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| 2. |
- Thunqvist, P., et al.
(författare)
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Lung Function at 8 and 16 Years After Moderate-to-Late Preterm Birth: A Prospective Cohort Study
- 2016
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 137:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Knowledge regarding lung function after moderately preterm birth is limited. We therefore investigated lung function at early school age and adolescence among children born moderately preterm. METHODS: Data were used from the Swedish prospective birth cohort BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology study; N = 4089), with a 4.8% prevalence of moderate to late preterm birth defined as a gestational age of 32 to 36 weeks. Participants underwent spirometry at ages 8 and 16 years, and impulse oscillometry additionally at age 16 years. In total, 2621 children (149 preterm and 2472 term) provided lung function data. RESULTS: At age 8 years, adjusted forced expiratory volume in 1 second was lower in preterm female subjects (-64 mL [95% confidence interval (CI): -118 to -10]) compared with term female subjects but not in preterm male subjects. At age 16 years, both genders in the preterm group demonstrated lower forced expiratory volume in 1 second (female subjects: -116 mL [95% CI: -212 to -20]; male subjects: -177 mL [95% CI: -329 to -25]) compared with the term group. For the preterm group, impulse oscillometry demonstrated higher adjusted resistance at 5 Hz (female subjects: 31.3 Pa.L-1.s(-1) [95% CI: 6.3 to 56.3]; male subjects: 34.9 Pa.L-1.s(-1) [95% CI: 12.0 to 57.7]) and frequency dependence of resistance (resistance at 5 and 20 Hz) for male subjects (20.9 Pa.L-1.s(-1) [95% CI: 9.8 to 31.9]) compared with the term group. CONCLUSIONS: Measures of airway function assessed in adolescence were reduced in children born moderate to late preterm, and no catch-up in lung function between ages 8 and 16 years was observed.
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| 3. |
- Hallberg, J, et al.
(författare)
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Asthma phenotypes and lung function up to 16 years of age-the BAMSE cohort.
- 2015
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 70:6, s. 667-673
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Tidskriftsartikel (refereegranskat)abstract
- Asthma is a disease affecting many locations throughout the airway. Most studies have used spirometry as the primary assessment of airway obstruction, a method that may be less sensitive in regard to peripheral airway obstruction. The aim of this study was to elucidate the associations between asthma phenotypes based on age of onset and duration of symptoms, and (i) spirometry and (ii) small airway involvement measured by impulse oscillometry (IOS) in adolescence.
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| 4. |
- Rydberg, Lennart, 1944, et al.
(författare)
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Extracorporeal ("ex vivo") connection of pig kidneys to humans. II. The anti-pig antibody response.
- 1996
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Ingår i: Xenotransplantation. - : Wiley. - 0908-665X .- 1399-3089. ; 3:4, s. 340-53
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Tidskriftsartikel (refereegranskat)abstract
- Pig kidneys were extracorporeally "ex vivo" connected to the circulation of two volunteer male dialysis patients (Breimer et al., this issue). The patients were pretreated by daily plasmapheresis for 3 consecutive days, which reduced the anti-pig lymphocytotoxic titer from 8 to 2 in the first patient and from 8 to 1 in the second patient. The anti-pig hemagglutinating titers were reduced from 32 to 4 in the first patient and from 2 to 1 in the second patient. No drugs, except heparin, were given. The perfusion lasted for 65 min in patient 1 and the experiment was terminated due to increased vascular resistance in the pig kidney. Ultrastructural investigation showed a picture similar to a hyperacute vascular rejection. Immunohistochemical studies showed a weak staining of IgM antibodies, but no IgG in the small arteries and glomeruli. The pig kidney of patient 2 was perfused for 15 min and the experiment terminated due to serious side effects of the patient. Light and electron microscopical investigation showed virtually no structural changes of the kidney tissue and immunostaining for human antibodies was negative. In both patients, serum samples collected 2-5 weeks postperfusion showed a strong anti-pig antibody titer rise (up to 512) which thereafter declined but stabilized on a higher level than before the experiment. The antibody response in the two patients was different. In patient 1, the major anti-pig antibodies directed to carbohydrate antigens were of IgG (IgG1 and IgG2 subclasses) type, while the IgM response was less prominent and virtually no IgA antibodies were produced. Despite the short duration of the perfusion in patient 2, a humoral immune response was seen that was mainly confined to the IgA immunoglobulin class (IgA1 subclass). Blood group glycospingolipid fractions, prepared from the contralateral kidney of the donor pigs, were used for immunostaining with patient serum samples. In both patients, the antibodies produced after the perfusion, mainly recognized the Galα1-3Gal epitope both as part of the "linear B" pentasaccharide but also on more complex carbohydrate structures. Patient 1 was HLA-immunized before the experiment due to a kidney allograft and had a panel reactivity of 85% before the perfusion. No change in the panel reactivity of HLA-antibodies was found after the perfusion experiments. Patient 2 had no HLA antibodies before and remained negative after the perfusion. Patient serum samples collected before and after the perfusion were tested for reactivity against human endothelial cell lines. No antibodies were generated.
