| 51. |
- Tunbäck, Petra, 1965, et al.
(författare)
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Glycoprotein G of herpes simplex virus type 1: identification of type-specific epitopes by human antibodies.
- 2000
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Ingår i: The Journal of general virology. - 0022-1317. ; 81:Pt 4, s. 1033-40
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Tidskriftsartikel (refereegranskat)abstract
- Serological diagnosis of herpes simplex virus (HSV) infections requires assays based on antigens that expose type-specific determinants. This study was designed to outline the B-cell epitopes of the type-specific glycoprotein G-1 (gG-1) of HSV type 1 (HSV-1), by investigating the reactivity of human anti-gG-1 antibodies, purified from 21 HSV-1-isolation-proven patient sera, to cellulose-bound synthetic peptides spanning the entire gG-1 sequence. The epitope mapping demonstrated that these antibodies bound preferentially to antigenic determinants that localized to regions with a high degree of amino acid similarity to the corresponding glycoprotein in HSV-2, gG-2. In spite of this, the purified anti-gG-1 antibodies were found to be non-reactive to native gG-2 antigen, as well as to overlapping gG-2 peptides, thus supporting the role of gG-1 as a prototype HSV-1 type-specific antigen. One immunodominant region, delimited by amino acids 112-127, reacted with all purified anti-gG-1 antibodies and may be of interest for the further development of a peptide-based HSV-1 type-specific seroassay.
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| 52. |
- Tunbäck, Petra, 1965, et al.
(författare)
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Prevalence of herpes simplex virus antibodies in childhood and adolescence: a cross-sectional study.
- 2003
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Ingår i: Scandinavian journal of infectious diseases. - 0036-5548. ; 35:8, s. 498-502
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Tidskriftsartikel (refereegranskat)abstract
- The changing spectrum of herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infections makes it important to define the seroepidemiology of HSV. The object of this study was to determine the prevalence of HSV-1 and HSV-2 immunoglobulin G antibodies in a young Swedish population by investigating 2106 serum samples from people aged 0-19 y. Sera were tested in HSV type-specific enzyme-linked immunosorbent assays using glycoprotein G-1 (gG-1) and glycoprotein G-2 (gG-2) as antigens. The overall seroprevalence was 31% (95% CI 29-33) for HSV-1 and 0.5% (95% CI 0.2-0.9) for HSV-2. The HSV-1 seroprevalence was higher with increasing age, and significantly higher in the age cohort 15-19 y compared with 1-4-y-olds (37% vs 24%). The HSV-1 infection seemed to be acquired early in life. In the age cohort 1-2 y, the prevalence was over 20%, presumably reflecting an established viral infection. In adolescence the HSV-1 seroprevalence may reflect both oral and sexual transmission. The seroprevalence in the oldest age cohort did not differ significantly from that seen in a Swedish study in which sera were sampled from young girls in the 1970s.
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| 53. |
- Tunbäck, Petra, 1965, et al.
(författare)
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Type-specific reactivity of anti-glycoprotein G antibodies from herpes simplex virus-infected individuals is maintained by single or dual type-specific residues.
- 2005
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 86:Pt 2, s. 247-51
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Forskningsöversikt (refereegranskat)abstract
- Glycoprotein G-1 (gG-1) of herpes simplex virus type 1 (HSV-1) and gG-2 of HSV-2 are the only known HSV proteins that induce type-specific human antibody responses. Recently, it was shown that purified human anti-gG-1 and anti-gG-2 antibodies presented a type-specific reactivity to immunogenic stretches with high similarity between gG-1 and gG-2. In this study, the molecular basis for this type-specific recognition was investigated employing synthetic peptides covering the indicated regions, including substitutions of the type-specific residues. The results revealed that single or dual type-specific residues localized within regions of high similarity could induce significant structural differences, explaining the type-specific recognition of the human antibody response to the gG proteins.
