| 11. |
- Alenmyr, Lisa, et al.
(författare)
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TRPV4-mediated calcium influx and ciliary activity in human native airway epithelial cells.
- 2014
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843 .- 1742-7835. ; 114:2, s. 210-216
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Tidskriftsartikel (refereegranskat)abstract
- The transient receptor potential, vanilloid 4 (TRPV4), is a calcium permeable ion channel expressed in airway epithelial cells. Based on studies of cell lines and animals, TRPV4 has been suggested to play a role in the regulation of ciliary beat frequency (CBF). Whether the same is true for human ciliated epithelial cells is not known. Therefore, the aim was to examine the expression and function of TRPV4 in human native nasal epithelial cells. Expression of TRPV4 mRNA in nasal epithelial cells and in the cell lines BEAS2B and 16HBE was confirmed by quantitative real-time PCR. A marked apical TRPV4 immunoreactivity was observed in nasal epithelial cells using immunocytochemistry. Responses to pharmacological modulation of TRPV4 were assessed with calcium imaging and CBF measurements. The TRPV4 agonist GSK1016790A produced concentration-dependent calcium responses in TRPV4-expressing HEK293, BEAS2B and 16HBE cells, and the TRPV4 antagonist HC067047 caused a rightward shift of the GSK1016790A concentration-response curves. Nasal epithelial cells responded to the TRPV4 agonist GSK1016790A with increased intracellular calcium signals and increased CBF, followed by cessation of ciliary beating and cell death. These effects were prevented or inhibited by the TRPV4 antagonist HC067047, the TRP channel blocker ruthenium red or removal of extracellular calcium. We conclude that TRPV4 is expressed in human primary nasal epithelial cells and modulates epithelial calcium levels and CBF. Thus, TRPV4 may participate in mucociliary clearance and airway protection. However, exaggerated activation of TRPV4 may result in epithelial cell death. This article is protected by copyright. All rights reserved.
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| 12. |
- Altunbulakli, Can, et al.
(författare)
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Targeted spatial proteomic analysis of CD8+ T- and myeloid cells in tonsillar cancer
- 2023
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Ingår i: Frontiers in Oncology. - 2234-943X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tonsillar cancer is caused by high-risk human papillomavirus (HPV), tobacco smoking, and alcohol abuse. Aspects of the patient’s immune response to this disease have arisen as prognostic factors and treatment targets, reflecting differences in the type and protein expression profile of immune cells. Because tonsillar cancers are heterogenous lesions such data need to be spatially resolved. Methods: In this study, we aim to explore inter-patient and intra-tumoral sources of variation in tonsillar cancer using immunofluorescence and targeted spatial proteomics to interrogate a cohort of 105 patients. Furthermore, we assess prognostic factors and elucidate molecular targets. We have used CD8, CD11c, and Pan-cytokeratin (PanCK) to quantify and locate immune cells driving antigen-specific cellular immunity. Guided by immunofluorescence information, we selected 355 CD8+, CD11c+, or PanCK+ areas inside and outside (i.e., stroma) cancer-cell islets, to quantify 43 immune-related proteins using digital spatial profiling. Results: Quantitative analysis of immunofluorescence in combination with clinical data revealed that the abundance of total CD8+ cells and CD8+ cells infiltrating cancer-cell islets, respectively, were associated with higher 5-year disease-free survival and overall survival, independently of HPV-status and clinical stage. Comparison of CD8+ cells inside and outside cancer-cell islets revealed an upregulation of effector CD8+ T-cell and immune checkpoint molecules in the former. Among these, the expression of PD-L1 by CD8+ T-cells was associated with lower all-cause mortality in a univariate proportional hazards model. Similarly, a comparison of tumor boundary and stroma CD11c+ cells showed upregulation of both co-stimulatory and immune checkpoint molecules with proximity to tumor cell islets. Conclusion: Our findings highlight the relevance of analyzing aspects of tumor micro-architecture in the search of prognostic markers and molecular targets for tonsillar cancer. The abundance of intra-tumoral CD8+ T-cells can be considered a positive predictive marker for tonsillar cancer, while the significance of PD-L1 expression by intra-tumoral CD8+ T-cells warrants further evaluation. Location-based differences in CD8+ and CD11c+ cells suggest an immune cell-altering effect on the tumor microenvironment, and grant new insight into which cells that can be targeted by novel therapeutic agents.
