| 1. |
- Che, K. F., et al.
(author)
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The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers
- 2018
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In: Clinical Science. - : Portland Press Ltd.. - 0143-5221 .- 1470-8736. ; 132:9, s. 959-983
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Journal article (peer-reviewed)abstract
- Long-term tobacco smokers with chronic obstructive pulmonary disease (COPD) or chronic bronchitis display an excessive accumulation of neutrophils in the airways; an inflammation that responds poorly to established therapy. Thus, there is a need to identify new molecular targets for the development of effective therapy. Here, we hypothesized that the neutrophil-mobilizing cytokine interleukin (IL)-26 (IL-26) is involved in airway inflammation amongst long-term tobacco smokers with or without COPD, chronic bronchitis or colonization by pathogenic bacteria. By analyzing bronchoalveolar lavage (BAL), bronchail wash (BW) and induced sputum (IS) samples, we found increased extracellular IL-26 protein in the airways of long-term smokers in vivo without further increase amongst those with clinically stable COPD. In human alveolar macrophages (AM) in vitro, the exposure to water-soluble tobacco smoke components (WTC) enhanced IL-26 gene and protein. In this cell model, the same exposure increased gene expression of the IL-26 receptor complex (IL10R2 and IL20R1) and nuclear factor kappa B (NF-kappa B); a proven regulator of IL-26 production. In the same cell model, recombinant human IL-26 in vitro caused a concentration-dependent increase in the gene expression of NF-kappa B and several pro-inflammatory cytokines. In the long-term smokers, we also observed that extracellular IL-26 protein in BAL samples correlates with measures of lung function, tobacco load, and several markers of neutrophil accumulation. Extracellular IL-26 was further increased in long-term smokers with exacerbations of COPD (IS samples), with chronic bronchitis (BAL samples) or with colonization by pathogenic bacteria (IS and BW samples). Thus, IL-26 in the airways emerges as a promising target for improving the understanding of the pathogenic mechanisms behind several pulmonary morbidities in long-term tobacco smokers.
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| 2. |
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| 3. |
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| 4. |
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| 5. |
- Högman, Marieann, et al.
(author)
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Effects of growth and aging on the reference values of pulmonary nitric oxide dynamics in healthy subjects
- 2017
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In: Journal of Breath Research. - : IOP Publishing. - 1752-7155 .- 1752-7163. ; 11:4
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Journal article (peer-reviewed)abstract
- The lung just like all other organs is affected by age. The lung matures by the age of 20 and age-related changes start around middle age, at 40-50 years. Exhaled nitric oxide (FENO) has been shown to be age, height and gender dependent. We hypothesize that the nitric oxide (NO) parameters alveolar NO (CANO), airway flux (JawNO), airway diffusing capacity (DawNO) and airway wall content (CawNO) will also demonstrate this dependence. Data from healthy subjects were gathered by the current authors from their earlier publications in which healthy individuals were included as control subjects. Healthy subjects (n = 433) ranged in age from 7 to 78 years. Age-stratified reference values of the NO parameters were significantly different. Gender differences were only observed in the 20-49 age group. The results from the multiple regression models in subjects older than 20 years revealed that age, height and gender interaction together explained 6% of variation in FENO at 50 ml s-1 (FENO50), 4% in JawNO, 16% in CawNO, 8% in DawNO and 12% in CANO. In conclusion, in this study we have generated reference values for NO parameters from an extended NO analysis of healthy subjects. This is important in order to be able to use these parameters in clinical practice.
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| 6. |
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| 7. |
- Sellgren, C. M., et al.
(author)
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GRK3 deficiency elicits brain immune activation and psychosis
- 2021
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 6820-6832
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Journal article (peer-reviewed)abstract
- The G protein-coupled receptor kinase (GRK) family member protein GRK3 has been linked to the pathophysiology of schizophrenia and bipolar disorder. Expression, as well as protein levels, of GRK3 are reduced in post-mortem prefrontal cortex of schizophrenia subjects. Here, we investigate functional behavior and neurotransmission related to immune activation and psychosis using mice lacking functional Grk3 and utilizing a variety of methods, including behavioral, biochemical, electrophysiological, molecular, and imaging methods. Compared to wildtype controls, the Grk3(-/-) mice show a number of aberrations linked to psychosis, including elevated brain levels of IL-1 beta, increased turnover of kynurenic acid (KYNA), hyper-responsiveness to D-amphetamine, elevated spontaneous firing of midbrain dopamine neurons, and disruption in prepulse inhibition. Analyzing human genetic data, we observe a link between psychotic features in bipolar disorder, decreased GRK expression, and increased concentration of CSF KYNA. Taken together, our data suggest that Grk3(-/-) mice show face and construct validity relating to the psychosis phenotype with glial activation and would be suitable for translational studies of novel immunomodulatory agents in psychotic disorders.
