| 1. |
- Amin, H., et al.
(författare)
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Indoor Airborne Microbiome and Endotoxin: Meteorological Events and Occupant Characteristics Are Important Determinants
- 2023
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 57:32, s. 11750-11766
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Tidskriftsartikel (refereegranskat)abstract
- Minimal research exists onthe factors influencing the indoorbacterial community. Despite their proposed importance for health,here we report environmental factors influencing the composition ofthe indoor bacterial communities. Airborne bacteria and endotoxin may affect asthma andallergies.However, there is limited understanding of the environmental determinantsthat influence them. This study investigated the airborne microbiomesin the homes of 1038 participants from five cities in Northern Europe:Aarhus, Bergen, Reykjavik, Tartu, and Uppsala. Airborne dust particleswere sampled with electrostatic dust fall collectors (EDCs) from theparticipants' bedrooms. The dust washed from the EDCs'clothes was used to extract DNA and endotoxin. The DNA extracts wereused for quantitative polymerase chain (qPCR) measurement and 16SrRNA gene sequencing, while endotoxin was measured using the kineticchromogenic limulus amoebocyte lysate (LAL) assay. The results showedthat households in Tartu and Aarhus had a higher bacterial load anddiversity than those in Bergen and Reykjavik, possibly due to elevatedconcentrations of outdoor bacterial taxa associated with low precipitationand high wind speeds. Bergen-Tartu had the highest difference (ANOSIM R = 0.203) in & beta; diversity. Multivariate regressionmodels showed that & alpha; diversity indices and bacterial and endotoxinloads were positively associated with the occupants' age, numberof occupants, cleaning frequency, presence of dogs, and age of thehouse. Further studies are needed to understand how meteorologicalfactors influence the indoor bacterial community in light of climatechange.
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| 2. |
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| 3. |
- Jögi, Annika, et al.
(författare)
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Patched 2, located in 1p32-34, is not mutated in high stage neuroblastoma tumors
- 2000
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Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 16:5, s. 943-949
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Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma is a childhood malignancy originating from cells of the sympathetic nervous system, exhibiting a marked diversity in outcome, with spontaneous regression at one end of the spectrum and severe disease and death at the other end. Features associated with frequent recurrence, a poor prognosis, and high tumor stage are loss of heterozygosity in the distal region of chromosome 1p and amplification of the N-myc gene. Patched 2 is a novel homologue to the tumor suppressor gene Patched 1, and has been mapped to 1p32-34, a part of chromosome 1 frequently deleted in high stage neuroblastoma tumors. RT-PCR analysis of 9 neuroblastoma cell lines showed expression of both Patched 1 and 2. We analyzed 14, mainly high stage, neuroblastoma tumors for mutations in the Patched 2 gene with denaturing HPLC using the Wave DNA fragment analysis system. In four tumor samples variations were detected within the coding sequence, and two of them gave rise to amino-acid substitutions. These variations were, however, also detected in normal DNA from the respective patients. We conclude that Patched 2 is expressed, but not frequently mutated, in high stage neuroblastomas and is therefore not likely to be involved in the genesis of this tumor.
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| 4. |
- Markevych, I., et al.
(författare)
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Residential greenspace and lung function decline over 20 years in a prospective cohort: The ECRHS study
- 2023
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 178
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Tidskriftsartikel (refereegranskat)abstract
- Background: The few studies that have examined associations between greenspace and lung function in adulthood have yielded conflicting results and none have examined whether the rate of lung function decline is affected.Objective: We explored the association between residential greenspace and change in lung function over 20 years in 5559 adults from 22 centers in 11 countries participating in the population-based, international European Community Respiratory Health Survey.Methods: Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured by spirometry when participants were approximately 35 (1990-1994), 44 (1999-2003), and 55 (2010-2014) years old. Greenness was assessed as the mean Normalized Difference Vegetation Index (NDVI) in 500 m, 300 m, and 100 m circular buffers around the residential addresses at the time of lung function measurement. Green spaces were defined as the presence of agricultural, natural, or urban green spaces in a circular 300 m buffer. Associations of these greenspace parameters with the rate of lung function change were assessed using adjusted linear mixed effects regression models with random intercepts for subjects nested within centers. Sensitivity analyses considered air pollution exposures.Results: A 0.2-increase (average interquartile range) in NDVI in the 500 m buffer was consistently associated with a faster decline in FVC (-1.25 mL/year [95% confidence interval:-2.18 to-0.33]). These associations were especially pronounced in females and those living in areas with low PM10 levels. We found no consistent asso-ciations with FEV1 and the FEV1/FVC ratio. Residing near forests or urban green spaces was associated with a faster decline in FEV1, while agricultural land and forests were related to a greater decline in FVC. Conclusions: More residential greenspace was not associated with better lung function in middle-aged European adults. Instead, we observed slight but consistent declines in lung function parameters. The potentially detri-mental association requires verification in future studies.
