| 1. |
|
|
| 2. |
- Carlsson, Per-Inge, 1959-, et al.
(författare)
-
Variabillity in noise susceptibility in a Swedish population : the role of 35delG mutation in the Connexin 26 (GJB2) gene
- 2004
-
Ingår i: Audiological Medicine. - : Informa UK Limited. - 1651-386X .- 1651-3835. ; 2:2, s. 123-130
-
Tidskriftsartikel (refereegranskat)abstract
- Although it seems that genetic factors can influence individual susceptibility to noise, still very little is known about the genes or the mechanisms involved. The connexin 26 (Cx26) (GJB2) gene is of particular interest to study in relation to noise, since the gene encodes the gap junction protein Cx26. Noise has a metabolic and mechanical effect on the inner ear and may, therefore, interfere with gap junction channels. In order to investigate whether abnormally high susceptibility to noise induced hearing loss (NIHL) in humans is associated with the common 35delG mutation in the Cx26 gene, 1200 noise‐exposed workers were investigated in Sweden. Using a selection procedure based on audiometric analysis, noise exposure data and questionnaires, noise‐exposed workers were divided into two categories: noise susceptible and noise resistant. There was a correspondence in noise susceptibility between this noise‐exposed population and the international reference ISO Standard 1999. Blood samples were drawn from 245 highly selected male subjects (103 noise susceptible, 112 noise resistant and 30 randomized cases), and genomic DNA was analysed with respect to the Cx26 35delG mutation. The incidence of 35delG carriers among this cohort was determined by multiplex, allele‐specific PCR. Two of the 245 subjects (0.8% ‐ [95% confidence interval 0.1–2.9]) were found to be heterozygous carriers of the 35delG mutation, while the remaining 243 subjects were all non‐carriers. Both the heterozygous carriers were found in the noise susceptible group. Statistical evaluation of the results demonstrated no significant difference in carrier incidence between the noise susceptible and noise resistant individuals in our Swedish noise‐exposed population. In conclusion, there was no support for a major role of Cx26 35delG mutation in explaining the variability in noise susceptibility in this Swedish population.
|
|
| 3. |
- Johansson, Niklas, et al.
(författare)
-
A Conceptual Model to Assess Use of a New IT-based Service
- 2003
-
Konferensbidrag (refereegranskat)abstract
- Assessing use is of vital importance for organizations selling and using ICT-based (information and communication technology) services. The purpose of this paper is to present a conceptual model to assess individuals use of new ICT-based services. The model consists of three phases; pre-use, test and use. The concepts of utility and quality are discussed in relation to the three phases. Customers assessment of an ICT-based service has implications for organizations when developing new services. A greater knowledge in this field could have implications for managers understanding of the buyer-seller relationship in a context highly influenced by information technology
|
|
| 4. |
|
|
| 5. |
- Matsson, Hans, 1973-
(författare)
-
Studies of the Ribosomal Protein S19 in Erythropoiesis
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ribosomal proteins are components of the ribosome, the protein synthesis machinery. The ribosomal protein S19 gene (RPS19) is mutated in Diamond-Blackfan anemia, DBA, which is a rare congenital anemia with absence or reduction of erythroid precursors in bone marrow. In this thesis, the role of RPS19 in erythropoiesis is investigated.A genetic analysis of RPS19 in 24 DBA cases was performed. Four novel RPS19 mutations were identified with evidence of wide clinical expression of the disease.Due to the clinical overlap in Transient Erythroblastopenia of Childhood, TEC, and DBA, the two diseases may be caused by a common genetic factor. In a study of seven TEC families, all affected shared at least one parental haplotype in the RPS19 gene region. Coding exons of RPS19 were normal for all affected, although mutations in intronic and regulatory sequences are not excluded. This indicates a genetic factor behind TEC and a possible association between RPS19 and TEC. To investigate the role of RPS19 in erythropoiesis in a mammal, we created a mouse model for the targeted disruption of the homologue Rps19 on the C57BL/6J genetic background. Null mutants are embryonic lethal prior to implantation. The Rps19+/- mice, however, are viable with normal development including the hematopoietic system. The Rps19 transcript level in Rps19+/- mice is normal. Accordingly, RPS19 protein levels are similar in Rps19+/- and Rps19+/+ mice. This argues for a transcriptional up-regulation to compensate for the loss of one Rps19 allele. Peripheral blood is normal in Rps19+/- mice also on the FVB/NJ strain which argues against strain-specific effects of the Rps19 disruption. Preliminary results indicate a reduced erythroid proliferation in response to erythropoietin in Rps19+/- mice, suggesting the requirement of both Rps19 alleles for normal erythroid proliferation under stress. This would support a mechanism by which haplo-insufficiency for RPS19 causes DBA.
