| 1. |
- Brütt, Katharina, et al.
(författare)
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Competition and moral behavior: A meta-analysis of forty-five crowd-sourced experimental designs
- 2023
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Ingår i: Proceedings of the National Academy of Sciences - PNAS. - : National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 120:23
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Tidskriftsartikel (refereegranskat)abstract
- Does competition affect moral behavior? This fundamental question has been debated among leading scholars for centuries, and more recently, it has been tested in experimental studies yielding a body of rather inconclusive empirical evidence. A potential source of ambivalent empirical results on the same hypothesis is design heterogeneity-variation in true effect sizes across various reasonable experimental research protocols. To provide further evidence on whether competition affects moral behavior and to examine whether the generalizability of a single experimental study is jeopardized by design heterogeneity, we invited independent research teams to contribute experimental designs to a crowd-sourced project. In a large-scale online data collection, 18,123 experimental participants were randomly allocated to 45 randomly selected experimental designs out of 95 submitted designs. We find a small adverse effect of competition on moral behavior in a meta-analysis of the pooled data. The crowd-sourced design of our study allows for a clean identification and estimation of the variation in effect sizes above and beyond what could be expected due to sampling variance. We find substantial design heterogeneity-estimated to be about 1.6 times as large as the average standard error of effect size estimates of the 45 research designs-indicating that the informativeness and generalizability of results based on a single experimental design are limited. Drawing strong conclusions about the underlying hypotheses in the presence of substantive design heterogeneity requires moving toward much larger data collections on various experimental designs testing the same hypothesis.
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| 2. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 3. |
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| 4. |
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Bahmanyar, Shahram, et al.
(författare)
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Cystic fibrosis gene mutations and gastrointestinal diseases
- 2010
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Ingår i: Journal of Cystic Fibrosis. - : Elsevier BV. - 1569-1993 .- 1873-5010. ; 9:4, s. 288-291
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study examined if CF mutation heterozygosity is associated with diseases of gastrointestinal epithelial barrier function. Design and methods: Swedish registers identified 865 patients with a diagnosis of CF between 1968 and 2003 and matched with 8101 individuals without CF. Gastrointestinal disease risk was examined among 1534 biological parents and 1396 siblings of CF patients, compared with 15,526 parents and 15,542 siblings of individuals without CF. Results: First-degree relatives of CF patients were not at lower risk of the gastrointestinal diseases, in contrast with a raised risk among CF patients. Conclusion: Heterozygosity for CF gene mutations does not protect against gastrointestinal diseases where impaired barrier function may be relevant. (C) 2010 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
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| 9. |
- Berdan, Emma L, 1983, et al.
(författare)
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How chromosomal inversions reorient the evolutionary process
- 2023
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Ingår i: Journal of Evolutionary Biology. - 1010-061X .- 1420-9101. ; 36:12, s. 1761-1782
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Forskningsöversikt (refereegranskat)abstract
- Inversions are structural mutations that reverse the sequence of a chromosome seg-ment and reduce the effective rate of recombination in the heterozygous state. They play a major role in adaptation, as well as in other evolutionary processes such as spe-ciation. Although inversions have been studied since the 1920s, they remain difficult to investigate because the reduced recombination conferred by them strengthens the effects of drift and hitchhiking, which in turn can obscure signatures of selection. Nonetheless, numerous inversions have been found to be under selection. Given re-cent advances in population genetic theory and empirical study, here we review how different mechanisms of selection affect the evolution of inversions. A key difference between inversions and other mutations, such as single nucleotide variants, is that the fitness of an inversion may be affected by a larger number of frequently interacting processes. This considerably complicates the analysis of the causes underlying the evolution of inversions. We discuss the extent to which these mechanisms can be disentangled, and by which approach.
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| 10. |
- Bing, Vibeke, et al.
(författare)
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Det har både blivit lättare och svårare - om det nya i att arbeta på familjecentraler
- 2011
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Ingår i: Socialmedicinsk Tidskrift. - 0037-833X. ; 88:2, s. 133-143
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Den här artikeln utgår ifrån personalens perspektiv. Första delen är resultat från en enkätstudie som fokuserar på hur personal förändrat sitt sätt att arbeta sedan de började arbeta på familjecentral. De flesta upplever att eftersom de har andra professioner i samma hus lättare upptäcker familjer med extra behov av stöd och bättre kan fokusera på sina egna arbetsuppgifter. Som fördjupning av svaren i enkäten har olika personalkategorier ombetts skriva en kortfattad berättelse om sitt eget arbete på familjecentral. Sjuksköterskor, barnmorska, psykolog, socionom, förskollärare, bibliotekarie och samordnare berättar hur de arbetar. Slutsatserna från artikeln är att familjecentraler kan ses som ett svar på att stödet till blivande och småbarnsföräldrar har utökats på de områden som den traditionella mödra- och barnhälsovården har sett som problematisk att möta. Sannolikt ökar förutsättningarna för att de som behöver extra stöd också kan få möjlighet till detta under förutsättning att extra stöd finns när familjecentralens resurser inte räcker till.
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| 11. |
- Bing, Vibeke, et al.
(författare)
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Det har både blivit lättare och svårare - om det nya i att arbeta på familjecentraler
- 2011
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Ingår i: Socialmedicinsk Tidskrift. - 0037-833X. ; 88:2, s. 133-143
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Den här artikeln utgår ifrån personalens perspektiv. Första delen är resultat från en enkätstudie som fokuserar på hur personal förändrat sitt sätt att arbeta sedan de började arbeta på familjecentral. De flesta upplever att eftersom de har andra professioner i samma hus lättare upptäcker familjer med extra behov av stöd och bättre kan fokusera på sina egna arbetsuppgifter. Som fördjupning av svaren i enkäten har olika personalkategorier ombetts skriva en kortfattad berättelse om sitt eget arbete på familjecentral. Sjuksköterskor, barnmorska, psykolog, socionom, förskollärare, bibliotekarie och samordnare berättar hur de arbetar. Slutsatserna från artikeln är att familjecentraler kan ses som ett svar på att stödet till blivande och småbarnsföräldrar har utökats på de områden som den traditionella mödra- och barnhälsovården har sett som problematisk att möta. Sannolikt ökar förutsättningarna för att de som behöver extra stöd också kan få möjlighet till detta under förutsättning att extra stöd finns när familjecentralens resurser inte räcker till.
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| 12. |
- Castellani, Carlo, et al.