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| 5. |
- Zaigham, S, et al.
(författare)
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An observational analysis on the influence of parental allergic rhinitis, asthma and smoking on exhaled nitric oxide in offspring.
- 2024
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Ingår i: Nitric oxide. - 1089-8603 .- 1089-8611.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Parental allergic diseases and smoking influence respiratory disease in the offspring but it is not known whether they influence fractional exhaled nitric oxide (FeNO) in the offspring. We investigated whether parental allergic diseases, parental smoking and FeNO levels in parents were associated with FeNO levels in their offspring.METHODS: We studied 609 offspring aged 16-47 years from the Respiratory Health in Northern Europe, Spain and Australia generation (RHINESSA) study with parental information from the Respiratory Health in Northern Europe (RHINE) III study and the European Community Respiratory Health Survey (ECRHS) III. Linear regression models were used to assess the association between offspring FeNO and parental FeNO, allergic rhinitis, asthma and smoking, while adjusting for potential confounding factors.RESULTS: Parental allergic rhinitis was significantly associated with higher FeNO in the offspring, both on the paternal and maternal side (percent change: 20.3% [95%CI 5.0-37.7], p=0.008, and 13.8% [0.4-28.9], p=0.043, respectively). Parental allergic rhinitis with asthma in any parent was also significantly associated with higher offspring FeNO (16.2% [0.9-33.9], p=0.037). However, parental asthma alone and smoking were not associated with offspring FeNO. Parental FeNO was not associated with offspring FeNO after full adjustments for offspring and parental factors.CONCLUSIONS: Parental allergic rhinitis but not parental asthma was associated with higher levels of FeNO in offspring. These findings suggest that parental allergic rhinitis status should be considered when interpreting FeNO levels in offspring beyond childhood.
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| 6. |
- Zaigham, S, et al.
(författare)
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An observational analysis on the influence of parental allergic rhinitis, asthma and smoking on exhaled nitric oxide in offspring.
- 2024
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Ingår i: Nitric oxide. - 1089-8603 .- 1089-8611. ; 149, s. 60-66
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Parental allergic diseases and smoking influence respiratory disease in the offspring but it is not known whether they influence fractional exhaled nitric oxide (FeNO) in the offspring. We investigated whether parental allergic diseases, parental smoking and FeNO levels in parents were associated with FeNO levels in their offspring.METHODS: We studied 609 offspring aged 16-47 years from the Respiratory Health in Northern Europe, Spain and Australia generation (RHINESSA) study with parental information from the Respiratory Health in Northern Europe (RHINE) III study and the European Community Respiratory Health Survey (ECRHS) III. Linear regression models were used to assess the association between offspring FeNO and parental FeNO, allergic rhinitis, asthma and smoking, while adjusting for potential confounding factors.RESULTS: Parental allergic rhinitis was significantly associated with higher FeNO in the offspring, both on the paternal and maternal side (percent change: 20.3 % [95%CI 5.0-37.7], p = 0.008, and 13.8 % [0.4-28.9], p = 0.043, respectively). Parental allergic rhinitis with asthma in any parent was also significantly associated with higher offspring FeNO (16.2 % [0.9-33.9], p = 0.037). However, parental asthma alone and smoking were not associated with offspring FeNO. Parental FeNO was not associated with offspring FeNO after full adjustments for offspring and parental factors.CONCLUSIONS: Parental allergic rhinitis but not parental asthma was associated with higher levels of FeNO in offspring. These findings suggest that parental allergic rhinitis status should be considered when interpreting FeNO levels in offspring beyond childhood.
