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- Filiou, A, et al.
(författare)
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Development of Sensitization to Multiple Allergen Molecules from Preschool to School Age Is Related to Asthma
- 2022
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 183:6, s. 628-639
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> Allergic sensitization in early life has been identified as a strong risk factor for subsequent asthma in childhood. It is still unclear why only a part of sensitized children develop asthma, and the role of specific allergen molecules in asthma pathogenesis is ambiguous [<i>Pharmacol Ther</i>. 2009 Feb;121(2):174–84]. We assessed the sensitization to multiple allergen molecules longitudinally and explored its relation to persistent asthma at 7 years. <b><i>Methods:</i></b> Seventy-two children included during an acute wheezing episode (cases) were followed prospectively from early preschool age (EPA) to age 7, and compared to 43 healthy controls at EPA. Allergen molecules were analyzed at EPA and age 7 using ImmunoCAP Solid-phase Allergen Chip (ISAC). Asthma diagnosis at 7 years was based on symptoms, medication, and spirometry. <b><i>Results:</i></b> At EPA, cases compared to controls showed a tendency toward having a higher prevalence of allergic sensitization (23.6% vs. 9.3%, <i>p</i> = 0.055). The prevalence of sensitization increased in cases from EPA to 7 years (23.6% vs. 38.9%; <i>p</i> = 0.048) as well as the median number (range) of immunoglobulin E (IgE)-reactive molecules 3 (3–14) versus 6.5 (1–21); <i>p</i> = 0.024. Sensitization to each additional molecule from EPA to the age of 7 was significantly related to asthma at 7 (OR = 1.25, 95% confidence interval [1.01, 1.54]). <b><i>Conclusion:</i></b> Polysensitization, assessed by allergen molecules, had a significant impact on persistent asthma at school age. The extent of sensitization, illustrated by molecular spreading from preschool to school age, was related to asthma diagnosis at 7 years in children with a history of wheezing at early life.
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- Eierhoff, T., et al.
(författare)
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A lipid zipper triggers bacterial invasion
- 2014
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 111:35, s. 12895-12900
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Tidskriftsartikel (refereegranskat)abstract
- Glycosphingolipids are important structural constituents of cellular membranes. They are involved in the formation of nanodomains ("lipid rafts"), which serve as important signaling platforms. Invasive bacterial pathogens exploit these signaling domains to trigger actin polymerization for the bending of the plasma membrane and the engulfment of the bacterium-a key process in bacterial uptake. However, it is unknown whether glycosphingolipids directly take part in the membrane invagination process. Here, we demonstrate that a "lipid zipper," which is formed by the interaction between the bacterial surface lectin LecA and its cellular receptor, the glycosphingolipid Gb3, triggers plasma membrane bending during host cell invasion of the bacterium Pseudomonas aeruginosa. In vitro experiments with Gb3-containing giant unilamellar vesicles revealed that LecA/Gb3-mediated lipid zippering was sufficient to achieve complete membrane engulfment of the bacterium. In addition, theoretical modeling elucidated that the adhesion energy of the LecA-Gb3 interaction is adequate to drive the engulfment process. In cellulo experiments demonstrated that inhibition of the LecA/Gb3 lipid zipper by either lecA knockout, Gb3 depletion, or application of soluble sugars that interfere with LecA binding to Gb3 significantly lowered P. aeruginosa uptake by host cells. Of note, membrane engulfment of P. aeruginosa occurred independently of actin polymerization, thus corroborating that lipid zippering alone is sufficient for this crucial first step of bacterial host-cell entry. Our study sheds new light on the impact of glycosphingolipids in the cellular invasion of bacterial pathogens and provides a mechanistic explication of the initial uptake processes.
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- Finizia, Caterina, 1961, et al.
(författare)
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Advanced laryngeal cancer T3-T4 in Sweden: a retrospective study 1986-1990. Survival and locoregional control related to treatment.