(författare)
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Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice
- 2008
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Ingår i: Journal of Cystic Fibrosis. - : Elsevier BV. - 1569-1993 .- 1873-5010. ; 7:3, s. 179-96
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Tidskriftsartikel (refereegranskat)abstract
- It is often challenging for the clinician interested in cystic fibrosis (CF) to interpret molecular genetic results, and to integrate them in the diagnostic process. The limitations of genotyping technology, the choice of mutations to be tested, and the clinical context in which the test is administered can all influence how genetic information is interpreted. This paper describes the conclusions of a consensus conference to address the use and interpretation of CF mutation analysis in clinical settings. Although the diagnosis of CF is usually straightforward, care needs to be exercised in the use and interpretation of genetic tests: genotype information is not the final arbiter of a clinical diagnosis of CF or CF transmembrane conductance regulator (CFTR) protein related disorders. The diagnosis of these conditions is primarily based on the clinical presentation, and is supported by evaluation of CFTR function (sweat testing, nasal potential difference) and genetic analysis. None of these features are sufficient on their own to make a diagnosis of CF or CFTR-related disorders. Broad genotype/phenotype associations are useful in epidemiological studies, but CFTR genotype does not accurately predict individual outcome. The use of CFTR genotype for prediction of prognosis in people with CF at the time of their diagnosis is not recommended. The importance of communication between clinicians and medical genetic laboratories is emphasized. The results of testing and their implications should be reported in a manner understandable to the clinicians caring for CF patients.
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| 13. |
- Ciofu, Oana, et al.
(författare)
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Investigation of the algT operon sequence in mucoid and non-mucoid Pseudomonas aeruginosa isolates from 115 Scandinavian patients with cystic fibrosis and in 88 in vitro non-mucoid revertants
- 2008
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Ingår i: Microbiology. - : Microbiology Society. - 1350-0872 .- 1465-2080. ; 154:Pt 1, s. 103-13
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Tidskriftsartikel (refereegranskat)abstract
- Pseudomonas aeruginosa is the dominant pathogen causing chronic lung infections in patients with cystic fibrosis (CF). After an initial phase characterized by intermittent colonizations, a chronic infection is established upon conversion of P. aeruginosa from the non-mucoid to the mucoid, alginate-overproducing phenotype. During the chronic infection the isolation of both mucoid and non-mucoid isolates in CF sputum samples is very common. The purpose of the present study was to establish, by sequence analysis, the types of mutations present in the algTmucABD operon in a large number of mucoid and non-mucoid P. aeruginosa isolates from Scandinavian CF patients and in in vitro-derived non-mucoid revertants. Mucoid (83) and non-mucoid isolates (103) from 91 Scandinavian patients with chronic P. aeruginosa infection and 24 non-mucoid isolates from intermittently colonized CF patients were investigated. In addition, 88 spontaneous non-mucoid revertants obtained in vitro from nine mucoid CF isolates were also included in the study. Mutations in mucA were found in 92 % of the mucoid and in up to 70 % of the non-mucoid isolates from chronically infected patients, indicating that the majority of non-mucoid isolates are revertants. None of the non-mucoid isolates from intermittently colonized CF patients harboured mucA mutations. Although algT has been considered an important gene for secondary-site mutations responsible for reversion to non-mucoidy, only 30 % of the mucA-mutated non-mucoid CF isolates had mutations in algT. In contrast, 83 % of the in vitro-derived spontaneous non-mucoid revertants had mutations in algT, showing that in the CF lung there is a selection for non-mucoid revertants with secondary-site mutations in genes other than algT. In addition, we report, to our knowledge for the first time, loss-of-function mutations in the negative regulators mucB and mucD in CF clinical isolates. In some of the CF isolates these mutations are associated with moderate alginate production. In conclusion, most non-mucoid isolates from chronically infected CF patients are revertants and the mechanism of revertance is algT-independent in the CF lung.
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| 14. |
- Dahlström, Märta, et al.
(författare)
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Development of a fluorescent intensity assay amenable for high-throughput screening for determining 15-lipoxygenase activity.
- 2010
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Ingår i: Journal of Biomolecular Screening. - : Elsevier BV. - 1087-0571 .- 1552-454X. ; 15:6, s. 671-9
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Tidskriftsartikel (refereegranskat)abstract
- 15-Lipoxygenase-1 catalyzes the introduction of molecular oxygen into polyunsaturated fatty acids to form a lipid hydroperoxide. The authors have developed an assay for the detection of lipid hydroperoxides formed by human 15-lipoxygenase (15-LO) in enzyme or cellular assays using either a 96-well or a 384-well format. The assays described take advantage of the ability of lipid hydroperoxides to oxidize nonfluorescent diphenyl-1-pyrenylphosphine (DPPP) to a fluorescent phosphine oxide. Oxidation of DPPP yields a fluorescent compound, which is not sensitive to temperature and is stable for more than 2 h. The assay is sensitive toward inhibition and robust with a Z' value of 0.79 and 0.4 in a 96- and 384-well format, respectively, and thus amenable for high-throughput screening. The utility of DPPP as a marker for 15-lipoxygenase activity was demonstrated with both enzyme- and cell-based assays for the identification of hits and to determine potency by IC(50) determinations.
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| 15. |
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| 16. |
- De Jode, Aurélien, et al.
(författare)
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Ten years of demographic modelling of divergence and speciation in the sea
- 2022
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Ingår i: Evolutionary Applications. - : Wiley. - 1752-4571. ; 16:2, s. 542-59
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Tidskriftsartikel (refereegranskat)abstract
- Understanding population divergence that eventually leads to speciation is essential for evolutionary biology. High species diversity in the sea was regarded as a paradox when strict allopatry was considered necessary for most speciation events because geographical barriers seemed largely absent in the sea, and many marine species have high dispersal capacities. Combining genome-wide data with demographic modelling to infer the demographic history of divergence has introduced new ways to address this classical issue. These models assume an ancestral population that splits into two subpopulations diverging according to different scenarios that allow tests for periods of gene flow. Models can also test for heterogeneities in population sizes and migration rates along the genome to account, respectively, for background selection and selection against introgressed ancestry. To investigate how barriers to gene flow arise in the sea, we compiled studies modelling the demographic history of divergence in marine organisms and extracted preferred demographic scenarios together with estimates of demographic parameters. These studies show that geographical barriers to gene flow do exist in the sea but that divergence can also occur without strict isolation. Heterogeneity of gene flow was detected in most population pairs suggesting the predominance of semipermeable barriers during divergence. We found a weak positive relationship between the fraction of the genome experiencing reduced gene flow and levels of genome-wide differentiation. Furthermore, we found that the upper bound of the ‘grey zone of speciation’ for our dataset extended beyond that found before, implying that gene flow between diverging taxa is possible at higher levels of divergence than previously thought. Finally, we list recommendations for further strengthening the use of demographic modelling in speciation research. These include a more balanced representation of taxa, more consistent and comprehensive modelling, clear reporting of results and simulation studies to rule out nonbiological explanations for general results.