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| 54. |
- Um-Bergström, Petra
(författare)
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From youth to adult : studies on chronic airway obstruction with special reference to events in the neonatal period
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: In western countries, 6-12% of all pregnancies end preterm, i.e. before 37 weeks of gestation. After the introduction of antenatal corticosteroids and improvements of neonatal intensive care, survival rates for children born preterm have increased worldwide. In Sweden, 80% of infants born extremely preterm, i.e. before 28 weeks of gestation, survive. There is, however, an association between preterm birth and later sequelae. Pulmonary complications, such as bronchopulmonary dysplasia (BPD), may result in lung function impairment later in life. It has also been demonstrated that a significant proportion, around 20-25%, of patients with chronic obstructive pulmonary disease (COPD) have never smoked, suggesting other risk factors for developing chronic airway obstruction in adulthood. As there are now more survivors reaching adult life, individuals born preterm are expected to be an increasing group of patients in the future, contributing to the non- smoking proportion of patients with COPD. The overall aim of this thesis was therefore to extensively characterise clinical, functional and mechanistic aspects of pulmonary outcomes in adolescence and in adult age in individuals born preterm with and without BPD. Patients and methods: Individuals born before 32 weeks of gestation between 1992 and 1998 in Stockholm County were investigated both in adolescence (n= 51) and at adult age (n= 49). Half of the individuals born preterm had a diagnosis of BPD. In adult age two control groups of patients with allergic asthma (n= 23) and healthy individuals (n=24) were included. Information on perinatal data, medical history and health related quality of life (HRQoL) was collected. Lung function was measured using dynamic spirometry, body plethysmography diffusing capacity for carbon monoxide (DLCO), impulse oscillometry (IOS) and lung clearance index (LCI) for ventilation inhomogeneity. Bronchoscopy was performed in adults (mean age 20.0 years) including sampling of the large (bronchial wash), and small airways (bronchoalveolar lavage, BAL). Results: Both adolescents and adults with BPD demonstrated airway obstruction in contrast to individuals born preterm without BPD, but both groups had more airway hyper- responsiveness compared to healthy controls. In adulthood, the preterm group had lower DLCO irrespective of BPD status, but only those with BPD had signs of inhomogeneous ventilation. Adults with BPD reported fewer physical symptoms than asthmatic controls, despite lower lung function in the former group. Both preterm groups reported lower scores in the mental component summary of a questionnaire compared to healthy controls. In contrast to the asthmatic group, no eosinophilic inflammation was seen in the preterm group. In BAL, the preterm BPD group showed an increased proportion of activated cytotoxic T cells (CD8+), a decreased proportion of T helper cells (CD4+), and, as a consequence, a decreased CD4/CD8 ratio, when compared to the healthy controls. T-cell subsets in BAL correlated with measures of airflow limitation in individuals with BPD. Further, in bronchial wash, elevated proportion of lymphocytes was observed. A correlationof lymphocyte count with measures of airflow obstruction in the preterm born individuals was seen predominantly in males. Conclusions: Individuals born preterm with a history of BPD have obstructive airflow limitations engaging the small airways. Lymphocytes may have a sex-specific role, as an increased amount was found in the large airways in males with BPD. The increased proportion of cytotoxic (CD8+) T cells in BAL resemble features of COPD, and are compatible with the hypothesis that T-cells may play a mechanistic role in development of airway obstruction in adults with a history of BPD. 5
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| 55. |
- Um-Bergström, Petra, et al.
(författare)
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Lung function development after preterm birth in relation to severity of Bronchopulmonary dysplasia
- 2017
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Ingår i: BMC Pulmonary Medicine. - : BIOMED CENTRAL LTD. - 1471-2466. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bronchopulmonary dysplasia (BPD) is a strong risk factor for respiratory morbidity in children born preterm. Our aims were to evaluate lung function in adolescents born preterm with and without a history of BPD, and to assess lung function change over time from school age.Methods: Fifty-one individuals born in Stockholm, Sweden between gestational ages 24 to 31 weeks (23 neonatally diagnosed with respiratory distress syndrome (RDS) but not BPD, and 28 graded as mild (n = 17), moderate (n = 7) or severe (n = 4) BPD) were examined in adolescence (13-17 years of age) using spirometry, impulse oscillometry (IOS), plethysmography, and ergospirometry. Comparison with lung function data from school age (6-8 years of age) was also performed.Results: Adolescents with a history of BPD had lower forced expiratory volume in 1 s (FEV1) compared to those without BPD (-0.61 vs.-0.02 z-scores, P < 0.05), with lower FEV1 values significantly associated with BPD severity (P for trend 0.002). Subjects with severe BPD had higher frequency dependence of resistance, R5-20, (P < 0.001 vs. non-BPD subjects) which is an IOS indicator of peripheral airway involvement. Between school age and adolescence, FEV1/FVC z-scores decreased in all groups and particularly in the severe BPD group (from -1.68 z-scores at 6-8 years to -2.74 z-scores at 13-17 years, p < 0.05 compared to the non-BPD group).Conclusions: Our results of spirometry and IOS measures in the BPD groups compared to the non-BPD group suggest airway obstruction including involvement of peripheral airways. The longitudinal result of a decrease in FEV1/FVC in the group with severe BPD might implicate a route towards chronic airway obstruction in adulthood.
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| 56. |
- von Otter, Malin, 1978, et al.
(författare)
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Association of Nrf2-encoding NFE2L2 haplotypes with Parkinson's disease.