- 1996
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Ingår i: Acta oto-laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 116:6, s. 906-12
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Tidskriftsartikel (refereegranskat)abstract
- Different treatment modalities for advanced laryngeal cancer are much discussed in the literature. One-hundred-and-sixty patients with T3-4, N0-3, M0-1 laryngeal cancer diagnosed in Sweden between 1986 and 1990 were retrospectively analysed. One hundred (65 T3: 35 T4) received radical radiotherapy with salvage surgery (RRSS) in case of residual or recurrent disease. Thirty-eight (11T3: 27 T4) patients received surgery with or without radiotherapy (S +/- RT). Twenty-two patients received no treatment. After a median follow up of 4.4 years, the estimated 5-year actuarial corrected survival and 3-year locoregional control were 59% and 44% for T3 RRSS and 47% and 54% for T3 S +/- RT. No significant difference between the different treatment modalities was found. The 5-year corrected survival rate and the locoregional control at 3 years between T4-RRSS (32%; 26%) and T4-S + RT (58%; 68%) groups were significantly different (p < 0.05 and p < 0.01). This might suggest that surgery with or without radiotherapy still has its place as a treatment modality for patients with advanced T4 laryngeal carcinoma.
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- Logroscino, G, et al.
(författare)
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Incidence of Syndromes Associated With Frontotemporal Lobar Degeneration in 9 European Countries
- 2023
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 80:3, s. 279-286
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Tidskriftsartikel (refereegranskat)abstract
- Diagnostic incidence data for syndromes associated with frontotemporal lobar degeneration (FTLD) in multinational studies are urgent in light of upcoming therapeutic approaches.ObjectiveTo assess the incidence of FTLD across Europe.Design, Setting, and ParticipantsThe Frontotemporal Dementia Incidence European Research Study (FRONTIERS) was a retrospective cohort study conducted from June 1, 2018, to May 31, 2019, using a population-based registry from 13 tertiary FTLD research clinics from the UK, the Netherlands, Finland, Sweden, Spain, Bulgaria, Serbia, Germany, and Italy and including all new FTLD-associated cases during the study period, with a combined catchment population of 11 023 643 person-years. Included patients fulfilled criteria for the behavioral variant of frontotemporal dementia (BVFTD), the nonfluent variant or semantic variant of primary progressive aphasia (PPA), unspecified PPA, progressive supranuclear palsy, corticobasal syndrome, or frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS). Data were analyzed from July 19 to December 7, 2021.Main Outcomes and MeasuresRandom-intercept Poisson models were used to obtain estimates of the European FTLD incidence rate accounting for geographic heterogeneity.ResultsBased on 267 identified cases (mean [SD] patient age, 66.70 [9.02] years; 156 males [58.43%]), the estimated annual incidence rate for FTLD in Europe was 2.36 cases per 100 000 person-years (95% CI, 1.59-3.51 cases per 100 000 person-years). There was a progressive increase in FTLD incidence across age, reaching its peak at the age of 71 years, with 13.09 cases per 100 000 person-years (95% CI, 8.46-18.93 cases per 100 000 person-years) among men and 7.88 cases per 100 000 person-years (95% CI, 5.39-11.60 cases per 100 000 person-years) among women. Overall, the incidence was higher among men (2.84 cases per 100 000 person-years; 95% CI, 1.88-4.27 cases per 100 000 person-years) than among women (1.91 cases per 100 000 person-years; 95% CI, 1.26-2.91 cases per 100 000 person-years). BVFTD was the most common phenotype (107 cases [40.07%]), followed by PPA (76 [28.46%]) and extrapyramidal phenotypes (69 [25.84%]). FTD-ALS was the rarest phenotype (15 cases [5.62%]). A total of 95 patients with FTLD (35.58%) had a family history of dementia. The estimated number of new FTLD cases per year in Europe was 12 057.Conclusions and RelevanceThe findings suggest that FTLD-associated syndromes are more common than previously recognized, and diagnosis should be considered at any age. Improved knowledge of FTLD incidence may contribute to appropriate health and social care planning and in the design of future clinical trials.
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