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| 17. |
- Döring, Gerd, et al.
(författare)
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Clinical trials in cystic fibrosis
- 2007
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Ingår i: Journal of Cystic Fibrosis. - : Elsevier BV. - 1569-1993 .- 1873-5010. ; 6:2, s. 85-99
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Tidskriftsartikel (refereegranskat)abstract
- In patients with cystic fibrosis (CF), clinical trials are of paramount importance. Here, the current status of drug development in CF isdiscussed and future directions highlighted. Methods for pre-clinical testing of drugs with potential activity in CF patients including relevantanimal models are described. Study design options for phase II and phase III studies involving CF patients are provided, including requiredpatient numbers, safety issues and surrogate end point parameters for drugs, tested for different disease manifestations. Finally, regulatoryissues for licensing new therapies for CF patients are discussed, including new directives of the European Union and the structure of aEuropean clinical trial network for clinical studies involving CF patients is proposed.
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| 18. |
- Edenborough, F. P., et al.
(författare)
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Guidelines for the management of pregnancy in women with cystic fibrosis
- 2008
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Ingår i: Journal of Cystic Fibrosis. - : Elsevier BV. - 1569-1993 .- 1873-5010. ; 7 Suppl 1, s. S2-32
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Tidskriftsartikel (refereegranskat)abstract
- Women with cystic fibrosis (CF) now regularly survive into their reproductive years in good health and wish to have a baby. Many pregnancies have been reported in the literature and it is clear that whilst the outcome for the baby is generally good and some mothers do very well, others find either their CF complicates the pregnancy or is adversely affected by the pregnancy. For some, pregnancy may only become possible after transplantation. Optimal treatment of all aspects of CF needs to be maintained from the preconceptual period until after the baby is born. Clinicians must be prepared to modify their treatment to accommodate the changing physiology during pregnancy and to be aware of changing prescribing before conception, during pregnancy, after birth and during breast feeding. This supplement offers consensus guidelines based on review of the literature and experience of paediatricians, adult and transplant physicians, and nurses, physiotherapists, dietitians, pharmacists and psychologists experienced in CF and anaesthetist and obstetricians with experience of CF pregnancy. It is hoped they will provide practical guidelines helpful to the multidisciplinary CF teams caring for pregnant women with CF.
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| 19. |
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| 20. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 21. |
- Gustafsson, Ingegerd, et al.
(författare)
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Bacteria with increased mutation frequency and antibiotic resistance are enriched in the commensal flora of patients with high antibiotic usage
- 2003
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 52:4, s. 645-650
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We examined how prolonged antibiotic treatment affected the resistance and mutation frequency of human microflora isolated from intestine (Escherichia coli, enterococci spp.), pharynx (alpha-streptococci) and nostril (coagulase-negative staphylococci, CoNS).METHODS: Samples were collected from patients at the Center of Cystic Fibrosis (n=18) and the haematology ward (n=18) of the University Hospital, Uppsala, Sweden. The individually used amount of antibiotics for 1 year was recorded as the defined daily dose (DDD). Primary health care patients (n=30), with no antibiotic treatment for 1 year before sampling, were used as controls. Three isolates of each bacterium from each patient were examined. Antibiotic susceptibilities were determined by disc diffusion. Mutation frequencies to rifampicin resistance were measured on 30 independent cultures of each bacterial species from each individual by plating on rifampicin agar plates. For alpha-streptococci the mutation frequency to streptomycin resistance was also determined.RESULTS: Isolates from patients with high antibiotic use showed a pronounced shift towards increased resistance and a small but significant increase in the mutation frequency compared with isolates from the controls. For E. coli, enterococci and CoNS the increase in geometric mean mutation frequency in the patient group was 3-, 1.8- and 1.5-fold, respectively (P values 0.0001, 0.016 and 0.012). For alpha-streptococci there was a significant difference in geometric mean mutation frequency between patient and control groups for streptomycin resistance (P=0.024) but not for rifampicin resistance (P=0.74).CONCLUSIONS: High antibiotic use selected for commensals with highly increased resistance and a slight increase in mutation frequency.
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| 22. |
- Hellstrand Tang, Ulla, 1956, et al.
(författare)
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Clinical guidelines recommending prosthetics and orthotics in Sweden : Agreement between national and regional guidelines
- 2023
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Ingår i: Prosthetics and Orthotics International. - : Sage Publications. - 0309-3646 .- 1746-1553.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite the presence of both national and regional clinical practical guidelines (CPGs) in Sweden, no previous studies have investigated the quality of CPGs or the level of agreement between national and regional CPGs.OBJECTIVES: This study aimed to assess the quality of national CPGs recommending prosthetics and orthotics (P&O) and quantify the agreement between national and regional CPGs in Sweden.STUDY DESIGN: Literature Review.METHODS: National and regional CPGs were identified in public databases and by surveyed local nurse practitioners. Quality of the national guidelines was assessed by using AGREE II. Agreement between recommendations in the national and regional CPGs was quantified on a 4-grade rating scale ("similar," "partially similar," "not similar/not present," and "different").RESULTS: Of 18 national CPGs, 3 CPGs (CPGs of Diabetes, Musculoskeletal disorders, and Stroke) had 9 recommendations related to P&O. The Musculoskeletal disorders and Stroke CPGs had quality scores .60% in all domains, and the Diabetes CPG had scores .60% in 5 of 6 domains according to AGREE II. Seven regional CPGs for P&O treatment were identified. Three national recommendations (in Diabetes CPGs) showed "similar" content for all regions, and 2 national recommendations (in Diabetes CPGs) showed "not similar" content for all regions. The remaining recommendations (Diabetes, Musculoskeletal disorders, and Stroke CPGs) had varying agreement with regional CPGs. CONCLUSIONS: There is a limited number of national recommendations for treatment within P&O. There was variation in the agreement of P&O-related recommendations in national and regional CPGs, which might lead to unequal care throughout the national healthcare system.
