west coast fishermen's wives. Current fish consumption was used as a proxy for exposure within the east coast cohort. RESULTS: No increase in miscarriages or stillbirths was found in the east coast cohort compared with the west coast group, in fact a decrease in early miscarriages was found (OR 0.48 [95% CI 0.26-0.92]). Moreover, no increase in risk was found for current high consumers of fatty fish within the east coast cohort. CONCLUSIONS: The present data provided no evidence that dietary POC exposure increases miscarriage and stillbirth rates.
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| 30. |
- Axmon, Anna, et al.
(author)
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Time to pregnancy and infertility among women with a high intake of fish contaminated with persistent organochlorine compounds
- 2000
-
In: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 26:3, s. 199-206
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: The purpose of this study was to assess the effect of persistent organochlorine compounds through the dietary intake of fatty fish from the Baltic Sea on human fertility. METHODS: Information on time to pregnancy, subfertility, and infertility was collected retrospectively by self-administered questionnaires in 2 cohorts of fishermen's wives from the Swedish east (by the Baltic Sea) and west coasts. In addition to cohort affiliation, current fish consumption and growing up in a fishing village were used as proxies for exposure within the eastcoast cohort. RESULTS: A decreased success (ie, pregnancy) rate and a tendency towards increased subfertility was found for heavy smokers (> or =10 cigarettes/day) in the eastcoast cohort as compared with the westcoast cohort [success rate ratio 0.66, 95% confidence interval (95% CI) 0.49-.89; subfertility odds ratio 1.64, 95% CI 0.91-2.91). However, internal analyses within the eastcoast cohort did not show that growing up in a fishing village or high current fish consumption decreased the success rate. Eastcoast cohort affiliation showed an increased risk for infertility (odds ratio 2.49, 95% CI 1.05-5.92). CONCLUSIONS: The present data give some support for a negative association between exposure to persistent organochlorine compounds and fertility among heavy smokers. However, when the proxy exposure measures are also considered, the findings are not consistent. Better individual exposure assessments should be used before more firm conclusions are drawn.
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| 31. |
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| 32. |
- Badia, J. D., et al.
(author)
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Water absorption and hydrothermal performance of PHBV/sisal biocomposites
- 2014
-
In: Polymer degradation and stability. - : Elsevier BV. - 0141-3910 .- 1873-2321. ; 108, s. 166-174
-
Journal article (peer-reviewed)abstract
- The performance of biocomposites of poly(hydroxybutyrate-co-valerate) (PHBV) and sisal fibre subjected to hydrothermal tests at different temperatures above the glass transition of PHBV (T-H = 26, 36 and 46 degrees C) was evaluated in this study. The influences of both the fibre content and presence of coupling agent were focused. The water absorption capability and water diffusion rate were considered for a statistical factorial analysis. Afterwards, the physico-chemical properties of water-saturated biocomposites were assessed by Fourier-Transform Infrared Analysis, Size Exclusion Chromatography, Differential Scanning Calorimetry and Scanning Electron Microscopy. It was found that the water diffusion rate increased with both temperature and percentage of fibre, whereas the amount of absorbed water was only influenced by fibre content. The use of coupling agent was only relevant at the initial stages of the hydrothermal test, giving an increase in the diffusion rate. Although the chemical structure and thermal properties of water-saturated biocomposites remained practically intact, the physical performance was considerably affected, due to the swelling of fibres, which internally blew-up the PHBV matrix, provoking cracks and fibre detachment.
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| 33. |
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| 34. |
- Birgegård, Gunnar, 1944-, et al.
(author)
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Serum ferritin during infection : A longitudinal study
- 1978
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In: Scandinavian journal of haematology. - 0036-553X. ; 21:4, s. 333-340
-
Journal article (peer-reviewed)abstract
- Serum ferritin, transferrin, iron and haptoglobin have been investigated in a longitudinal study in 18 patients hospitalized for various acute infections. Within a couple of days after the onset of an infection, a rise in serum ferritin was seen, the magnitude of which was not dependent on the type of infection (bacterial or viral). The serum ferritin level remained elevated for several weeks in some patients, and 7 out of the 18 patients still had abnormally high values 5 weeks after the onset of illness. The mean curves for serum ferritin and the acute phase reactant haptoglobin were parallel. Possible mechanisms causing the elevation in serum ferritin are discussed.
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| 35. |
- Björk, Jonas, et al.