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| 7. |
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| 8. |
- Gomez Real, F., et al.
(författare)
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Hormone replacement therapy, body mass index and asthma in perimenopausal women: a cross sectional survey
- 2006
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Ingår i: Thorax.. ; 61:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hormone replacement therapy (HRT) and obesity both appear to increase the risk of asthma. A study was undertaken to investigate the association of HRT with asthma and hay fever in a population of perimenopausal women, focusing on a possible interaction with body mass index (BMI). METHODS: A postal questionnaire was sent to population based samples in Denmark, Estonia, Iceland, Norway, and Sweden in 1999-2001, and 8588 women aged 25-54 years responded (77%). Pregnant women, women using oral contraceptives, and women <46 years were excluded. Analyses included 2206 women aged 46-54 years of which 884 were menopausal and 540 used HRT. Stratified analyses by BMI in tertiles were performed. RESULTS: HRT was associated with an increased risk for asthma (OR 1.57 (95% CI 1.07 to 2.30)), wheeze (OR 1.60 (95% CI 1.22 to 2.10)), and hay fever (OR 1.48 (95% CI 1.15 to 1.90)). The associations with asthma and wheeze were significantly stronger among women with BMI in the lower tertile (asthma OR 2.41 (95% CI 1.21 to 4.77); wheeze OR 2.04 (95% CI 1.23 to 3.36)) than in heavier women (asthma: p(interaction) = 0.030; wheeze: p(interaction) = 0.042). Increasing BMI was associated with more asthma (OR 1.08 (95% CI 1.05 to 1.12) per kg/m(2)). This effect was only found in women not taking HRT (OR 1.10 (95% CI 1.05 to 1.14) per kg/m(2)); no such association was detected in HRT users (OR 1.00 (95% CI 0.92 to 1.08) per kg/m(2)) (p(interaction) = 0.046). Menopause was not significantly associated with asthma, wheeze, or hay fever. CONCLUSIONS: In perimenopausal women there is an interaction between HRT and BMI in the effects on asthma. Lean women who were HRT users had as high a risk for asthma as overweight women not taking HRT. It is suggested that HRT and overweight increase the risk of asthma through partly common pathways.
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| 9. |
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| 10. |
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| 11. |
- Janson, C., et al.
(författare)
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Insomnia is more common among subjects living in damp buildings
- 2005
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Ingår i: Occup Environ Med. ; 62:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Insomnia is a condition with a high prevalence and a great impact on quality of life. Little is known about the relation between and sleep disturbances and the home environment. AIM: To analyse the association between insomnia and building dampness. METHODS: In a cross-sectional, multicentre, population study, 16 190 subjects (mean age 40 years, 53% women) were studied from Reykjavik in Iceland, Bergen in Norway, Umea, Uppsala, and Goteborg in Sweden, Aarhus in Denmark, and Tartu in Estonia. Symptoms related to insomnia were assessed by questionnaire. RESULTS: Subjects living in houses with reported signs of building dampness (n = 2873) had a higher prevalence of insomnia (29.4 v 23.6%; crude odds ratio 1.35, 95% CI 1.23 to 1.48). The association between insomnia and different indicators of building dampness was strongest for floor dampness: "bubbles or discoloration on plastic floor covering or discoloration of parquet floor" (crude odds ratio 1.96, 95% CI 1.66 to 2.32). The associations remained significant after adjusting for possible confounders such as sex, age, smoking history, housing, body mass index, and respiratory diseases. There was no significant difference between the centres in the association between insomnia and building dampness. CONCLUSION: Insomnia is more common in subjects living in damp buildings. This indicates that avoiding dampness in building constructions and improving ventilation in homes may possibly have a positive effect on the quality of sleep.
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| 12. |
- Janson, Christer, et al.