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| 23. |
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| 26. |
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| 27. |
- Johannesson, Kerstin, 1955, et al.
(författare)
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Diverse pathways to speciation revealed by marine snails
- 2024
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Ingår i: Trends in Genetics. - 0168-9525 .- 1362-4555.
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Forskningsöversikt (refereegranskat)abstract
- Speciation is a key evolutionary process that is not yet fully understood. Combining population genomic and ecological data from multiple diverging pairs of marine snails (Littorina) supports the search for speciation mechanisms. Placing pairs on a one-dimensional speciation continuum, from undifferentiated populations to species, obscured the complexity of speciation. Adding multiple axes helped to describe either speciation routes or reproductive isolation in the snails. Divergent ecological selection repeatedly generated barriers between ecotypes, but appeared less important in completing speciation while genetic incompatibilities played a key role. Chromosomal inversions contributed to genomic barriers, but with variable impact. A multidimensional (hypercube) approach supported framing of questions and identification of knowledge gaps and can be useful to understand speciation in many other systems.
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| 28. |
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| 29. |
- Johannesson, Kerstin, 1955, et al.
(författare)
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Ten years of marine evolutionary biology - challenges and achievements of a multidisciplinary research initiative
- 2023
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Ingår i: Evolutionary Applications. - : Wiley. - 1752-4571. ; 16:2, s. 530-41
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Tidskriftsartikel (refereegranskat)abstract
- The Centre for Marine Evolutionary Biology (CeMEB) at the University of Gothenburg, Sweden, was established in 2008 through a 10-year research grant of 8.7 m€ to a team of senior researchers. Today, CeMEB members have contributed >500 scientific publications, 30 PhD theses and have organised 75 meetings and courses, including 18 three-day meetings and four conferences. What are the footprints of CeMEB, and how will the centre continue to play a national and international role as an important node of marine evolutionary research? In this perspective arcticle we first look back over the 10 years of CeMEB activities and briefly survey some of the many achievements of CeMEB. We furthermore compare the initial goals, as formulated in the grant application, with what has been achieved, and discuss challenges and milestones along the way. Finally, we bring forward some general lessons that can be learnt from a research funding of this type, and we take also look ahead, discussing how CeMEB’s achievements and lessons can be used as a springboard to the future of marine evolutionary biology.
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| 30. |
- Johannesson, Marie
(författare)
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Aspects on puberty and fertility among females with cystic fibrosis a multidisciplinary study on humans and rats
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Due to intensified symptomatic treatment, a majority of patients with cystic fibrosis (CF) now go through puberty and reach adulthood. This provides new challenges for the CF health care providers. Delayed puberty and decreased fertility seen in CF females have been suggested to be caused by malnutrition and impermeable cervical mucus resulting from defects in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The main purpose of this thesis was to highlight factors contributing to developmental and reproductive status by retrospectively studying pubertal development and prospectively studying pathophysiology behind reduced fertility in CF women. We also wanted to study psychosocial issues concerning puberty and motherhood among CF women, how they had obtained and conceived information in these matters and how they would like information to be given. CFTR and multidrug resistance (MDRlb) proteins are members of the "ATP-binding cassette" superfamily of transporters. They are associated with chloride channel activities and ATP secretion and have complementary patterns of expression in several organs. We wanted to study CFTR mRNA expression in hypothalamic areas important for sexual maturation and reproduction in female rats and whether CFTR resp. MDRlb mRNA expression in rat lung change during pregnancy. Pubertal delay still existed among CF women despite good clinical status. The more delayed puberty in patients homozygous for the most common mutation (delta F508) and those with pathological glucose tolerance test may be due to increased resting energy expenditure and defective insulin secretion. However, the low levels of essential fatty acids (EFA) is probably also a factor behind the delayed puberty. The cause of reduced fertility among these CF women appears more complex than previously thought. The data indicate that a primary ovarian disorder is involved. The unexpected high rate of anovulation in CF women with good clinical status may be explained by more profound EFA deficiency, signs of hyperinsulin secretion and higher androgen levels compared to the CF women who ovulate. However, all but one CF patient responded with ovulation to the clomiphene citrate stimulation treatment indicating a normal ovarian response. The high androgen levels and signs of hyperinsulinemia resemble that of women with polycystic ovarian syndrome. It is still possible that defective neuroendocrine regulation in CF may be one causative factor to disturbed hormonal balance in these women. CFTR mRNA was expressed in the medial preoptic area in hypothalamus in female rats addressing the possibility of CFTR regulation of sexual maturation and reproductive behaviour. CFTR mRNA was also found in cortical deep pyramidal layer V implying possible involvement of CFTR in "motor" function and output control over bodily movements and secretion. CFTR might act via acidification of synaptic vesicles and thereby regulate neurotransmission and secretion of neuropeptides. Disturbances in CFTR production in the brain regions observed could thus lead to impaired cerebral control over motor/visceral and endocrine systems and thereby accentuate pathology seen in CF patients. No variations in CFTR or MDRlb mRNA levels in the lungs during pregnancy were detected. However, there was an unusual degree of variation in MDRlb mRNA expression in lung parenchyma between animals in both the control and pregnant group. This may relate to humans, where increased expression in MDRI in the airways correlated with reduced lung symptomatology in a CF patient undergoing chemotherapy. A defective CFTR channel protein might be partly compensated by a functioning MDRI protein. Our study showed that CF females need special education and counseling concerning their health, pubertal development and fertility especially during the years of adolescence. Information about puberty and fertility should be given individually and in small discussion groups with teenage girls combined with thorough medical and psychological guidance concerning motherhood for the adult CF females.
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| 31. |
- Johannesson, Marie, et al.
(författare)
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Cancer risk among patients with cystic fibrosis and their first-degree relatives
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:12, s. 2953-2956
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Tidskriftsartikel (refereegranskat)abstract
- Patients with cystic fibrosis (CF) are at increased risk of some cancers. Little is known about the cancer risks among carriers heterozygous for the CF mutation and it is hypothesized this may be associated with reduced cancer risk. Using Swedish general population-based registers, we identified 884 patients with CF from 1968 to 2003 and 3,033 of their first-degree relatives The subjects were followed from birth of index persons or 1958, whichever came later, until death, emigration or 2003, whichever came first. Cancer risks were compared with the general Swedish population using standardized incidence ratios (SIR) with 95% confidence intervals (CI). Patients, followed for an average of 21 years, were at a higher overall risk of cancer. Some 26 cancer diagnoses, after excluding multiple diagnoses of nonmelanoma skin cancer in one man, produced an overall SIR of 3.2 (95% CI 2.1-4.6). We found statistically significantly increased risks for kidney, thyroid, endocrine, lymphoma and nonmelanoma skin cancer. There was no modification of cancer risk among parents and siblings, with an average of 21 years of follow-up. This study did not identify a heterozygote advantage for CF gene mutations in relation to cancer risk.