(author)
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Are occupational, hobby, or lifestyle exposures associated with Philadelphia chromosome positive chronic myeloid leukaemia?
- 2001
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In: Occupational and Environmental Medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 58:11, s. 722-727
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: To investigate a broad range of occupational, hobby, and lifestyle exposures, suggested as risk factors for Philadelphia chromosome positive (Ph+) chronic myeloid leukaemia (CML). METHODS: A case-control study, comprising 255 Ph+CML patients from southern Sweden and matched controls, was conducted. Individual data on work tasks, hobbies, and lifestyle exposures were obtained by telephone interviews. Occupational hygienists assessed occupational and hobby exposures for each subject individually. Also, occupational titles were obtained from national registries, and group level exposure-that is, the exposure proportion for each occupational title-was assessed with a job exposure matrix. The effects of 11 exposures using individual data and two exposures using group data (organic solvents and animal dust) were estimated. RESULTS: For the individual data on organic solvents, an effect was found for moderate or high intensity of exposure (odds ratio (OR) 3.4, 95% confidence interval (95% CI) 1.1 to 11) and for long duration (15-20 years) of exposure (OR 2.1, 95% CI 1.1 to 4.0). By contrast, the group data showed no association (OR 0.69, 95% CI 0.27 to 1.8; moderate or high intensity versus no exposure). For extremely low frequency electromagnetic fields (EMFs), only individual data were available. An association with long occupational exposure to EMFs was found (OR 2.3, 95% CI 1.2 to 4.5). However, no effect of EMF intensity was indicated. No significant effects of benzene, gasoline or diesel, or tobacco smoking were found. OR estimates below unity were suggested for personal use of hair dye and for agricultural exposures. CONCLUSIONS: Associations between exposure to organic solvents and EMFs, and Ph+CML were indicated but were not entirely consistent.
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| 36. |
- Borenäs, Marcus, et al.
(author)
-
ALK signaling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition
- 2024
-
In: Proceedings of the National Academy of Sciences of the United States of America. - 1091-6490. ; 121:1
-
Journal article (peer-reviewed)abstract
- High-risk neuroblastoma (NB) is a significant clinical challenge. MYCN and Anaplastic Lymphoma Kinase (ALK), which are often involved in high-risk NB, lead to increased replication stress in cancer cells, suggesting therapeutic strategies. We previously identified an ATR (ataxia telangiectasia and Rad3-related)/ALK inhibitor (ATRi/ALKi) combination as such a strategy in two independent genetically modified mouse NB models. Here, we identify an underlying molecular mechanism, in which ALK signaling leads to phosphorylation of ATR and CHK1, supporting an effective DNA damage response. The importance of ALK inhibition is supported by mouse data, in which ATRi monotreatment resulted in a robust initial response, but subsequent relapse, in contrast to a 14-d ALKi/ATRi combination treatment that resulted in a robust and sustained response. Finally, we show that the remarkable response to the 14-d combined ATR/ALK inhibition protocol reflects a robust differentiation response, reprogramming tumor cells to a neuronal/Schwann cell lineage identity. Our results identify an ability of ATR inhibition to promote NB differentiation and underscore the importance of further exploring combined ALK/ATR inhibition in NB, particularly in high-risk patient groups with oncogene-induced replication stress.
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| 37. |
- Buck, Harleah G., et al.