(författare)
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The effect of infectious burden on the prevalence of atopy and respiratory allergies in Iceland, Estonia, and Sweden
- 2007
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 120:3, s. 673-679
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiologic reports on the effect of microbe exposure on the development of atopy and allergic asthma are inconsistent. Objectives: The study investigates the association between serologic markers of infections and occurrence of atopy, allergic asthma, and rhinitis among adults in Iceland, Sweden, and Estonia. Methods: Individuals (n = 1249; mean age, 42 years) from Iceland, Sweden, and Estonia underwent a structured interview and blood sampling. Specific IgE was measured against 4 allergens, and IgG antibodies were measured against Helicobacter pylori, Toxoplasmosis gondii, hepatitis A virus, herpes simplex virus 1, Chlamydia pneumoniae, EBV, and cytomegalovirus. Results: Nonatopic subjects more often had positive serology for Helicobacter pylori, herpes simplex virus 1, Chlamydia pneumoniae, and cytomegalovirus. Having a low number (≤3) of IgG antibodies against the various infectious agents was an independent risk factor for atopy (odds ratio [OR], 1.43; 95% CI, 1.06-1.93), allergic asthma (OR, 1.82; 95% CI, 1.12-2.98), and allergic rhinitis (OR, 1.69; 95% CI, 1.21-2.37). The proportion of atopy that can be explained by a lower number (≤3) of infections was 6.7% in Iceland, 9.2% in Estonia, and 16.4% in Sweden, and 6.7%, 48.2%, and 33.4% for allergic asthma, respectively. Conclusion: Our data are consistent with cumulative protective effect of infections against atopy and respiratory allergies irrespective of route of infection. Clinical implications: The study indicates what microbes or combination of microbes play a role in the complex interplay between hygiene and allergy and may contribute toward the understanding of the allergy epidemic.Background: Epidemiologic reports on the effect of microbe exposure on the development of atopy and allergic asthma are inconsistent. Objectives: The study investigates the association between serologic markers of infections and occurrence of atopy, allergic asthma, and rhinitis among adults in Iceland, Sweden, and Estonia. Methods: Individuals (n = 1249; mean age, 42 years) from Iceland, Sweden, and Estonia underwent a structured interview and blood sampling. Specific IgE was measured against 4 allergens, and IgG antibodies were measured against Helicobacter pylori, Toxoplasmosis gondii, hepatitis A virus, herpes simplex virus 1, Chlamydia pneumoniae, EBV, and cytomegalovirus. Results: Nonatopic subjects more often had positive serology for Helicobacter pylori, herpes simplex virus 1, Chlamydia pneumoniae, and cytomegalovirus. Having a low number (≤3) of IgG antibodies against the various infectious agents was an independent risk factor for atopy (odds ratio [OR], 1.43; 95% CI, 1.06-1.93), allergic asthma (OR, 1.82; 95% CI, 1.12-2.98), and allergic rhinitis (OR, 1.69; 95% CI, 1.21-2.37). The proportion of atopy that can be explained by a lower number (≤3) of infections was 6.7% in Iceland, 9.2% in Estonia, and 16.4% in Sweden, and 6.7%, 48.2%, and 33.4% for allergic asthma, respectively. Conclusion: Our data are consistent with cumulative protective effect of infections against atopy and respiratory allergies irrespective of route of infection. Clinical implications: The study indicates what microbes or combination of microbes play a role in the complex interplay between hygiene and allergy and may contribute toward the understanding of the allergy epidemic.
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| 13. |
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| 14. |
- Jögi, Annika, et al.