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| 8. |
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| 9. |
- Cai, Xuesong, et al.
(author)
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Characterizing the Small-Scale Fading for Low Altitude UAV Channels
- 2021
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In: ICWMC 2021 : The Seventeenth International Conference on Wireless and Mobile Communications - The Seventeenth International Conference on Wireless and Mobile Communications. - 9781612088785 ; , s. 16-19
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Conference paper (peer-reviewed)abstract
- In this contribution, a recently conducted measurement campaign in a suburban scenario for the Unmanned Aerial Vehicle (UAV) Air-to-Ground (A2G) radio channel is introduced.The downlink signals in an in-service Long Term Evolution (LTE) network were collected and utilized to extract the Channel Impulse Responses (CIRs). A high-resolution parameter estimation algorithm derived based on the Space-Alternating Generalized Expectation-maximization (SAGE) principle is applied to estimate the delays, Doppler frequencies and complex amplitudes of Multi Path Components (MPCs) from the CIRs. Based on the MPC estimation results, fast fading characteristics of the A2G channels are investigated. It is found that the Rician distribution models the fast fading the best compared to Nakagami, Lognormal and Rayleigh distributions. Rician K factors are also calculated for the A2G channels.
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| 10. |
- Cai, Xuesong, et al.
(author)
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Power Allocation for Uplink Communications of Massive Cellular-Connected UAVs
- 2023
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In: IEEE Transactions on Vehicular Technology. - 0018-9545. ; 72:7, s. 8797-8811
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Journal article (peer-reviewed)abstract
- Cellular-connected unmanned aerial vehicle (UAV) has attracted a surge of research interest in both academia and industry. To support aerial user equipment (UEs) in the existing cellular networks, one promising approach is to assign a portion of the system bandwidth exclusively to the UAV-UEs. This is especially favorable for use cases where a large number of UAV-UEs are exploited, e.g., for package delivery close to a warehouse. Although the nearly line-of-sight (LoS) channels can result in higher powers received, UAVs can in turn cause severe interference to each other in the same frequency band. In this contribution, we focus on the uplink communications of massive cellular-connected UAVs. Different power allocation algorithms are proposed to either maximize the minimal spectrum efficiency (SE) or maximize the overall SE to cope with severe interference based on the successive convex approximation (SCA) principle. One of the challenges is that a UAV can affect a large area meaning that many more UAV-UEs must be considered in the optimization problem, which is essentially different from that for terrestrial UEs. The necessity of single-carrier uplink transmission further complicates the problem. Nevertheless, we find that the special property of large coherent bandwidths and coherent times of the propagation channels can be leveraged. The performances of the proposed algorithms are evaluated via extensive simulations in the full-buffer transmission mode and bursty-traffic mode. Results show that the proposed algorithms can effectively enhance the uplink SEs. This work can be considered the first attempt to deal with the interference among massive cellular-connected UAV-UEs with optimized power allocations.
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| 11. |
- Fang, Cheng, et al.
(author)
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Indoor-indoor and indoor-outdoor propagation trial results at 2.6 GHz
- 2012
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In: Antennas and Propagation Conference (LAPC), 2012 Loughborough. - : IEEE. - 9781467322195 ; , s. 6403064-
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Conference paper (peer-reviewed)abstract
- This paper presents delay spread, coherence bandwidth, and angle-of-arrival statistics derived from an extensive MIMO channel measurement campaign carried out at a central frequency of 2.6GHz. The measurement scenarios include indoor-indoor, indoor-outdoor and indoor-outdoor-indoor. The results are useful for analytical and performance studies of post-3G wireless communication systems such as femtocell design and deployment.