(author)
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A systematic review of heart failure dyadic self-care interventions focusing on intervention components, contexts, and outcomes
- 2018
-
In: International Journal of Nursing Studies. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0020-7489 .- 1873-491X. ; 77, s. 232-242
-
Research review (peer-reviewed)abstract
- Background: Having support from an informal carer is important for heart failure patients. Carers have the potential to improve patient self-care. At the same time, it should be acknowledged that caregiving could affect the carer negatively and cause emotional reactions of burden and stress. Dyadic (patient and informal carer) heart failure self-care interventions seek to improve patient self-care such as adherence to medical treatment, exercise training, symptom monitoring and symptom management when needed. Currently, no systematic assessment of dyadic interventions has been conducted with a focus on describing components, examining physical and delivery contexts, or determining the effect on patient and/or carer outcomes. Objective: To examine the components, context, and outcomes of dyadic self-care interventions. Design: A systematic review registered in PROSPERO, following PRISMA guidelines with a narrative analysis and realist synthesis. Data Sources: PubMed, EMBASE, Web of Science, PsycINFO, and Cochrane Central Register of Controlled Trials were searched using MeSH, EMTREE terms, keywords, and keyword phrases for the following concepts: dyadic, carers, heart failure and intervention. Eligible studies were original research, written in English, on dyadic self-care interventions in adult samples. Review methods: We used a two-tiered analytic approach including both completed studies with power to determine outcomes and ongoing studies including abstracts, small pilot studies and protocols to forecast future directions. Results: Eighteen papers - 12 unique, completed intervention studies (two quasi- and ten experimental trials) from 2000 to 2016 were reviewed. Intervention components fell into three groups education, support, and guidance. Interventions were implemented in 5 countries, across multiple settings of care, and involved 3 delivery modes face to face, telephone or technology based. Dyadic intervention effects on cognitive, behavioral, affective and health services utilization outcomes were found within studies. However, findings across studies were inconclusive as some studies reported positive and some non-sustaining outcomes on the same variables. All the included papers had methodological limitations including insufficient sample size, mixed intervention effects and counter-intuitive outcomes. Conclusions: We found that the evidence from dyadic interventions to promote heart failure self-care, while growing, is still very limited. Future research needs to involve advanced sample size justification, innovative solutions to increase and sustain behavior change, and use of mixed methods for capturing a more holistic picture of effects in clinical practice.
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| 38. |
- Bäckström, Torbjörn, et al.
(author)
-
Allopregnanolone and mood disorders
- 2014
-
In: Progress in Neurobiology. - : Elsevier BV. - 0301-0082 .- 1873-5118. ; 113, s. 88-94
-
Journal article (peer-reviewed)abstract
- Certain women experience negative mood symptoms during the menstrual cycle and progesterone addition in estrogen treatments. In women with PMDD increased negative mood symptoms related to allopregnanolone increase during the luteal phase of ovulatory menstrual cycles. In anovulatory cycles no symptom or sex steroid increase occurs. This is unexpected as positive modulators of the GABA-A receptor are generally increasing mood. This paradoxical effect has brought forward a hypothesis that the symptoms are provoked by allopregnanolone the GABA-A receptor system. GABA-A is the major inhibitory system in the brain. Positive modulators of the GABA-A receptor include the progesterone metabolites allopregnanolone and pregnanolone, benzodiazepines, barbiturates, and alcohol. GABA-A receptor modulators are known, in low concentrations to induce adverse, anxiogenic effects whereas in higher concentrations show beneficial, calming properties. Positive GABA-A receptor modulators induce strong paradoxical effects e.g. negative mood in 3-8% of those exposed, while up to 25% have moderate symptoms thus similar as the prevalence of PMDD, 3-8% among women in fertile ages, and up to 25% have moderate symptoms of premenstrual syndrome (PMS). The mechanism behind paradoxical reaction might be similar among them who react on positive GABA-A receptor modulators and in women with PMDD. In women the severity of these mood symptoms are related to the allopregnanolone serum concentrations in an inverted U-shaped curve. Negative mood symptoms occur when the serum concentration of allopregnanolone is similar to endogenous luteal phase levels, while low and high concentrations have less effect on mood. Low to moderate progesterone/allopregnanolone concentrations in women increases the activity in the amygdala (measured with fMRI) similar to the changes seen during anxiety reactions. Higher concentrations give decreased amygdala activity similar as seen during benzodiazepine treatment with calming anxiolytic effects. Patients with PMDD show decreased sensitivity in GABA-A receptor sensitivity to diazepam and pregnanolone while increased sensitivity to allopregnanolone. This agrees with findings in animals showing a relation between changes in alpha4 and delta subunits of the GABA-A receptor and anxiogenic effects of allopregnanolone. Conclusion: These findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor.(c) 2013 Elsevier Ltd. All rights reserved.
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| 39. |
- Bäckström, Torbjörn, et al.
(author)
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Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons
- 2011
-
In: Neuroscience. - Oxford : Elsevier BV. - 0306-4522 .- 1873-7544. ; 191:Special issue, s. 46-54
-
Research review (peer-reviewed)abstract
- Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane C1(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhibition, and hence excitability. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain. (C) 2011 Published by Elsevier Ltd on behalf of IBRO.
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| 40. |
- Drobni, Mirva, et al.
(author)
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A host-derived pentapeptide affecting adhesion, proliferation and local pH in Streptococcus-Actinomyces biofilm communities.
- 2006
-
In: Infection and immunity.