(författare)
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Systemic administration of anti-urokinase plasminogen activator receptor monoclonal antibodies induces hepatic fibrin deposition in tissue-type plasminogen activator deficient mice
- 2007
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 5:9, s. 1936-1944
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Degradation of extracellular matrix proteins, such as fibrin, is pivotal to tumor invasion. Inhibition of the interaction between urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and hence pro-u-PA activation, is an attractive approach to anti-invasive cancer therapy. A number of inhibitors exist for the human system, but because of species specificity none of these are efficient in mice. We have recently generated an inhibitory monoclonal antibody (mAb) against mouse u-PAR (mR1) by immunization of u-PAR-deficient mice. OBJECTIVES: To evaluate the effect of mR1 in vivo in a physiological setting sensitive to deregulated fibrinolysis, we have administered mR1 systemically and quantitated the effect on liver fibrin accumulation. METHODS: Wild-type and tissue-type plasminogen activator (t-PA) deficient mice were administered with mR1, or control antibody, during 6 weeks. Thereafter, the livers were retrieved and the amount of liver fibrin measured by unbiased morphometrical analysis of immunofluorescence signal. RESULTS: Systemic administration of mR1 caused significantly increased fibrin signal in anti-u-PAR treated t-PA-deficient mice compared to mock-treated, which mimics the phenotype of u-PAR;t-PA double-deficient mice. Fibrin and fibronectin accumulated within the sinusoidal space and was infiltrated by inflammatory cells. Analysis of small and rare hepatic fibrin plaques observed in t-PA-deficient mice showed infiltrating macrophages that, contrary to surrounding Kuppfer cells, expressed u-PAR. CONCLUSION: We show that u-PAR-expressing macrophages are involved in cell-mediated fibrinolysis of liver fibrin deposits, and that the antimouse-u-PAR mAb is effective in vivo and thus suited for studies of the effect of targeting the u-PA/u-PAR interaction in mouse cancer models.
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| 15. |
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| 16. |
- Moitra, S., et al.
(författare)
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Long-term effect of asthma on the development of obesity among adults: an international cohort study, ECRHS
- 2023
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 78:2, s. 128-135
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Obesity is a known risk factor for asthma. Although some evidence showed asthma causing obesity in children, the link between asthma and obesity has not been investigated in adults. Methods We used data from the European Community Respiratory Health Survey (ECRHS), a cohort study in 11 European countries and Australia in 3 waves between 1990 and 2014, at intervals of approximately 10 years. We considered two study periods: from ECRHS I (t) to ECRHS II (t+1), and from ECRHS II (t) to ECRHS III (t+1). We excluded obese (body mass index >= 30 kg/m(2)) individuals at visit t. The relative risk (RR) of obesity at t+1 associated with asthma at t was estimated by multivariable modified Poisson regression (lag) with repeated measurements. Additionally, we examined the association of atopy and asthma medication on the development of obesity. Results We included 7576 participants in the period ECRHS I-II (51.5% female, mean (SD) age of 34 (7) years) and 4976 in ECRHS II-III (51.3% female, 42 (8) years). 9% of participants became obese in ECRHS I-II and 15% in ECRHS II-III. The risk of developing obesity was higher among asthmatics than non-asthmatics (RR 1.22, 95% CI 1.07 to 1.38), and particularly higher among non-atopic than atopic (1.47; 1.17 to 1.86 vs 1.04; 0.86 to 1.27), those with longer disease duration (1.32; 1.10 to 1.59 in >20 years vs 1.12; 0.87 to 1.43 in <= 20 years) and those on oral corticosteroids (1.99; 1.26 to 3.15 vs 1.15; 1.03 to 1.28). Physical activity was not a mediator of this association. Conclusion This is the first study showing that adult asthmatics have a higher risk of developing obesity than non-asthmatics, particularly those non-atopic, of longer disease duration or on oral corticosteroids.
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| 17. |
- Morgan, Alexandra R, et al.
(författare)
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Feasibility assessment of using oxygen-enhanced magnetic resonance imaging for evaluating the effect of pharmacological treatment in COPD.
- 2014
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Ingår i: European Journal of Radiology. - : Elsevier BV. - 1872-7727 .- 0720-048X. ; 83:11, s. 2093-2101
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Tidskriftsartikel (refereegranskat)abstract
- Oxygen-enhanced MRI (OE-MRI) biomarkers have potential value in assessment of COPD, but need further evaluation before treatment-induced changes can be interpreted. The objective was to evaluate how OE-MRI parameters of regional ventilation and oxygen uptake respond to standard pharmacological interventions in COPD, and how the response compares to that of gold standard pulmonary function tests.
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| 18. |
- Ossenkoppele, Rik, et al.