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| 32. |
- Johannesson, Marie, et al.
(författare)
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Lung function changes in relation to menstrual cycle in females with cystic fibrosis
- 2000
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 94:11, s. 1043-1046
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Tidskriftsartikel (refereegranskat)abstract
- Oestrogen and progesterone have been shown to have impact on cystic fibrosis transmembrane conductance regulator (CFTR) gene expression, tone of smooth muscle in the airways, immune response, exhaled nitric oxide and cytology in the tracheobronchial epithelium. The aim of this investigation was to study the influence of menstrual cyclicity on airway symptoms among cystic fibrosis (CF) females. Twelve CF women (mean age 30 years, mean Shwachman score 85) kept daily records during three menstrual cycles of lung function, sputum quality and need for intravenous antibiotics. Paired t-test was used as a statistical method to compare the airway symptoms between the time of ovulation (high levels of oestrogen and low levels of progesterone), the luteal phase (high levels of oestrogen and progesterone) and menstruation (low levels of oestrogens and progesterone). Forced expiratory volume in 1 sec (FEV1) was significantly higher during the luteal phase (66% of predicted) compared to during ovulation (63%) and menstruation (61%) (P<0.01). Forced vital capacity (FVC) showed the same pattern, being significantly higher during the luteal phase compared with during menstruation (mean 75% vs. 70%, P<0.01). In conclusion, lung function changes were found during menstrual cycles in women with cystic fibrosis. These changes are probably related to changes in progesterone levels during the menstrual cycles. This result warrants further studies to understand the complexity of CF lung disease in women.
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| 33. |
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| 34. |
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| 35. |
- Johannesson, Susanne, 1960-, et al.
(författare)
-
Training in Gerontology - what is it good for?
- 2010
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Konferensbidrag (refereegranskat)abstract
- One of the challenges for all universities is to implement theoretical knowledge and research into practice. Gerontology is multidisciplinary and many professionals may benefit from training in Gerontology. At the Institute of Gerontology, School of Health Sciences, Jönköping University, students are offered different courses in Gerontology from basic to advanced level and up to doctoral program. The question is how they use the gained knowledge in Gerontology. Theoretically, many different professions can use training in Gerontology to develop care, rehabilitation, and social services for elderly people but do they, in practice? To use education in Gerontology there are several factors that must be in accordance, such as working load, resources, openness, and flexibility in the working environment and more. This study has investigated how Gerontology students have used their gained knowledge in practice and if the increased knowledge contributed to improved care and services for elderly people. Furthermore, the aim was also to find out which factors that encouraged versus prevented the students to use their new knowledge in gerontology. A questionnaire was sent to all students with 7,5 or more ECTS in Gerontology at advanced level – in total 255 persons – in September 2009. In December 2009, 101 students had filled out and returned the questionnaire. The students who answered the questionnaire had on average 60 ECTS in Gerontology at advanced levels. This presentation will introduce the results from this study about the use of higher education in Gerontology in practice.
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| 36. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
-
Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 37. |
- Knudsen, Per Kristian, et al.
(författare)
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Differences in prevalence and treatment of Pseudomonas aeruginosa in cystic fibrosis centres in Denmark, Norway and Sweden
- 2009
-
Ingår i: Journal of Cystic Fibrosis. - : Elsevier BV. - 1569-1993 .- 1873-5010. ; 8:2, s. 135-142
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic Pseudomonas aeruginosa (PA) infection causes increased morbidity and mortality in cystic fibrosis (CF). This study aimed to answer the following questions: Does the prevalence of chronic infection with PA differ between the CF centres in Scandinavia? Which differences exist concerning segregation and treatment of PA? METHODS: 989 patients (86%) from all eight CF-centres in Scandinavia were included. Demographic and clinical data, including PA colonisation status based on cultures and serology, were recorded at inclusion. The patients were followed prospectively for 1 year, recording number of days with anti-PA antibiotic treatment. RESULTS: In all pancreatic insufficient (PI) patients (n=890) the prevalence of chronic PA infection at each centre ranged from 25.8% to 48.9%, but were not significantly different. In PI patients <19 years the prevalence was 14.5% in Copenhagen compared to 30.9% in the Swedish centres pooled (p=0.001). In intermittently colonised PI patients <19 years the median number of days per year on anti-PA antibiotics was almost 6 times higher in Copenhagen (mean 86 (110), median 61 days) compared to the Swedish centres pooled (mean 27 (52), median 11 days) (p=0.037). The pulmonary function was similar. CONCLUSIONS: It is possible to maintain a very low prevalence of chronic PA infection in CF patients <19 years. We speculate that this was most likely due to a very intensive treatment of intermittently colonised patients with inhaled anti-PA antibiotics over prolonged periods of time in some centres. Since lung function was similar in centres with less intensive use of inhaled antibiotics, studies comparing different treatment modalities and other parts of CF care are needed to define the best clinical practice, including how to use antibiotics in the most rational way.
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| 38. |
- Kollberg, Hans, et al.
(författare)
-
Oral administration of specific yolk antibodies (IgY) may prevent Pseudomonas aeruginosa infections in patients with cystic fibrosis : a phase I feasibility study
- 2003
-
Ingår i: Pediatric Pulmonology. - : Wiley. - 8755-6863 .- 1099-0496. ; 35:6, s. 433-40
-
Tidskriftsartikel (refereegranskat)abstract
- Respiratory infection is the major cause of morbidity and mortality in cystic fibrosis (CF) patients. Chronic Pseudomonas aeruginosa (PA) infections ultimately occur in virtually all patients. It is impossible to eradicate PA when a patient has been chronically colonized. Immunotherapy with specific egg-yolk antibodies (IgY) may be an alternative to antibiotics for the prevention of PA infections. We wanted to determine if treatment with specific IgY can prolong the period between the first and the second PA colonization? And long-term, can the treatment diminish the number of positive PA cultures and postpone the onset of chronic colonization? CF patients gargled daily with an IgY-antibody preparation, purified from eggs of hens immunized with PA bacteria. They were compared to a group of patients who did not gargle with the preparation. Both groups had their first colonization with PA eradicated by antibiotics. The basic treatment was essentially the same in both groups. In the initial study, the period between the first and second colonization with PA was significantly prolonged for the treated vs. the control group (Kaplan-Meier P = 0.015, Breslow test). In the prolonged study, the treated group had only 2.5 sputum cultures positive for PA per 100 months of observation, and none of these patients became chronically colonized with PA. No adverse events were reported. In the control group, 13.7 cultures per 100 months of observation were positive for PA, and 5 (24%) patients became chronically colonized with PA. This feasibility study shows that antipseudomonal IgY has the potential to effectively prevent PA colonization without any severe adverse effects. A phase III study should be initiated.