-
Research review (pop. science, debate, etc.)abstract
- Salivary proline-rich proteins (PRPs) attach commensal Actinomyces and Streptococcus species to teeth. Here, gel filtration, mass spectrometry and Edman degradation were applied to show the release of a pentapeptide, RGRPQ, from PRP-1 upon proteolysis by Streptococcus gordonii. Moreover, synthetic RGRPQ and derivatives were used to investigate associated innate properties and responsible motifs. The RGRPQ peptide increased 2.5-fold the growth rate of S. gordonii via a Q-dependent sequence motif, and selectively stimulated oral colonization of this organism in a rat model in vivo. By contrast, growth of Streptococcus mutans, implicated in caries, was unaffected. While the entire RGRPQ sequence was required to block sucrose-induced pH-decrease by S. gordonii and S. mutans, the N-terminal Arg residue mediated pH-increase (i.e. ammonia production) by S. gordonii alone (which exhibits Arg catabolism to ammonia). Strains of commensal viridans streptococci exhibited PRP degradation and Arg catabolism, while cariogenic species did not. The RGRPQ peptide mediated via a differential Q-dependent sequence motif, adhesion inhibition and desorption of PRP-1-binding strains of A. naeslundii genospecies 2 (5 out of 10 strains) but not of S. gordonii (n=5). The inhibitable A. naeslundii strains alone displayed the same binding profile as S. gordonii to hybrid peptides terminating in RGRPQ or GQSPQ, derived from the middle or C-terminal segments of PRP-1. The present findings indicate the presence of a host-bacteria interaction where a host peptide released by bacterial proteolysis affects key properties in biofilm formation.
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| 41. |
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| 42. |
- El Missiry, Mohamed, et al.
(author)
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Assessment of bone marrow lymphocytic status during tyrosine kinase inhibitor therapy and its relation to therapy response in chronic myeloid leukaemia
- 2016
-
In: Journal of Cancer Research and Clinical Oncology. - : Springer Science and Business Media LLC. - 0171-5216 .- 1432-1335. ; 142:5, s. 1041-1050
-
Journal article (peer-reviewed)abstract
- Tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukaemia have been reported to induce immunomodulatory effects. We aimed to assess peripheral blood (PB) and bone marrow (BM) lymphocyte status at the diagnosis and during different TKI therapies and correlate it with treatment responses. BM and PB samples were acquired from 105 first-line TKI-treated patients. Relative number of BM lymphocytes was evaluated from MGG-stained BM aspirates, and immunophenotypic analyses were performed with multicolour flow cytometry. Early 3-month expansion of BM lymphocytes was found during all different TKIs (imatinib n = 71, 20 %; dasatinib n = 25, 21 %; nilotinib n = 9, 22 %; healthy controls n = 14, 12 %, p < 0.0001). Increased PB lymphocyte count was only observed during dasatinib therapy. The BM lymphocyte expansion was associated with early molecular response; patients with 3-month BCR-ABL1 < 10 % showed higher lymphocyte counts than patients with BCR-ABL1 > 10 % (23 vs. 17 %, p < 0.05). Detailed phenotypic analysis showed that BM lymphocyte expansion consisted of various lymphocyte subclasses, but especially the proportion of CD19+ B cells and CD3negCD16/56+ NK cells increased from diagnostic values. During dasatinib treatment, the lymphocyte balance in both BM and PB was shifted more to cytotoxic direction (increased CD8+CD57+ and CD8+HLA-DR+ cells, and low T regulatory cells), whereas no major immunophenotypic differences were observed between imatinib and nilotinib patients. Early BM lymphocytosis occurs with all current first-line TKIs and is associated with better treatment responses. PB and BM immunoprofile during dasatinib treatment markedly differs from both imatinib- and nilotinib-treated patients.
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| 43. |
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| 44. |
- Enarsson, Karin, 1975, et al.
(author)
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Differential mechanisms for T lymphocyte recruitment in normal and neoplastic human gastric mucosa
- 2006
-
In: Clin Immunol. - : Elsevier BV. ; 118:1, s. 24-34
-
Research review (peer-reviewed)abstract
- Worldwide, gastric adenocarcinoma (GC) is the second most common cause of death from malignant disease. The reason why immune responses are unable to clear the tumour is not fully understood, although aberrant lymphocyte recruitment to the tumour site might be one factor. Therefore, we investigated the homing phenotype of mucosal T lymphocytes in GC, compared to tumour-free mucosa. We could detect significantly decreased frequencies of mucosal homing alpha4beta7+ T cells in the tumour tissues and increased frequencies of L-selectin+ T cells. This was probably due to the correlated decrease in MAdCAM-1 positive and increase in PNAd positive blood vessels in the tumour mucosa. There were also fewer CXCR3+ T lymphocytes in the tumour tissue. These findings provide evidence that endothelial cells within tumours arising at mucosal sites do not support extravasation of typical mucosa-infiltrating T cells. This may be of major relevance for future immunotherapeutic strategies for treatment of GC.