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| 5. |
- Schultz, E. S., et al.
(författare)
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Early life determinants of lung function change from childhood to adolescence
- 2018
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 139, s. 48-54
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Little is known about how perinatal and childhood factors influence lung function change between childhood and adolescence. Objectives: To investigate possible early life predictors of change in FEV1 between age 8 and 16 years. In addition, to investigate possible predictors of having persistently low lung function (FEV1 < 25th percentiles both at age 8 and 16) up to adolescence. Methods: The BAMSE birth cohort study collected data throughout childhood on environmental factors, individual characteristics, and spirometric measures at 8 and 16 years (n = 1425). Associations between early life predictors (n = 31) and FEV1 increase between 8 and 16 years were assessed with linear regression. Predictors of having persistently low lung function were examined. Results: Few factors were consistently associated with altered lung function growth, although low birth weight, asthma heredity (paternal), secondhand smoke in infancy, and season of birth had a significant impact (p-value <= 0.01). The majority of subjects stayed however within the same category of lung function between ages 8 and 16 years (in total 821/1425 = 58%). Predictors associated with having persistently low lung function were gestational age, secondhand smoke (at 2 and 8 years of age), and factors related to lower respiratory tract infections in infancy. Conclusions: In summary, rather few exposures in childhood were identified to have a significant impact on lung function growth between childhood and adolescence. Our data support previous study findings indicating that lung function development is influenced by factors before birth and in infancy, including second hand tobacco smoke.
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| 6. |
- Thacher, J. D., et al.
(författare)
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Tobacco smoke exposure in early life and adolescence in relation to lung function
- 2018
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 51:6
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Tidskriftsartikel (refereegranskat)abstract
- Maternal smoking during pregnancy is associated with impaired lung function among young children, but less is known about long-term effects and the impact of adolescents' own smoking. We investigated the influence of maternal smoking during pregnancy, secondhand smoke exposure and adolescent smoking on lung function at age 16 years. The BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology) birth cohort collected information on participants' tobacco smoke exposure through repeated questionnaires, and measured saliva cotinine concentrations at age 16 years. Participants performed spirometry and impulse oscillometry (IOS) at age 16 years (n=2295). Exposure to maternal smoking during pregnancy was associated with reduced forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio of -1.1% (95% CI -2.0 to -0.2%). IOS demonstrated greater resistance at 5-20 Hz (R5-20) in participants exposed to maternal smoking during pregnancy. Adolescents who smoked had reduced FEV1/FVC ratios of -0.9% (95% CI -1.8 to -0.1%) and increased resistance of 6.5 Pa.L-1.s (95% CI 0.7 to 12.2 Pa.L-1.s) in R5-20. Comparable associations for FEV1/FVC ratio were observed for cotinine concentrations, using. 12 ng.mL(-1) as a cut-off for adolescent smoking. Maternal smoking during pregnancy was associated with lower FEV1/FVC ratios and increased airway resistance. In addition, adolescent smoking appears to be associated with reduced FEV1/FVC ratios and increased peripheral airway resistance.
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| 7. |
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| 8. |
- Borenäs, Marcus, et al.