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| 13. |
- Andersson, Morgan, et al.
(författare)
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Barrier-enforcing measures as treatment principle in allergic rhinitis: a systematic review
- 2014
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Ingår i: Current Medical Research and Opinion. - : Informa Healthcare. - 1473-4877 .- 0300-7995. ; 30:6, s. 1131-1137
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Forskningsöversikt (refereegranskat)abstract
- Background and objectives Barrier-enforcing measures have been suggested as treatment options for allergic rhinitis. This review identifies and describes the literature on the subject. Methods Relevant publications were searched for in the PubMed database (search entries: 'allergic rhinitis' and 'treatment'). The evaluation comprised condition (seasonal or perennial allergic rhinitis), type of intervention, duration of treatment, study design, peer review status or not, number of test subjects, type of allergen exposure, and outcome in terms of effects or not on nasal symptoms of allergic rhinitis. Results Fifteen studies were either identified in the PubMed database search or from the reference lists of identified publications. Seven were placebo-controlled, randomized, and peer-reviewed, and symptom-reducing effects were reported by all of these reports. Limitations of this review reflect that the remainder of the studies had inferior designs, particularly lack of placebo control. Conclusions Barrier-enforcing measures as achieved by nasal administrations of cellulose powder and microemulsions, respectively, have symptom-reducing effects in allergic rhinitis.
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| 14. |
- Andersson, Morgan, et al.
(författare)
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Effects of a topical microemulsion in house dust mite allergic rhinitis.
- 2011
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843 .- 1742-7835. ; 108:2, s. 146-148
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Tidskriftsartikel (refereegranskat)abstract
- We have previously demonstrated that a topical microemulsion can attenuate symptoms and signs of seasonal allergic rhinitis. This likely reflects that the microemulsion interferes with the interaction between the allergen and the mucosa. Whether or not the finding translates to conditions caused by other inhaled agents such as house dust mite allergen is unknown. Patients with perennial allergic rhinitis caused by house dust mite were subjected to topical microemulsion treatment in a randomized, double-blinded and crossover design with isotonic saline as control. Morning symptoms were monitored, change from baseline was assessed and the treatments were compared. On the first days of the isotonic saline and microemulsion runs, before any treatment was given, total nasal symptoms were scored to 2.8 and 3.1 (range 0-9), respectively. Nasal symptoms were reduced by intervention with the microemulsion: the change from baseline was consistent for the microemulsion and the difference between the microemulsion and isotonic saline reached statistical significance in favour of the former. We conclude that intervention with a microemulsion may reduce symptoms of house dust mite allergic rhinitis at natural allergen exposure. Our findings suggest the possibility that topical microemulsions can be a useful option to reduce nasal mucosal exposure to allergen in perennial allergic rhinitis..
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| 15. |
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| 16. |
- Andersson, Morgan, et al.
(författare)
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Nasal treatment with a microemulsion reduces allergen challenge-induced symptoms and signs of allergic rhinitis
- 2008
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 128:6, s. 666-669
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Tidskriftsartikel (refereegranskat)abstract
- Conclusions. Intranasal microemulsion treatment can attenuate allergen challenge-induced nasal symptoms and plasma exudation in allergic rhinitis. We hypothesize that the mechanism of action involves modification of the allergen-mucosa interaction. The present observation suggests a novel principle for prevention in allergic rhinitis. Objective. To evaluate a specific microemulsion as a treatment for allergic rhinitis in an acute allergen challenge model. Patients and methods. Patients with allergic rhinitis were examined out of the pollen season. Treatment with a single dose of a specific microemulsion was given in a single-blind, placebo-controlled, and crossover design using a nasal pool device. Nasal allergen challenges were carried out and symptoms of allergic rhinitis were scored. Furthermore, nasal lavages were performed and levels of the plasma protein alpha(2)-macroglobulin were measured as an index of exudative inflammation. Results. The allergen challenges produced significant increases in nasal symptoms (p = 0.007) and in nasal lavage fluid levels of alpha(2)-macroglobulin (p = 0.008). The challenge-induced symptoms as well as the plasma exudation were attenuated by treatment with the microemulsion (p = 0.016 and 0.012, respectively, compared with placebo).
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| 17. |
- Andersson, Morgan, et al.