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| 12. |
- Garcia-Ryde, Martin, et al.
(author)
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Lung Fibroblasts from Chronic Obstructive Pulmonary Disease Subjects Have a Deficient Gene Expression Response to Cigarette Smoke Extract Compared to Healthy
- 2023
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In: International journal of chronic obstructive pulmonary disease. - 1178-2005. ; 18, s. 2999-3014
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIM: Cigarette smoking is the most common cause of chronic obstructive pulmonary disease (COPD) but more mechanistic studies are needed. Cigarette smoke extract (CSE) can elicit a strong response in many COPD-related cell types, but no studies have been performed in lung fibroblasts. Therefore, we aimed to investigate the effect of CSE on gene expression in lung fibroblasts from healthy and COPD subjects.PATIENTS AND METHODS: Primary lung fibroblasts, derived from six healthy and six COPD subjects (all current or ex-smokers), were either unstimulated (baseline) or stimulated with 30% CSE for 4 h prior to RNA isolation. The mRNA expression levels were measured using the NanoString nCounter Human Fibrosis V2 panel (760 genes). Pathway enrichment was assessed for unique gene ontology terms of healthy and COPD.RESULTS: At baseline, a difference in the expression of 17 genes was found in healthy and COPD subjects. Differential expression of genes after CSE stimulation resulted in significantly less changes in COPD lung fibroblasts (70 genes) than in healthy (207 genes), with 51 genes changed in both. COPD maintained low NOTCH signaling throughout and upregulated JUN >80%, indicating an increase in apoptosis. Healthy downregulated the Mitogen-activated protein kinase (MAPK) signaling cascade, including a ≥50% reduction in FGF2, CRK, TGFBR1 and MEF2A. Healthy also downregulated KAT6A and genes related to cell proliferation, all together indicating possible cell senescence signaling.CONCLUSION: Overall, COPD lung fibroblasts responded to CSE stimulation with a very different and deficient expression profile compared to healthy. Highlighting that stimulated healthy cells are not an appropriate substitute for COPD cells which is important when investigating the mechanisms of COPD.
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| 13. |
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| 14. |
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| 15. |
- Jesenak, Milos, et al.
(author)
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Eosinophils—from cradle to grave
- 2023
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In: Allergy: European Journal of Allergy and Clinical Immunology. - 0105-4538. ; 78:12, s. 3077-3102
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Journal article (peer-reviewed)abstract
- Over the past years, eosinophils have become a focus of scientific interest, especially in the context of their recently uncovered functions (e.g. antiviral, anti-inflammatory, regulatory). These versatile cells display both beneficial and detrimental activities under various physiological and pathological conditions. Eosinophils are involved in the pathogenesis of many diseases which can be classified into primary (clonal) and secondary (reactive) disorders and idiopathic (hyper)eosinophilic syndromes. Depending on the biological specimen, the eosinophil count in different body compartments may serve as a biomarker reflecting the underlying pathophysiology and/or activity of distinct diseases and as a therapy-driving (predictive) and monitoring tool. Personalized selection of an appropriate therapeutic strategy directly or indirectly targeting the increased number and/or activity of eosinophils should be based on the understanding of eosinophil homeostasis including their interactions with other immune and non-immune cells within different body compartments. Hence, restoring as well as maintaining homeostasis within an individual's eosinophil pool is a goal of both specific and non-specific eosinophil-targeting therapies. Despite the overall favourable safety profile of the currently available anti-eosinophil biologics, the effect of eosinophil depletion should be monitored from the perspective of possible unwanted consequences.
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| 16. |
- Nilsson, A. M., et al.