|
|
| 6. |
- Norgren, Niklas, 1974-
(författare)
-
Neurofilament light as a marker for neurodegenerative diseases
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neurofilaments are the main cytoskeletal constituents in neuronal cells. They are belived to be important for maintaining the structural integrity and calibre of axons and dendrites thereby influencing the conduction velocity of nerve impulses.The neurofilament chains are divided into three groups according to their molecular size, neurofilament light (NF-L), neurofilament medium (NF-M) and neurofilament heavy (NF-H). The neurofilaments are obligate heteropolymers in vivo in which NF-L forms the backbone to which the heavier chains copolymerize to form the 10 nm neurofilament fibre. Different degenerative processes in the brain raise significant interest owing to the increasing mean age in the western world. Such diseases include amyotrophic lateral sclerosis, vascular dementia, frontal lobe dementia, progressive supra-nuclear paralysis, multiple system atrophy, low pressure hydrocephalus, and multiple sclerosis (MS). We have been able to generate six highly specific monoclonal antibodies for NF-L, and four independent epitopes were elucidated using Biacore and V8 protease degradation. Antibody 2:1 and 47:3 were selected components in a two-site ELISA assay for detection of NF-L in body fluids owing to their outstanding abililty to bind the antigen. The assay has a least detectable dose of 60 ng/l and a standard range of 60 to 64 000 ng/l. The assay was validated on its ability to detect changes of NF-L levels in CSF in patients with different neurological diseases. These were cerebral infarction, amyotrophic lateral sclerosis, relapsing remitting MS, extrapyramidal symptoms, and late onset Alzheimer’s disease. All the patient groups displayed significantly elevated NF-L levels as compared to the controls. We also tested the assay’s ability to monitor the amount of axonal breakdown in an animal model of MS. The NF-L levels were found to be elevated in rodents with chronic experimental autoimmune encephalomyelitis, giving a possible tool for monitoring new treatment strategies for axonal protection in MS. When studying a large population based MS material, we found axonal breakdown to be present early in the disease course and the breakdown was observed both in active relapse and clinically stable disease, indicative of ongoing neurodegeneration. NF-L levels were correlated to progression index, that is, high NF-L levels detected early in disease predict a fast progression of the disease. The amount of glial fibrillary acidic protein, a cytoskeletal protein found in astrocytes, was also quantified and was shown to be a good marker for the more progressive MS subtypes, that is, primary progressive and secondary progressive disease, indicating formation of astrocytic scars and activation of astrocytes. The test dealt with in this thesis has the potential to identify the slow chronic degenerative diseases with progressive disappearance of nerve cells and their large myelinated axons. There is a significant need clinically to be able to quantify such types of cell degeneration in relation to the progressive disappearance of nerve functions and to relate these different conditions to treatment regimens, disease progress, and prognosis.
|
|
| 7. |
- Tentler, Dmitry, et al.
(författare)
-
A balanced reciprocal translocation t(5;7)(q14;q32) associated with autistic disorder: molecular analysis of the chromosome 7 breakpoint.
- 2001
-
Ingår i: American Journal of Medical Genetics. - : Wiley. - 0148-7299 .- 1096-8628. ; 105:8, s. 729-736
-
Tidskriftsartikel (refereegranskat)abstract
- Autism is a neuropsychiatric disorder characterized by impairments in social interaction, restricted and stereotypic pattern of interest with onset by 3 years of age. The results of genetic linkage studied for autistic disorder (AD) have suggested a susceptibility locus for the disease on the long arm of chromosome 7. We report a girl with AD and a balanced reciprocal translocation t(5;7)(q14;q32). The mother carries the translocation but do not express the disease. Fluorescent in situ hybridization (FISH) analysis with chromosome 7-specific YAC clones showed that the breakpoint coincides with the candidate region for AD. We identified a PAC clone that spans the translocation breakpoint and the breakpoint was mapped to a 2 kb region. Mutation screening of the genes SSBP and T2R3 located just centromeric to the breakpoint was performed in a set of 29 unrelated autistic sibling pairs who shared at least one chromosome 7 haplotype. We found no sequence variations, which predict amino acid alterations. Two single nucleotide polymorphisms were identified in the T2R3 gene, and associations between allele variants and AD in our population were not found. The methylation pattern of different chromosome 7 regions in the patient's genomic DNA appears normal. Here we report the clinical presentation of the patient with AD and the characterization of the genomic organization across the breakpoint at 7q32. The precise localization of the breakpoint on 7q32 may be relevant for further linkage studies and molecular analysis of AD in this region.
|
|
| 8. |
- Tentler, Dmitry, et al.
(författare)
-
A candidate region for Asperger syndrome defined by two 17p breakpoints
- 2003
-
Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 11:2, s. 189-195
-
Tidskriftsartikel (refereegranskat)abstract
- Asperger syndrome (AS) is a mild form of autistic disorder characterised by impairment in social interaction as well as a restricted pattern of behaviour, interests, and activities. Two patients with AS and balanced translocations t(13;17) and t(17;19), respectively, were identified. Fluorescent in situ hybridisation (FISH) analysis with chromosome 17 specific clones to metaphase chromosomes from both patients showed that the chromosome 17 breakpoints are located within a 300 kb region at 17p13. The region spans 14 known genes. The expression of these genes was analysed in lymphoblastoid RNA derived from the patients and healthy control individuals. The CHRNE, DKFZP566H073, LOC90048, PFN1, SPAG7, KIAA0909, ZNF232 and KIF1C genes showed similar levels of expression in cell lines with the translocations when compared with cell lines with normal karyotype. No expression was detected for the MINK, GP1BA, SLC25A11, ENO3, FLJ10060 and USP6 genes in any of the cell lines. The close physical relation of the two 17p breakpoints suggest a common genetic aetiology for the phenotype in the patients. Structural and functional analysis of the genes located around the two 17p breakpoints in t(13;17) and t(17;19) patients may reveal candidate sequences for the AS phenotype.
|
|