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| 39. |
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| 40. |
- Le Pennec, Guénolé, et al.
(författare)
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Adaptation to dislodgement risk on wave-swept rocky shores in the snail Littorina saxatilis.
- 2017
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 12:10
-
Tidskriftsartikel (refereegranskat)abstract
- The periwinkle Littorina saxatilis has repeatedly evolved both a small, fragile and globose "wave ecotype" confined to wave-swept shores and a large, robust and elongated "crab ecotype" found in nearby crab-rich but less-exposed shores. This phenotypic divergence is assumed to reflect, in some part, local adaptation to wave exposure, but this hypothesis has received incomplete experimental testing. Here, we report a test of the prediction that the wave ecotype has a higher capacity to resist water flow than the crab ecotype. We sampled snails along a crab-wave transect and measured their resistance to dislodgement in a high-speed water flume with water speeds that match those of breaking waves in a range of relevant field conditions. Snails from the wave environment were consistently more resistant to water flow than snails from the crab environment and high resistance was positively correlated with the surface area of the foot and the area of the outer aperture contour both relative to shell size, and to the extent of lateral shell compression. In a separate experiment, we found that snails raised in still water in a common garden showed higher resistance to water flow if originating from a wave environment than from a crab environment, and this was true both at juvenile (2 weeks) and adult (10 months) developmental stages. This result suggests genetic control of a distinct "wave adapted" phenotype, likely to be maintained under strong divergent selection between the two adjacent habitats.
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| 41. |
- Lee, Stephanie, et al.
(författare)
-
Patients' willingness to pay for autologous blood donation
- 1997
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Ingår i: Health policy (Amsterdam). - : Elsevier Ireland Ltd. - 1872-6054 .- 0168-8510. ; 40:1, s. 1-12
-
Tidskriftsartikel (refereegranskat)abstract
- Most cost-effectiveness analyses of autologous blood donation show very small health benefits for a substantial increase in resource utilization. However, these analyses do not consider the psychological benefits of peace of mind to patients participating in the program. In order to quantitate these benefits, we employed contingent valuation methodology to measure the willingness of patients undergoing elective surgery, to pay for autologous blood donation. The internal consistency of patient responses was investigated through correlations of willingness-to-pay values with risk perceptions and patient characteristics. Two hundred and thirty-five patients completed the self-administered questionnaire which included demographic, willingness-to-pay and risk perception questions. Median population willingness to pay for autologous blood donation was approximately $900 per patient. In multivariate analysis, willingness to pay varied significantly with dread of allogenic transfusion, perceived risk of requiring a blood transfusion and income. Patients who participate in autologous blood donation programs value the procedure highly and state they are willing to pay significant amounts out of pocket to assure themselves of available autologous blood. Willingness to pay correlated significantly with factors expected to influence value decisions.
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| 42. |
- Lee, Samuel, et al.
(författare)
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Perceptions and preferences of autologous blood donors
- 1998
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Ingår i: Transfusion (Philadelphia, Pa.). - : Blackwell Publishing. - 1537-2995 .- 0041-1132. ; 38:8, s. 757-763
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The public's perception of autologous blood donation and transfusion as a worthwhile alternative to allogeneic blood transfusion increased dramatically with discovery of the human immunodeficiency virus. However, new concerns are being raised about the health outcomes and cost-effectiveness of the procedure. As more restrictive guidelines for autologous blood donation evolve, opposition from patients concerned about exposure to allogeneic blood may arise. Physicians' ability to reassure patients and garner their support for more restrictive policies requires an understanding of patients' concerns. The motivations, perceptions, and preferences of patients currently participating in autologous blood donation programs were investigated in this study. STUDY DESIGN AND METHODS: Results from two questionnaire studies of 647 autologous blood donors are presented. The questionnaires assessed demographics, risk perceptions, preferences, willingness to pay, and reactions to different interventions designed to decrease patient preference for autologous blood donation. RESULTS: Patients expressed a strong preference for the availability of autologous blood and indicated that they would be willing to pay substantial amounts of money even ii the procedure were not covered by insurance. Despite education about the low risks of complications from allogeneic transfusions, an aversion to allogeneic transfusion and a willingness to pay for autologous blood donation persisted. Patients were not reassured by information on better infectious disease testing or physician recommendation against autologous blood donation. CONCLUSION: Patients currently participating in autologous blood donor programs strongly prefer continued access to this procedure, primarily because they remain concerned about the complications of allogeneic transfusions. They may not be significantly reassured despite increasingly rigorous and costly improvements in donor and component screening.
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| 43. |
- Nilsson, Doris, 1952-, et al.
(författare)
-
Evaluation of the Swedish Trauma Symptom Inventory-2 in a clinical and a student population
- 2018
-
Ingår i: European Journal of Trauma & Dissociation. - : Elsevier BV. - 2468-7499. ; 2:2, s. 71-82
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction The Trauma Symptom Inventory-2 (TSI-2) is a broad-spectrum assessment instrument designed to identify symptoms that can appear in the aftermath of potentially traumatic experiences.Objective This study aimed to evaluate the external and internal validity of this newly reconstructed instrument.Method In total, 696 individuals participated in the study, including 83 psychiatric outpatients. Participants answered the TSI-2, together with a trauma history questionnaire, and other questionnaires assumed to correlate with the different scales included in the TSI-2.Results Validity was evaluated by correlations between the TSI-2 and the other instruments and by the differences between clinical and non-clinical populations. Reliability was calculated by testing internal consistency and test-re-test reliability. A confirmatory factor analysis (CFA) was computed to test the postulated four-factor structure. Cronbach's alpha was found to be good and ranged from α = .77 to .91 and test-retest reliability was strong. Strong to satisfactory correlations were found between the TSI-2 and the other instruments. The student sample scored significantly lower than the clinical group on all clinical scales. Sensitivity and specificity were calculated with different cut-off scores.Conclusion Despite the CFA demonstrating a questionably good model of fit, most of the scales proved to be sound and the TSI-2 could be recommended as a broad-spectrum assessment instrument.
