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| 2. |
- Carlsson, G, et al.
(author)
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Central nervous system involvement in severe congenital neutropenia : neurological and neuropsychological abnormalities associated with specific HAX1 mutations
- 2008
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 264:4, s. 388-400
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Homozygous mutations in the HAX1 gene were recently identified in severe congenital neutropenia patients belonging to the original Kostmann family in northern Sweden. Our observations suggested that these patients also develop neurological and neuropsychological symptoms. METHODS: Detailed clinical studies and mutation analyses were performed in the surviving patients belonging to the Kostmann kindred and in two patients not related to this family, along with studies of HAX1 splice variant expression in normal human tissues. RESULTS: Five of six Kostmann family patients and one other patient from northern Sweden harboured homozygous HAX1 mutations (568C-->T, Q190X) and one carried a heterozygous ELA2 gene mutation. One Swedish patient of Kurdish extraction carried alternative homozygous HAX1 mutations (131G-->A, W44X). All the three patients with Q190X mutations who were alive and available for evaluation developed neurological disease with decreased cognitive function, and three of four patients who reached 10 years developed epilepsy. In contrast, the patients with the ELA2 and W44X HAX1 mutations, respectively, showed no obvious neurological abnormalities. Moreover, two alternative HAX1 splice variants were identified in normal human tissues, including the brain. Both transcripts contained exon 5, harbouring the Q190X mutation, whereas the 5' end of exon 2 containing the W44X mutation was spliced out from the second transcript. CONCLUSIONS: We describe neurological and neuropsychological abnormalities for the first time in Kostmann disease patients. These central nervous system symptoms appear to be associated with specific HAX1 mutations.
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| 3. |
- Dahlqvist, Johanna, et al.
(author)
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Congenital ichthyosis : mutations in ichthyin are associated with specific structural abnormalities in the granular layer of epidermis
- 2007
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In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 44:10, s. 615-620
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Journal article (peer-reviewed)abstract
- Background: Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of skin disorders. Several mutant genes have been identified in ARCI, but the association between genotype and phenotype is poorly understood. Methods: To investigate genotype–phenotype correlations in ARCI, we selected 27 patients from 18 families with specific ultrastructural features of the epidermis. The characteristic findings using electron microscopy (EM) were abnormal lamellar bodies and elongated membranes in the stratum granulosum, classified as ARCI EM type III. DNA samples from a subset of affected individuals were screened for homozygous genomic regions, and a candidate gene region was identified on chromosome 5q33. The region coincides with the ichthyin gene, previously reported as mutated in ARCI. Results: Mutation screening of ichthyin revealed missense or splice-site mutations in affected members from 16 of 18 (89%) families with characteristics of ARCI EM type III. In a control group of 18 patients with ARCI without EM findings consistent with type III, we identified one patient homozygous for a missense mutation in ichthyin. Discussion: Our findings indicate a strong association between ultrastructural abnormalities in the granular layer of epidermis and ichthyin mutations. The results also suggest that EM provides a tool for specific diagnosis in a genetically homogenous subgroup of patients with ARCI.
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| 4. |
- Amsler, C., et al.
(author)
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Review of particle physics
- 2008
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 667:1-5, s. 1-1
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Research review (peer-reviewed)abstract
- This biennial Review summarizes much of particle physics. Using data from previous editions., plus 2778 new measurements from 645 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We also summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors., probability, and statistics. Among the 108 reviews are many that are new or heavily revised including those on CKM quark-mixing matrix, V-ud & V-us, V-cb & V-ub, top quark, muon anomalous magnetic moment, extra dimensions, particle detectors, cosmic background radiation, dark matter, cosmological parameters, and big bang cosmology.
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| 7. |
- Melin, Malin, et al.
(author)
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A founder mutation for ichthyosis prematurity syndrome restricted to 76 kb by haplotype association
- 2006
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In: Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1434-5161 .- 1435-232X. ; 51:10, s. 864-871
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Journal article (peer-reviewed)abstract
- Autosomal recessive congenital ichthyosis (ARCI) is a group of keratinisation disorders that includes the ichthyosis prematurity syndrome (IPS). IPS is rare and almost exclusively present in a restricted region in the middle of Norway and Sweden, which indicates a founder effect for the disorder. We recently reported linkage of IPS to chromosome 9q34, and we present here the subsequent fine-mapping of this region with known and novel microsatellite markers as well as single nucleotide polymorphisms (SNPs). Allelic association, evaluated with Fisher's exact test and P (excess), was used to refine the IPS haplotype to approximately 1.6 Mb. On the basis of the average length of the haplotype in IPS patients, we calculated the age of a founder mutation to approximately 1,900 years. The IPS haplotype contains a core region of 76 kb consisting of four marker alleles shared by 97.7% of the chromosomes associated with IPS. This region spans four known genes, all of which are expressed in mature epidermal cells. We present the results from the analysis of these four genes and their corresponding transcripts in normal and patient-derived samples.