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| 45. |
- Enerbäck, Hanna, et al.
(author)
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Effect of high-fluoride toothpaste and mouth rinse on the prevention of demineralized lesions during orthodontic treatment: a randomized controlled trial
- 2023
-
In: European Journal of Orthodontics. - : Oxford University Press. - 0141-5387 .- 1460-2210. ; 45:5, s. 477-484
-
Journal article (peer-reviewed)abstract
- Objective To evaluate the effect of high-fluoride mouth rinse and high-fluoride toothpaste on the development of demineralized lesions (DLs) during orthodontic treatment. Trial design Three-armed parallel-group randomized controlled trial. Methods The trial was performed with 270 adolescent orthodontic patients. Randomization was performed in blocks of 30, enrolling the patients into one of the following groups: the fluoride mouth rinse (FMR) group receiving 0.2% sodium fluoride (NaF) mouth rinse plus 1450 ppm fluoride (F) toothpaste; high-fluoride toothpaste (HFT) group receiving 5000 ppm F toothpaste; and the Control (CTR) group receiving 1450 ppm F toothpaste. Inclusion criteria were patients scheduled for treatment in both arches with fixed appliances and age between 12 and 20 years. The primary outcome variable was the proportion of participants with at least one new demineralized lesion as assessed on digital photos taken before and after treatment, analysed by a blinded clinician. The analysis included all teeth or teeth in the aesthetic zone, i.e. all central incisors, lateral incisors, and canines. A random sample of 30 participants was assessed to check intra- and inter-reliability. For pairwise comparison between groups, Fisher's non-parametric permutation test was used for continuous variables. Blinding was employed during the caries registration and data analysis. Recruitment October 2010 to December 2012 Results In total, 270 patients were randomized, of which 22 were excluded during treatment. Therefore, 248 participants were included in the study. The number of patients with an increase of & GE;1 DL, including only central- and lateral incisors and canines, during orthodontic treatment, was significantly lower in the HFT group, 51/85 60%, compared to the CTR group, 64/82 78%, RR 0.77 (CI 0.62; 0.95), P = .01 and in the FMR group, 47/81 58%, compared to the CTR group, RR 0.74 (CI 0.60; 0.92), P < .01. Conclusions To prevent demineralized lesions in the aesthetic zone, high-fluoride mouth rinse and high-fluoride toothpaste may be recommended. Limitations The protocol was not registered, and the present study did not use a double-blinded design.
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| 46. |
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| 47. |
- Grimvall, E, et al.
(author)
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Monitoring of polychlorinated biphenyls in human blood plasma: methodological developments and influence of age, lactation, and fish consumption
- 1997
-
In: Archives of Environmental Contamination and Toxicology. - : Springer Science and Business Media LLC. - 0090-4341 .- 1432-0703. ; 32:3, s. 329-336
-
Journal article (peer-reviewed)abstract
- Human plasma samples from 50 wives of fishermen have been analyzed with respect to PCBs. The non-ortho-substituted PCB congeners CB-126 and CB-169 were determined by mass spectrometry in negative ion chemical ionization mode, which demonstrated a limit of detection of 30 fg. The recoveries of the internal standards used for determination of ortho-substituted CBs were approximately 95%. Two methods, one gravimetric and the other based on enzymatic determinations of triglycerides, cholesterol and phospholipids, were compared for the determination of total amount of lipids in the plasma samples; the correlation coefficient was 0.82 and the slope 0.98. For practical reasons, enzymatic determinations are recommended for further use. The total, lipid-adjusted concentrations of PCBs in plasma were influenced by age, total lactation time and consumption of fatty fish from the Baltic Sea.
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| 48. |
- Gunnarsson, Niklas, et al.