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| 44. |
- Nilsson, Doris, et al.
(författare)
-
Trauma Symptom Inventory™ -2 TSI-2 : Svensk Version
- 2015
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- TSI-2 är ett självrapporteringsformulär som mäter posttraumatisk stress och relaterade symptom och beteenden. TSI-2 syftar till att identifiera symptom som kvarstår hos individen efter en eller flera svåra livshändelser. Mer specifikt är instrumentet avsett att användas för vuxna som har upplevt traumatiska händelser i livet såsom exempelvis fysiska eller sexuella övergrepp, olyckor, katastrofhändelser, traumatiska förluster, dödsfall av närstående, medicinska trauman eller bevittnat hot och våld. TSI-2 mäter ett brett spektrum av traumatiska symptom och lämpar sig framförallt för screening men kan också användas för att utvärdera effekter av psykoterapeutiska interventioner.TSI-2 består av 136 påståenden som ger resultat på:Två validitetsskalorUnderrapportering eller förnekande av symptom, samt en skala gällande överrapportering av traumarelaterade symptom.Fyra faktorerSjälvförvirring, Posttraumatisk stress, Externalisering och Somatisering.Tolv kliniska skalorÅngestfylld spändhet, Depression, Ilska, Invaderande återupplevande, Undvikande, Dissociation, Somatisk upptagenhet, Sexuella svårigheter, Självmordsbenägenhet, Osäker anknytning, Skadad självkänsla, Spänningsreducerande beteende.Den svenska versionen av TSI-2 är standardiserad och normerad vid Linköpings universitet och Uppsala universitet under åren 2012-2014. Normgruppen består av sammanlagt 693 individer i åldrarna 18-65 år. En klinisk grupp med 83 individer ingår också i valideringen av den svenska versionen av TSI-2. Utvecklingsarbetet och den svenska versionens psykometriska egenskaper beskrivs i manualen, som även innehåller anvisningar för administrering, poängsättning och tolkning samt köns- och åldersspecifika normtabeller.
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| 45. |
- Nilsson, Elin, et al.
(författare)
-
More than 10 years' continuous oral treatment with specific immunoglobulin Y for the prevention of Pseudomonas aeruginosa infections : a case report
- 2007
-
Ingår i: Journal of Medicinal Food. - : Mary Ann Liebert Inc. - 1096-620X .- 1557-7600. ; 10:2, s. 375-378
-
Tidskriftsartikel (refereegranskat)abstract
- Immunotherapy with specific antibodies is an alternative to antibiotics for the prevention of infections in humans and animals. We have used orally administered immunoglobulin Y (IgY) preparations, purified from eggs of hens immunized with Pseudomonas aeruginosa bacteria, to prevent pulmonary P. aeruginosa infections in a group of patients with cystic fibrosis (CF). Respiratory infections are major problems for CF patients because of the thick mucus in the airways, and chronic P. aeruginosa lung infections occur in virtually all CF patients and cause morbidity and mortality. The IgY-treated group had only 2.5 P. aeruginosa-positive sputum cultures per 100 months, and none of the IgY-treated patients became chronically colonized with P. aeruginosa. In the control group, 13.7 of the cultures per 100 months were positive for P. aeruginosa, and 24% of patients became chronically colonized with P. aeruginosa. The first enrolled patient in this study has now been treated continuously for more than 10 years. During the first 8 years she only had four P. aeruginosa-positive cultures. After 8 years she became chronically infected, but still after 10 years the bacteria have not turned mucoid. No negative side effects of IgY treatment have been noted during these 10 years. To our knowledge this is the longest treatment with specific yolk antibodies for therapeutic purposes.
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| 46. |
- Nilsson, Harriet, et al.
(författare)
-
CFTR and tight junctions in cultured bronchial epithelial cells
- 2010
-
Ingår i: Experimental and molecular pathology (Print). - : Elsevier BV. - 0014-4800 .- 1096-0945. ; 88:1, s. 118-127
-
Tidskriftsartikel (refereegranskat)abstract
- Airway epithelial salt and water transport takes place through paracellular and transcellular pathways. This transport depends critically on the epithelial sodium channel (ENaC) and the cystic fibrosis transmembrane conductance regulator (CFTR), operating in concert with the paracellular pathway through the tight junctions (TJs). Normal (16HBE14o-), cystic fibrosis (CFBE41o-), and corrected CFBE41o- (CFBE41o pCep4) airway epithelial cell lines were cultured under isotonic conditions. Transepithelial electrical resistance (TEER) was measured as indicator of the tightness of the cultures. Morphology was investigated by immunofluorescence and paracellular permeability by lanthanum nitrate or [14C] mannitol as permeability markers. CFBE41o pCep4 cells developed lower TEER than CFBE41o- cells. Addition of a specific inhibitor of CFTR (CFTRinh-172) to 16HBE14o- and CFBE pCep4 cells resulted in a time-dependent increase in TEER whereas stimulation of CFTR by IBMX and forskolin caused a decrease. Permeability to lanthanum and [14C] mannitol was lower in 16HBE14o- cells exposed to CFTRinh-172 and in CFBE41o- cells compared to untreated 16HBE14o- and CFBE41o pCep4 cells, respectively. 16HBE14o- cells exposed to IBMX and forskolin showed higher permeability to lanthanum but lower permeability to [14C] mannitol compared to control. Immunofluorescence revealed a disorganisation of F-actin and a-tubulin in 16HBE14o- cells exposed to CFTRinh-172, which was not seen in untreated cultures. A higher degree of disorganised F-actin and a-tubulin was also seen in CFBE41o- cells compared to CFBE41o- pCep4 cells. Changes in F-actin and a-tubulin in 16HBE14o- cells exposed to IBMX and forskolin were also seen, although these were less apparent. These results suggest the possibility of an interaction between the activity of CFTR and the TJ protein complex, probably via the cytoskeleton.
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| 47. |
- Nilsson, Harriet, et al.