(author)
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Increased B-cell activating factor, interleukin-6, and interleukin-8 in induced sputum from primary Sjogrens syndrome patients
- 2019
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In: Scandinavian Journal of Rheumatology. - : TAYLOR & FRANCIS LTD. - 0300-9742 .- 1502-7732. ; 48:2, s. 149-156
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Journal article (peer-reviewed)abstract
- Objective: Small airway disease and chronic obstructive pulmonary disease are common in primary Sjogrens syndrome (pSS). However, the underlying inflammatory mechanisms behind pSS-associated airway disease have not been studied in detail. We therefore wanted to study cytokine and leucocyte levels in induced sputum in never-smoking patients with pSS. Method: Induced sputum cytokines and leucocytes were assessed in 20 never-smoking patients with pSS and 19 age- and gender-matched population-based controls. In addition, pulmonary function, disease activity, respiratory symptoms, and inflammatory and serological features of pSS were assessed. Results: B-cell activating factor (BAFF), interleukin-6 (IL-6) and IL-8 were significantly increased in induced sputum in pSS patients compared to population-based controls, while IL-1 beta, interferon-alpha, and tumour necrosis factor-alpha levels and leucocytes were not. The proportion of lymphocytes and BAFF levels in induced sputum correlated significantly in pSS patients. However, cytokine levels in induced sputum were not associated with pulmonary function tests, disease activity, respiratory symptoms, or serological features of pSS. Conclusion: The increase in BAFF, IL-6, and IL-8 in induced sputum suggests a specific ongoing inflammatory disease process in the airways in pSS patients. Its association with pSS-associated airway disease needs to be further examined in future larger studies.
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| 17. |
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| 18. |
- Scheja, Agneta, et al.
(author)
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BAL fluid derived fibroblasts differ from biopsy derived fibroblasts in systemic sclerosis.
- 2007
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 29:3, s. 446-452
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Journal article (peer-reviewed)abstract
- Growth of fibroblasts from bronchoalveolar lavage fluid (BALF) in patients with systemic sclerosis (SSc) has previously been described. The purpose of the present study was to characterise fibroblasts from BALF and bronchial biopsies from SSc patients with alveolitis and from controls, to analyse fibroblast proliferation, migration, stress fibres and proteoglycan production. BALF and bronchial biopsies were collected from 10 patients with SSc and alveolitis and from 15 controls. Outgrowth of fibroblasts was observed from the BALF of four patients, particularly in those with a markedly increased percentage of eosinophils in BALF, but not in any member of the control group. Increased levels of granulocyte-macrophage colony-stimulating factor, correlating with the percentage of eosinophils in BALF, were found in patients when compared with controls. Fibroblasts from BALF showed an elongated, mobile phenotype and increased proteoglycan production compared to the corresponding biopsy fibroblasts. In conclusion, outgrowth of fibroblasts with an altered phenotype is reported from bronchoalveolar lavage fluid in systemic sclerosis patients with alveolitis and an increased percentage of eosinophils in the bronchoalveolar lavage fluid. These findings indicate a possible role for eosinophil-fibroblast interaction in pulmonary fibrosis in systemic sclerosis.
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| 19. |
- Stenberg, H., et al.
(author)
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Small airway involvement in the late allergic response in asthma
- 2017
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In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894. ; 47:12, s. 1555-1565
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Journal article (peer-reviewed)abstract
- Background: Allergy and asthma are closely linked. Inhalation of allergen induces an early allergic response (EAR) within the airways of allergic asthmatic subjects, which is followed by a late allergic response (LAR) in approximately 50% of the subjects. The LAR is defined as a drop in forced expiratory volume in 1 second (FEV1) from baseline usually occurring 4-8 hours after exposure and is believed to affect small airways. However, FEV1 is insensitive to changes in small airway physiology. Objective: Our aim was to investigate and compare the pathophysiological processes in large and small airways during the EAR and the LAR and to characterize subjects with both an EAR and a LAR (dual responders) versus those with an EAR only (single responders). Methods: Thirty-four subjects with allergic asthma underwent an inhaled allergen challenge. Lung physiology was assessed by spirometry, impulse oscillometry (IOS), body plethysmography, inert gas washout, single breath methane dilution carbon monoxide diffusion and exhaled breath temperature (EBT), at baseline and repeatedly for 23 hours post-allergen challenge. Results: Peripheral airway resistance, air trapping and ventilation heterogeneity were significantly increased in dual responders (n = 15) compared to single responders (n = 19) 6-8 hours post-challenge. Parameters of peripheral airway resistance and ventilation heterogeneity, measured with IOS and inert gas washout, respectively, correlated at baseline and during the allergic airway response in all subjects. Conclusion: The LAR involves increased resistance and ventilation defects within the peripheral airways. Alternative definitions of the LAR including small airways pathophysiology could be considered. Clinical relevance: Small airway dysfunction during the LAR suggests that dual responders may have more extensive airway pathology and underscores the relevance of small airways assessment in asthma.