(författare)
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ALK ligand ALKAL2 potentiates MYCN-driven neuroblastoma in the absence of ALK mutation
- 2021
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Ingår i: EMBO Journal. - : John Wiley & Sons. - 0261-4189 .- 1460-2075. ; 40:3
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Tidskriftsartikel (refereegranskat)abstract
- High‐risk neuroblastoma (NB) is responsible for a disproportionate number of childhood deaths due to cancer. One indicator of high‐risk NB is amplification of the neural MYC (MYCN) oncogene, which is currently therapeutically intractable. Identification of anaplastic lymphoma kinase (ALK) as an NB oncogene raised the possibility of using ALK tyrosine kinase inhibitors (TKIs) in treatment of patients with activating ALK mutations. 8–10% of primary NB patients are ALK‐positive, a figure that increases in the relapsed population. ALK is activated by the ALKAL2 ligand located on chromosome 2p, along with ALK and MYCN, in the “2p‐gain” region associated with NB. Dysregulation of ALK ligand in NB has not been addressed, although one of the first oncogenes described was v‐sis that shares > 90% homology with PDGF. Therefore, we tested whether ALKAL2 ligand could potentiate NB progression in the absence of ALK mutation. We show that ALKAL2 overexpression in mice drives ALK TKI‐sensitive NB in the absence of ALK mutation, suggesting that additional NB patients, such as those exhibiting 2p‐gain, may benefit from ALK TKI‐based therapeutic intervention.
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| 9. |
- Borenäs, Marcus, et al.
(författare)
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ALK signaling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition
- 2024
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 1091-6490. ; 121:1
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Tidskriftsartikel (refereegranskat)abstract
- High-risk neuroblastoma (NB) is a significant clinical challenge. MYCN and Anaplastic Lymphoma Kinase (ALK), which are often involved in high-risk NB, lead to increased replication stress in cancer cells, suggesting therapeutic strategies. We previously identified an ATR (ataxia telangiectasia and Rad3-related)/ALK inhibitor (ATRi/ALKi) combination as such a strategy in two independent genetically modified mouse NB models. Here, we identify an underlying molecular mechanism, in which ALK signaling leads to phosphorylation of ATR and CHK1, supporting an effective DNA damage response. The importance of ALK inhibition is supported by mouse data, in which ATRi monotreatment resulted in a robust initial response, but subsequent relapse, in contrast to a 14-d ALKi/ATRi combination treatment that resulted in a robust and sustained response. Finally, we show that the remarkable response to the 14-d combined ATR/ALK inhibition protocol reflects a robust differentiation response, reprogramming tumor cells to a neuronal/Schwann cell lineage identity. Our results identify an ability of ATR inhibition to promote NB differentiation and underscore the importance of further exploring combined ALK/ATR inhibition in NB, particularly in high-risk patient groups with oncogene-induced replication stress.
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| 10. |
- Cakir, B., et al.
(författare)
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Thrombocytopenia is associated with severe retinopathy of prematurity
- 2018
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Ingår i: Jci Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 3:19
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Tidskriftsartikel (refereegranskat)abstract
- Retinopathy of prematurity (ROP) is characterized by abnormal retinal neovascularization in response to vessel loss. Platelets regulate angiogenesis and may influence ROP progression. In preterm infants, we assessed ROP and correlated with longitudinal postnatal platelet counts (n = 202). Any episode of thrombocytopenia (< 100 x 10(9)/l) at >= 30 weeks postmenstrual age (at onset of ROP) was independently associated with severe ROP, requiring treatment. Infants with severe ROP also had a lower weekly median platelet count compared with infants with less severe ROP. In a mouse oxygen-induced retinopathy model of ROP, platelet counts were lower at P17 (peak neovascularization) versus controls. Platelet transfusions at P15 and P16 suppressed neovascularization, and platelet depletion increased neovascularization. Platelet transfusion decreased retinal of vascular endothelial growth factor A (VEGFA) mRNA and protein expression; platelet depletion increased retinal VEGFA mRNA and protein expression. Resting platelets with intact granules reduced neovascularization, while thrombin-activated degranulated platelets did not. These data suggest that platelet releasate has a local antiangiogenic effect on endothelial cells to exert a downstream suppression of VEGFA in neural retina. Low platelet counts during the neovascularization phase in ROP is significantly associated with the development of severe ROP in preterm infants. In a murine model of retinopathy, platelet transfusion during the period of neovascularization suppressed retinopathy.
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