(författare)
-
Effects of hyperosmotic stress on cultured airway epithelial cells
- 2007
-
Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 330:2, s. 257-269
-
Tidskriftsartikel (refereegranskat)abstract
- Inhalation of hyperosmotic solutions (salt, mannitol) has been used in the treatment of patients with cystic fibrosis or asthma, but the mechanism behind the effect of hyperosmotic solutions is unclear. The relation between osmolarity and permeability changes was examined in an airway cell line by the addition of NaCl, NaBr, LiCl, mannitol, or xylitol (295–700 mOsm). Transepithelial resistance was measured as an indicator of the tightness of the cultures. Cell-cell contacts and morphology were investigated by immunofluorescence and by transmission electron microscopy, with lanthanum nitrate added to the luminal side of the epithelium to investigate tight junction permeability. The electrolyte solutions caused a significant decrease in transepithelial resistance from 450 mOsm upwards, when the hyperosmolar exposure was gradually increased from 295 to 700 mOsm; whereas the nonelectrolyte solutions caused a decrease in transepithelial resistance from 700 mOsm upwards. Old cultures reacted in a more rigid way compared to young cultures. Immuno-fluorescence pictures showed weaker staining for the proteins ZO-1, claudin-4, and plakoglobin in treated samples compared to the control. The ultrastructure revealed an increased number of open tight junctions as well as a disturbed morphology with increasing osmolarity, and electrolyte solutions opened a larger proportion of tight junctions than nonelectrolyte solutions. This study shows that hyperosmotic solutions cause the opening of tight junctions, which may increase the permeability of the paracellular pathway and result in increased transepithelial water transport.
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| 48. |
- Nilsson, Harriet
(författare)
-
Studies of Tight Junctions and Airway Surface Liquid in Airway Epithelium with Relevance to Cystic Fibrosis
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cystic fibrosis (CF) is a multi-organ autosomal recessive disease of fluid-transporting epithelia, due to a mutation in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR is a cAMP-regulated Cl-channel involved in various regulatory processes. Salt and water transport depend on CFTR and the epithelial sodium channel (ENaC), operating in concert with the paracellular pathway through the tight junctions (TJ). The ionic composition of the ASL has been assumed to be altered in CF, resulting in a fatal accumulation of viscous mucus in the airways. ASL samples were collected from tracheal and nasal fluid in normal and transgenic CF mice and from the fluid covering the apical surface of normal bronchial cells (16HBE14o-) and a CF human bronchial cell line (CFBE41o-). Analysis of the elemental content of the ASL was performed by X-ray microanalysis. The ASL contained more Na and Cl in CFTR-deficient or DF508-CFTR-containing cells than in control cells with wild- type CFTR. The relation between osmolarity and TJ permeability was examined by the addition of salt or sugar (295-700 mOsm) to 16HBE14o- cells, where the integrity of TJ was evaluated by transepithelial electrical resistance (TEER) measurements. Studies of interaction between the activity of CFTR, TJ and cytoskeleton were performed in CFBE41o-, plasmid corrected CFBE41o- (CFBE41o pCep4), and 16HBE14o- cells exposed to an inhibitor of CFTR (CFTRinh-172). The TJ were investigated by determining the paracellular permeability to lanthanum ions or with [14C] mannitol. Cytoskeletal changes were evaluated by immunofluorescence. Hyperosmotic stress resulted in opening of TJ. Inhalation of hypertonic salt or sugar solutions may open TJ, leading to enhanced paracellular water transport and increased ASL volume, diluted mucus and enhanced mucociliary clearance. This may explain the beneficial effect of this treatment for CF-patients. In healthy airway epithelial cells, inhibition of CFTR by CFTRinh-172 resulted in an increased TEER, whereas stimulation of CFTR by IBMX/forskolin caused a decrease. The paracellular permeability was inversely proportional to TEER. Immunofluorescence revealed a disorganization of cytoskeletal proteins in CF-cells. These results point toward a possible interaction between the activity of CFTR and TJ protein complex, presumably via the cytoskeleton.
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| 49. |
- Olesen, Hanne Vebert, et al.
(författare)
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Gender differences in the Scandinavian cystic fibrosis population.
- 2010
-
Ingår i: Pediatric pulmonology. - : Wiley. - 1099-0496 .- 8755-6863. ; 45:10, s. 959-65
-
Tidskriftsartikel (refereegranskat)abstract
- To explore whether gender differences in the Scandinavian Cystic Fibrosis (CF) patients exist in the areas of key clinical parameters, complications, and medication.
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| 50. |
- Oliynyk, Igor
(författare)
-
Advances in Pharmacological Treatment of Cystic Fibrosis
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cystic fibrosis (CF) is an inborn, hereditary disease, due to mutations in the gene for a cAMP-activated chloride (Cl-) channel, the cystic fibrosis transmembrane conductance regulator (CFTR). As a result of impaired ion and water transport,the airway mucus is abnormally viscous, which leads to bacterial colonization.Recurrent infections and inflammation result in obstructive pulmonary disease.Similar changes in the pancreas lead to pancreatic insufficiency.Several compounds have been tested to improve transepithelial ion transport in CF patients, either via activation of the mutant CFTR, or via stimulation of alternative chloride channels. The main purpose of this thesis was to find substances that might correct the defective ion transport in epithelial cells in CFand could be useful for the pharmacological treatment of CF patients. Long-term treatment with the macrolide antibiotic azithromycin (AZM)improved clinical parameters and lung function in CF patients and increased Cl- transport in CF bronchial epithelial cells (CFBE) (Paper I); although mRNA expression of the CFTR gene remained unchanged.In contrast, pre-exposure to the mucolytic antioxidant N-acetylcysteine (NAC) increased CFTR protein expression and was associated with increased Cl- efflux from CFBE cells (Paper II). Clinical trials of this substance might be warranted. Duramycin has been the subject of clinical trials that finished in June2009. Up till now, no results from this study are available. The effect of this substance on Cl- efflux from three CF and three non-CF cell lines (Paper III) was disappointing. An effect was found only in CFBE cells, the effect was minimal, occurred in a narrow concentration range, and was not associated with an increase in the intracellular calcium concentration [Ca2+]i. The fact that NO-donors stimulated Cl- efflux from CFBE cells (but did notchange [Ca2+]i) after several hours of preincubation suggests that these substances may be a potentially interesting group of compounds for the treatment of CF (Paper IV). A model for the effect of NO-donors on Cl- efflux is presented.
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