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| 8. |
- Agnelli, G, et al.
(author)
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Safety assessment of new antithrombotic agents : Lessons from the EXTEND study on ximelagatran.
- 2009
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In: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 123:3, s. 488-497
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Journal article (peer-reviewed)abstract
- BACKGROUND: Ximelagatran, the first oral direct thrombin inhibitor, was shown to be an effective antithrombotic agent but was associated with potential liver toxicity after prolonged administration. OBJECTIVES AND METHODS: The aim of the EXTEND study was to assess safety and efficacy of extended administration (35 days) of ximelagatran or enoxaparin for the prevention of venous thromboembolism after elective hip replacement and hip fracture surgery. A follow-up period, including assessment of liver enzymes (in particular alanine aminotransferase; ALAT), until post-operative day 180 was planned, with visits at days 56 and 180. RESULTS: Randomization and administration of study drugs were stopped following a report of serious liver injury occurring 3 weeks after completion of ximelagatran treatment. At the time of study termination, 1158 patients had been randomized and 641 had completed the 35-day treatment; with 303 ximelagatran and 265 enoxaparin patients remaining in the study through to the day 56 follow-up visit. Overall, 58 patients showed an ALAT increase to >2x upper limit of normal: 31 treated with enoxaparin, 27 with ximelagatran. Three ximelagatran patients also showed symptoms potentially related to liver toxicity. Eleven ximelagatran patients showed an ALAT increase after study treatment ended. The clinical development of ximelagatran was terminated and the drug withdrawn from the market. Evaluation of the relative efficacy of the two treatments as specified in the protocol was impossible due to the premature termination of the study. CONCLUSIONS: Prolonged administration of ximelagatran was associated with an increased risk of liver toxicity. In a substantial proportion of patients, ALAT increase occurred after treatment withdrawal. The findings seen with ximelagatran should be considered when designing studies with new antithrombotic agents.
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| 10. |
- Ardlin, Berit I., et al.
(author)
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Corrosion of dental nickel-aluminum bronze with a minor gold content-mechanism and biological impact
- 2009
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In: Journal of Biomedical Materials Research. Part B - Applied biomaterials. - Malden : Wiley-Blackwell. - 1552-4973 .- 1552-4981. ; 88B:2, s. 465-473
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Journal article (peer-reviewed)abstract
- Objectives: To study corrosion and to evaluate biological effects in vitro of corrosion products of a copper-aluminum-nickel alloy with 2% gold. Methods: The alloy NPGTM+2 with the nominal composition Cu:77.3; Al:7.8; Ni:4.3; Fe:3.0; Zn:2.7; Au:2.0; and Mn:1.7 was characterized. Static immersion in acidic saline, pH 2.2-2.4, was used to determine release of metallic elements in a milieu simulating the condition of plaque build-up in interproximal areas of the tooth. Corrosion and surface reactions in saline and artificial saliva were studied by electrochemical techniques including registration of open-circuit-potentials, polarization curves and impedance spectra. Extracts were made in cell culture media and acidic saline and used for MTT test for cytotoxicity and HET-CAM method for irritation. Results: The mean amount of elements released in the acidic saline were in g cm-2 : Cu:632; Al:210; Ni:144; Fe:122; Zn:48; Mn:52. No protective film was formed on the surface of the alloy, as extensive corrosion was observed in both saline and artificial saliva. The corrosion rate was higher in saline than in artificial saliva. Acidic extracts of the alloy diluted up to 64 times reduced cell viability with 80% or more. The extract induced coagulation of the blood vessels of the CAM and was rated as moderate irritant solution. Significance: The nickel-aluminum bronze showed high corrosion rate caused by an inability to create a protective surface layer. High levels of toxic elements were found after static immersion testing, and the corrosion products had a distinct adverse effect on the biological activity.
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