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| 20. |
- Tian, Guoda, et al.
(author)
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Modified Gold Sequence for Positioning Enhancement in NB-IoT
- 2019
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In: 2019 IEEE Wireless Communications and Networking Conference, WCNC 2019. - 1525-3511. - 9781538676462 ; 2019-April
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Conference paper (peer-reviewed)abstract
- Positioning is an essential feature in Narrow-Band Internet-of-Things (NB-IoT) systems. Observed Time Difference of Arrival is one of the supported positioning techniques for NB-IoT. It utilizes the downlink NB positioning reference signal (NPRS) generated based on a length-31 Gold sequence. Although a Gold sequence has good auto-correlation and cross-correlation properties, the correlation properties of NPRS in NB-IoT are still sub-optimal. The reason is mainly due to two facts: the number of NPRS symbols in each subframe is limited, and the featured sampling-rate is low. In this paper, we propose to modify the NPRS generation by exploiting the cross-correlation function of the NPRS. That is, for each orthogonal frequency division multiplexing (OFDM) symbol we generate the first NPRS symbol as specified in the current standard, i.e., a Gold sequence; while the second OFDM symbol is set to the additive inverse of the first one. Our simulation results show that the proposed NPRS sequence results in improving the correlation properties, particularly with respect to the cross-correlation property. Furthermore, 15% -30% positioning-accuracy improvements can be attained with the proposed method, compared to the legacy one under both Additive White Gaussian Noise and Extended-Pedestrian-A channels. The proposed NPRS sequence can also be applied to other similar systems, such as long-term-evolution (LTE).
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| 21. |
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| 22. |
- Tufvesson, E., et al.
(author)
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Inducible nitric oxide synthase expression is increased in the alveolar compartment of asthmatic patients
- 2017
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In: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538. ; 72:4, s. 627-635
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Journal article (peer-reviewed)abstract
- Introduction: Increased exhaled nitric oxide (NO) levels in asthma are suggested to be through inducible NO synthase (iNOS). The aim of this study was to investigate the expression of iNOS in bronchoalveolar lavage (BAL) cells and tissue from central and peripheral airways and compare it with the exhaled bronchial and alveolar NO levels in patients with asthma vs a control group. Methods: Thirty-two patients with asthma (defined as controlled or uncontrolled according to Asthma Control Test score cut-off: 20) and eight healthy controls were included. Exhaled NO was measured, and alveolar concentration and bronchial flux were calculated. iNOS was measured in central and peripheral lung biopsies, as well as BAL cells. Bronchoalveolar lavage macrophages were stimulated in vitro, and iNOS expression and NO production were investigated. Results: Expression of iNOS was increased in central airway tissue and the alveolar compartment in uncontrolled as compared to controlled asthmatics and healthy controls. There were no differences, however, in iNOS mRNA levels in total BAL cells in uncontrolled as compared to controlled asthma. Bronchoalveolar lavage cell mRNA levels of iNOS or iNOS expression in central and alveolar tissue did not relate to alveolar NO, nor to bronchial flux of NO. In vitro stimulation with leukotriene D4 increased iNOS mRNA levels and NO production in cultured BAL macrophages. Conclusion: The levels of both bronchial and alveolar iNOS are increased in uncontrolled as compared to controlled asthma. However, levels of iNOS in BAL macrophages were not reflected by alveolar NO. Both central and distal iNOS levels may reflect responsiveness to steroid treatment.
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| 23. |
- Tufvesson Stiller, Helena, et al.
(author)
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Health Related Quality of Life in Melanoma Patients : characterization of a Swedish cohort
- 2020
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In: British Journal of Dermatology. - : Wiley-Blackwell. - 0007-0963 .- 1365-2133. ; 182:2, s. 506-508
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Journal article (peer-reviewed)abstract
- Only few studies that have investigated the Health-Related Quality of Life (HR-QoL) in melanoma patients 1-4 , reviewed in Chernyshov et al.5 . This is to the best of our knowledge the first population-based study investigating HR-QoL in proximity to the time the patient has received melanoma diagnosis. A cross-sectional survey, approved by the ethics committee in Umeå, employing the Swedish European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30v.3.0) was performed.
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