- 2010
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Ingår i: BMC medical genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Oxidative stress is heavily implicated in the pathogenic process of Parkinson's disease. Varying capacity to detoxify radical oxygen species through induction of phase II antioxidant enzymes in substantia nigra may influence disease risk. Here, we hypothesize that variation in NFE2L2 and KEAP1, the genes encoding the two major regulators of the phase II response, may affect the risk of Parkinson's disease. METHODS: The study included a Swedish discovery case-control material (165 cases and 190 controls) and a Polish replication case-control material (192 cases and 192 controls). Eight tag single nucleotide polymorphisms representing the variation in NFE2L2 and three representing the variation in KEAP1 were chosen using HapMap data and were genotyped using TaqMan Allelic Discrimination. RESULTS: We identified a protective NFE2L2 haplotype in both of our European case-control materials. Each haplotype allele was associated with five years later age at onset of the disease (p = 0.001) in the Swedish material, and decreased risk of PD (p = 2 x 10(-6)), with an odds ratio of 0.4 (95% CI 0.3-0.6) for heterozygous and 0.2 (95% CI 0.1-0.4) for homozygous carriers, in the Polish material. The identified haplotype includes a functional promoter haplotype previously associated with high transcriptional activity. Genetic variation in KEAP1 did not show any associations. CONCLUSION: These data suggest that variation in NFE2L2 modifies the Parkinson's disease process and provide another link between oxidative stress and neurodegeneration.
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| 57. |
- von Otter, Malin, 1978, et al.
(författare)
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Genetic associations of Nrf2-encoding NFE2L2 variants with Parkinson's disease: a multicenter study
- 2014
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 15:1, s. artikel nr 131-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The transcription factor Nrf2, encoded by the NFE2L2 gene, is an important regulator of the cellular protection against oxidative stress. Parkinson s disease is a neurodegenerative disease highly associated with oxidative stress. In a previously published study, we reported associations of NFE2L2 haplotypes with risk and age at onset of idiopathic Parkinson s disease in a Swedish discovery material and a Polish replication material. Here, we have extended the replication study and performed meta-analyses including the Polish material and four new independent European patient-control materials. Furthermore, all SNPs included in the haplotype windows were investigated individually for associations with Parkinson s disease in meta-analyses including all six materials.Methods: Totally 1038 patients and 1600 control subjects were studied. Based on previous NFE2L2 haplotype associations with Parkinson s disease, five NFE2L2 tag SNPs were genotyped by allelic discrimination and three functional NFE2L2 promoter SNPs were genotyped by sequencing. The impact of individual SNPs and haplotypes on risk and age at onset of Parkinson s disease were investigated in each material individually and in meta-analyses of the obtained results.Results: Meta-analyses of NFE2L2 haplotypes showed association of haplotype GAGCAAAA, including the fully functional promoter haplotype AGC, with decreased risk (OR = 0.8 per allele, p = 0.012) and delayed onset (+ 1.1 years per allele, p = 0.048) of Parkinson s disease. These results support the previously observed protective effect of this haplotype in the first study. Further, meta-analyses of the SNPs included in the haplotypes revealed four NFE2L2 SNPs associated with age at onset of Parkinson s disease (rs7557529 G > A, -1.0 years per allele, p = 0.042; rs35652124 A > G, -1.1 years per allele, p = 0.045; rs2886161 A > G, -1.2 years per allele, p = 0.021; rs1806649 G > A, + 1.2 years per allele, p = 0.029). One of these (rs35652124) is a functional SNP located in the NFE2L2 promoter. No individual SNP was associated with risk of Parkinson s disease.Conclusion: Our results support the hypothesis that variation in the NFE2L2 gene, encoding a central protein in the cellular protection against oxidative stress, may contribute to the pathogenesis of Parkinson s disease. Functional studies are now needed to explore these results further.
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| 58. |
- von Otter, Malin, 1978, et al.
(författare)
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Nrf2-encoding NFE2L2 haplotypes influence disease progression but not risk in Alzheimer's disease and age-related cataract
- 2010
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Ingår i: Mechanisms of Ageing and Development. - : Elsevier BV. - 0047-6374 .- 1872-6216. ; 131:2, s. 105-110
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) and age-related cataract, disorders characterized by protein aggregation causing late-onset disease, both involve oxidative stress. We hypothesize that common variants of NFE2L2 and KEAP1, the genes encoding the main regulators of the Nrf2 system, an important defence system against oxidative stress, may influence risk of AD and/or age-related cataract. This case-control study combines an AD material (725 cases and 845 controls), and a cataract material (489 cases and 182 controls). Genetic variation in NFE2L2 and KEAP1 was tagged by eight and three tag single nucleotide polymorphisms (SNPs), respectively. Single SNPs and haplotypes were analyzed for associations with disease risk, age parameters, MMSE and AD cerebrospinal fluid biomarkers. NFE2L2 and KEAP1 were not associated with risk of AD or cataract. However, one haplotype allele of NFE2L2 was associated with 2 years earlier age at AD onset (pc 0.013) and 4 years earlier age at surgery for posterior subcapsular cataract (p(c) = 0.019). Another haplotype of NFE2L2 was associated with 4 years later age at surgery for cortical cataract (p(c) = 0.009). Our findings do not support NFE2L2 or KEAP1 as susceptibility genes for AD or cataract. However, common variants of the NFE2L2 gene may affect disease progression, potentially altering clinically recognized disease onset. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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