(författare)
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Amyloid and tau PET-positive cognitively unimpaired individuals are at high risk for future cognitive decline
- 2022
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 28:11, s. 2381-2387
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Tidskriftsartikel (refereegranskat)abstract
- A major unanswered question in the dementia field is whether cognitively unimpaired individuals who harbor both Alzheimer's disease neuropathological hallmarks (that is, amyloid-β plaques and tau neurofibrillary tangles) can preserve their cognition over time or are destined to decline. In this large multicenter amyloid and tau positron emission tomography (PET) study (n = 1,325), we examined the risk for future progression to mild cognitive impairment and the rate of cognitive decline over time among cognitively unimpaired individuals who were amyloid PET-positive (A+) and tau PET-positive (T+) in the medial temporal lobe (A+TMTL+) and/or in the temporal neocortex (A+TNEO-T+) and compared them with A+T- and A-T- groups. Cox proportional-hazards models showed a substantially increased risk for progression to mild cognitive impairment in the A+TNEO-T+ (hazard ratio (HR) = 19.2, 95% confidence interval (CI) = 10.9-33.7), A+TMTL+ (HR = 14.6, 95% CI = 8.1-26.4) and A+T- (HR = 2.4, 95% CI = 1.4-4.3) groups versus the A-T- (reference) group. Both A+TMTL+ (HR = 6.0, 95% CI = 3.4-10.6) and A+TNEO-T+ (HR = 7.9, 95% CI = 4.7-13.5) groups also showed faster clinical progression to mild cognitive impairment than the A+T- group. Linear mixed-effect models indicated that the A+TNEO-T+ (β = -0.056 ± 0.005, T = -11.55, P < 0.001), A+TMTL+ (β = -0.024 ± 0.005, T = -4.72, P < 0.001) and A+T- (β = -0.008 ± 0.002, T = -3.46, P < 0.001) groups showed significantly faster longitudinal global cognitive decline compared to the A-T- (reference) group (all P < 0.001). Both A+TNEO-T+ (P < 0.001) and A+TMTL+ (P = 0.002) groups also progressed faster than the A+T- group. In summary, evidence of advanced Alzheimer's disease pathological changes provided by a combination of abnormal amyloid and tau PET examinations is strongly associated with short-term (that is, 3-5 years) cognitive decline in cognitively unimpaired individuals and is therefore of high clinical relevance.
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| 19. |
- Pass, Jesper, et al.
(författare)
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Murine monoclonal antibodies against murine uPA receptor produced in gene-deficient mice: inhibitory effects on receptor-mediated uPA activity in vitro and in vivo
- 2007
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 97:6, s. 1013-1022
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Tidskriftsartikel (refereegranskat)abstract
- Binding of urokinase plasminogen activator (uPA) to its cellular receptor, uPAR, potentiates plasminogen activation and localizes it to the cell surface. Focal plasminogen activation is involved in both normal and pathological tissue remodeling processes including cancer invasion. The interaction between uPA and uPAR therefore represents a potential target for anti-invasive cancer therapy. Inhibitors of the human uPA-uPAR interaction have no effect in the murine system. To enable in-vivo studies in murine cancer models we have now generated murine monoclonal antibodies (mAbs) against murine uPAR (muPAR) by immunizing uPAR-deficient mice with recombinant muPAR and screened for antibodies, which inhibit the muPA-muPAR interaction. Two of the twelve mAbs obtained, mR1 and mR2, interfered with the interaction between muPAR and the amino-terminal fragment of muPA (mATF) when analyzed by surface plasmon resonance. The epitope for mR1 is located on domain I of muPAR, while that of mR2 is on domains (II-III). In cell binding experiments using radiolabelled mATF, the maximal inhibition obtained with mR1 was 85% while that obtained with mR2 was 50%. The IC(50) value for mR1 was 0.67 nM compared to 0.14 nM for mATF. In an assay based on modified anthrax toxins, requiring cell-bound muPA activity for its cytotoxity, an approximately 50% rescue of the cells could be obtained by addition of mR1. Importantly, in-vivo efficacy of mR1 was demonstrated by the ability of mR1 to rescue mice treated with a lethal dose of uPA-activatable anthrax toxins.
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| 20. |
- Påhlman, Sven, et al.