(författare)
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Wine produced by ecological methods produces relatively little nasal blockage in wine-sensitive subjects.
- 2009
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Ingår i: Acta Oto-Laryngologica. - 1651-2251. ; 129:11, s. 1232-1236
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Tidskriftsartikel (refereegranskat)abstract
- CONCLUSION: Subjects with self-reported nasal symptoms following consumption of red wine may respond with less nasal blockage to a wine produced with ecological methods than to wine not labelled as ecologically produced. OBJECTIVE: To compare nasal symptoms following intake of three different wines--one that was ecologically produced and two that were traditionally produced. SUBJECTS AND METHODS: Individuals with self-reported nasal symptoms following consumption of red wine were subjected to controlled intake of three different wines in a double-blinded, randomized, and crossover design. Nasal symptoms and peak nasal inspiratory flow (PNIF) were monitored before and 15, 30, 45, and 60 min following intake of wine. RESULTS: All wines produced nasal symptoms, notably nasal blockage. While blockage scores did not differ between the two non-ecological wines, the ecological wine was associated with significantly lower blockage scores, as compared with both the other wines.
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| 18. |
- Andreasson, Ulrika, et al.
(författare)
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The human IgE-encoding transcriptome to assess antibody repertoires and repertoire evolution
- 2006
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 362:2, s. 212-227
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Tidskriftsartikel (refereegranskat)abstract
- Upon encounter with antigen, the B lymphocyte population responds by producing a diverse set of antigen-specific antibodies of various isotypes. The vast size of the responding populations makes it very difficult to study clonal evolution and repertoire composition occurring during these processes in humans. Here, we have explored an approach utilizing the H-EPSILON-encoding transcriptome to investigate aspects of repertoire diversity during the season of antigen exposure. We show through sequencing of randomly picked transcripts that the sizes of patients' repertoires are relatively small. This specific aspect of the transcriptome allows us to construct evolutionary trees pinpointing features of somatic hypermutation as it occurs in humans. Despite the small size of the repertoires, they are highly diverse with respect to VDJ gene usage, suggesting that the H-EPSILON-encoding transcriptome is a faithful mimic of other class-switched isotypes. Importantly, it is possible to use antibody library and selection technologies to define the specificity of clonotypes identified by random sequencing. The small size of the H-EPSILON-encoding transcriptome of peripheral blood B cells, the simple identification of clonally related sets of genes in this population, and the power of library and selection technologies ensure that this approach will allow us to investigate antibody evolution in human B lymphocytes of known specificity. As H-EPSILON repertoires show many of the hallmarks of repertoires encoding other isotypes, we suggest that studies of this type will have an impact on our understanding of human antibody evolution even beyond that occurring in the IgE-producing B cell population.
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| 19. |
- Askmyr, David, et al.
(författare)
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Pattern recognition receptor expression and maturation profile of dendritic cell subtypes in human tonsils and lymph nodes
- 2021
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Ingår i: Human Immunology. - : Elsevier BV. - 0198-8859. ; 82:12, s. 976-981
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DCs) with capacity of antigen cross-presentation are of key interest for immunotherapy against cancer as they can induce antigen-specific cytotoxic T lymphocyte (CTL) responses. This study describes frequencies of DC subtypes in human tonsils and lymph nodes, and phenotypic aspects that may be targeted by adjuvant measures. From human tonsils and neck lymph nodes, DCs were identified through flow cytometry, and subsets of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were investigated. Maturity status was assessed and surface receptors with CTL-promoting potentials were studied. CD123+ pDCs as well as CD1c+, CD141+, and CD1c-CD141- mDCs were detected in tonsils and lymph nodes. Both sites featured a similar presence of DC subsets, with CD123+ pDC being dominant and CD141+ mDCs least frequent. Based on CD80/CD86 expression, all DC subtypes featured a low degree of maturation. Expression of pattern recognition receptors (PRRs) CD206, CD207, DC-SIGN, TLR2, and TLR4, as well as the chemokine receptor XCR1, indicated DC subset-specific receptor profiles. We conclude that tonsils and lymph nodes share common features in terms of DC subset frequency and maturation as well as PRR and XCR1 expression pattern. Our work suggests that both sites may be considered for vaccine deposition in DC-mediated immunotherapy.
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| 20. |
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