(author)
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Increased prevalence of prior malignancies and autoimmune diseases in patients diagnosed with chronic myeloid leukemia
- 2016
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In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 30:7, s. 1562-1567
-
Journal article (peer-reviewed)abstract
- We recently reported an increased incidence of second malignancies in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKI). To elucidate whether this increase may be linked, not to TKI but rather to a hereditary or acquired susceptibility to develop cancer, we estimated the prevalence of malignancies, autoimmune disease (AD) and chronic inflammatory disease (CID) in CML patients prior to their CML diagnosis. Nationwide population-based registers were used to identify patients diagnosed with CML in Sweden 2002-2012 and to estimate the prevalence of other malignancies, AD and CID prior to their CML diagnosis. For each patient with CML, five matched controls were selected from the general population. Conditional logistic regression was used to calculate odds ratios (OR). Nine hundred and eighty-four CML patients were assessed, representing more than 45 000 person-years of follow-up. Compared with matched controls, the prevalence of prior malignancies and AD was elevated in CML patients: OR 1.47 (95% confidence interval (CI) 1.20-1.82) and 1.55 (95% CI 1.21-1.98), respectively. No associations were detected between CML and previous CID. An increased prevalence of other malignancies and AD prior to the diagnosis of CML suggest that a hereditary or acquired predisposition to cancer and/or autoimmunity is involved in the pathogenesis of CML.
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| 49. |
- Hallgren, C G, et al.
(author)
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Markers of high fish intake are associated with decreased risk of a first myocardial infarction
- 2001
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In: British Journal of Nutrition. - 1475-2662. ; 86:3, s. 397-404
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Journal article (peer-reviewed)abstract
- High intake of fish has been associated with reduced risk of CHD. The high content of n-3 polyunsaturated fatty acids (PUFA) in fish has been suggested to be a protective factor. In addition, fish is the entirely dominating source of methylmercury for the general population, and the concentration of Hg in erythrocytes (Ery-Hg) is often used as an index of fish consumption. Our aim was to study the relationships between a first-ever myocardial infarction, Ery-Hg, activity of gluthathione peroxidase in erythrocytes (Ery-GSH-Px) and plasma concentration of the n-3 PUFA eicosapentaenoic and docosahexaenoic acids (P-PUFA). In a population-based prospective nested case-control study within Northern Sweden seventy-eight cases of a first-ever myocardial infarction were compared with 156 controls with respect to Ery-Hg, P-PUFA and Ery-GSH-Px. Both Ery-Hg and P-PUFA, but not Ery-GSH-Px, were significantly higher in subjects reporting high fish intake (at least one meal per week) than in those with lower intake. This finding suggests that Ery-Hg and P-PUFA reflect previous long-term fish intake. Low risk of myocardial infarction was associated with high Ery-Hg or high P-PUFA. In a multivariate model the risk of myocardial infarction was further reduced in subjects with both high Ery-Hg and high P-PUFA (odds ratio 0.16, 95 % CI 0.04, 0.65). In conclusion, there is a strong inverse association between the risk of a first myocardial infarction and the biomarkers of fish intake, Ery-Hg and P-PUFA, and this association is independent of traditional risk factors.
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- Hansson, A C, et al.
(author)
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Corticosterone actions on the hippocampal brain-derived neurotrophic factor expression are mediated by exon IV promoter.
- 2006
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In: Journal of neuroendocrinology (Print). - : Wiley. - 0953-8194 .- 1365-2826. ; 18:2, s. 104-114
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Journal article (peer-reviewed)abstract
- Brain-derived neurotrophic factor (BDNF) expression is strongly regulated by adrenocorticosteroids via activated gluco- and mineralocorticoid receptors. Four separate promoters are located upstream of the BDNF noncoding exons I to IV and may thus be involved in adrenocorticosteroid-mediated gene regulation. In adrenalectomised rats, corticosterone (10 mg/kg s.c.) induces a robust down-regulation of both BDNF mRNA and protein levels in the hippocampus peaking at 2-8 h. To study the role of the individual promoters in the corticosterone response, we employed exon-specific riboprobe in situ hybridisation as well as real-time polymerase chain reaction (PCR) in the dentate gyrus. We found a down-regulation, mainly of exon IV and the protein-coding exon V, in nearby all hippocampal subregions, but exon II was only down-regulated in the dentate gyrus. Exon I and exon III transcripts were not affected by corticosterone treatment. The results could be confirmed with real-time PCR in the dentate gyrus. It appears as if the exon IV promoter is the major target for corticosterone-mediated transcriptional regulation of BDNF in the hippocampus.
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