(författare)
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Differential HIF-1α and HIF-2α Expression in Mammary Epithelial Cells during Fat Pad Invasion, Lactation, and Involution.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- The development and functional cycle of the mammary gland involves a number of processes that are caricatured by breast cancer cells during invasion and metastasis. Expression of the hypoxia-inducible transcription factors HIF-1 and HIF-2 has been associated with metastatic, poor prognosis, and high-grade breast cancers. Since hypoxia affects normal epithelial differentiation, we hypothesise that HIFs are important for normal breast epithelial development and regeneration as well as cancer initiation and progression. Here, we investigated the expression of the oxygen-sensitive HIF-alpha subunits during mouse mammary gland development, lactation, and involution. In breast epithelial cells, HIF-1α was expressed during early development, prior to cell polarisation. In contrast, expression of HIF-2α occurred later and was restricted to a subpopulation of luminal epithelial cells in the lactating gland. Mammary gland involution is a developmental stage that involves extensive tissue remodelling with cell death but survival of tissue stem/progenitor cells. At this stage, HIF-2α, but little HIF-1α, was expressed in CK14-positive epithelial cells. The temporal but differential expression of the HIF-alpha subunits during the mammary gland life cycle indicates that their expression is controlled by additional factors to hypoxia. Further functional studies of the roles of these proteins in the mammary gland and breast cancer are warranted.
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| 21. |
- Svanes, C., et al.
(författare)
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Father's environment before conception and asthma risk in his children: a multi-generation analysis of the Respiratory Health In Northern Europe study
- 2017
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 46:1, s. 235-245
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Tidskriftsartikel (refereegranskat)abstract
- Background: Whereas it is generally accepted that maternal environment plays a key role in child health, emerging evidence suggests that paternal environment before conception also impacts child health. We aimed to investigate the association between children's asthma risk and parental smoking and welding exposures prior to conception. Methods: In a longitudinal, multi-country study, parents of 24 168 offspring aged 2-51 years provided information on their life-course smoking habits, occupational exposure to welding and metal fumes, and offspring's asthma before/after age 10 years and hay fever. Logistic regressions investigated the relevant associations controlled for age, study centre, parental characteristics (age, asthma, education) and clustering by family. Results: Non-allergic early-onset asthma (asthma without hay fever, present in 5.8%) was more common in the offspring with fathers who smoked before conception {odds ratio [OR] = 1.68 [95% confidence interval (CI) = 1.18-2.41]}, whereas mothers' smoking before conception did not predict offspring asthma. The risk was highest if father started smoking before age 15 years [3.24 (1.67-6.27)], even if he stopped more than 5 years before conception [2.68 (1.17-6.13)]. Fathers' pre-conception welding was independently associated with non-allergic asthma in his offspring [1.80 (1.29-2.50)]. There was no effect if the father started welding or smoking after birth. The associations were consistent across countries. Conclusions: Environmental exposures in young men appear to influence the respiratory health of their offspring born many years later. Influences during susceptible stages of spermatocyte development might be important and needs further investigation in humans. We hypothesize that protecting young men from harmful exposures may lead to improved respiratory health in future generations.
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| 22. |
- Thjodleifsson, Bjarni, et al.
(författare)
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Seroprevalence of Helicobacter pylori and cagA antibodies in Iceland, Estonia and Sweden
- 2007
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 39:8, s. 683-689
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Tidskriftsartikel (refereegranskat)abstract
- The public health implications from H. pylori infection are considerable but the transmission routes are largely unknown. In this study, the prevalence, patient characteristics and risk factors for Helicobacter pylori infection were comparatively investigated in Iceland, Sweden and Estonia. Blood samples were collected from 1046 subjects aged≈25-50 y (447 in Reykjavik, 359 in Uppsala and 240 in Tartu) for determination of antibodies to H. pylori and its cagA protein. The prevalence of H. pylori antibodies was 69% in Tartu, 36% in Reykjavik and 11% in Uppsala (p<0.0001). There was an increase in prevalence with age in Iceland and Sweden but not in Estonia. The prevalence of antibodies to the cagA protein in subjects seroreactive to H. pylori was lower in Reykjavik (36%) than in Uppsala (69%) and Tartu (62%) (p<0.0001). H. pylori infection, as determined by seroreactivity, was positively associated with smoking and BMI. Overall, socioeconomic development during the childhood period seems to be the most important factor for the prevalence of H. pylori infection. In adults, smoking may be a contributory factor.
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