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- Nyström, Anna-Maja, 1976-
(författare)
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RAS-MAPK syndromes - a Clinical and Molecular Investigation
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The RAS-MAPK syndromes are a group of clinically and genetically related disorders, characterized by cardiac defects, facial dysmorphism, cutaneous abnormalities and neurocognitive impairment. The pathogenesis is dysregulation of the RAS-MAPK pathway, and several genes within the pathway are involved. The present thesis aimed at identifying genetic causes in three of the RAS-MAPK syndromes - Noonan syndrome (NS), cardio-facio-cutaneous syndrome (CFC) and Neurofibromatosis-Noonan syndrome (NFNS) - and at correlating genotype with phenotype. A mutation analysis of six genes associated with the RAS-MAPK syndromes in NS and CFC patients revealed mutations in 10/31 patients. The results suggested more complex genetic overlap and genetic heterogeneity among these syndromes than previously believed. Subsequently, gene dosage imbalances of seven RAS-MAPK-syndrome-related genes were investigated in mutation-negative patients. A multiplex ligation-dependent probe amplification strategy was developed that excluded copy number changes of these genes as a common mechanism in NS. Genetic causes of clinical variability in NS were investigated where an atypical and severe NS patient was described. In addition, multiple café-au-lait (CAL) spots affected the patient and four otherwise healthy family members. Molecular analysis of four candidate genes revealed a previously described de novo PTPN11 mutation and an inherited NF1 variant in the patient. Neither of them explained the CAL spots trait, which consequently represented a distinct entity. The results suggested that the atypical and severe phenotype in the patient could be a consequence of an additive effect. Finally, a family displaying NFNS was investigated clinically and molecularly revealing a novel mutation in the GAP-domain of NF1. Furthermore, the results suggested that other RAS-MAPK-syndrome-related genes are not involved in NFNS. A proposal of prioritizing the GAP-domain of NF1 in NFNS was presented. Conclusively, these studies contribute to further understanding of the RAS-MAPK syndromes and facilitate the diagnostic process and future prognosis prediction.
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- Al-Manasir, Nodar, et al.
(författare)
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Effects of Temperature and pH on the Contraction and Aggregation of Microgels in Aqueous Suspensions
- 2009
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 113:32, s. 11115-11123
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Tidskriftsartikel (refereegranskat)abstract
- Chemically cross-linked poly(N-isopropylacrylamide) (PNIPAM) microgels and PNIPAM with different amounts of acrylic acid groups (PNIPAM-co-PAA) were synthesized and the temperature-induced aggregation behaviors of aqueous suspensions of these microgels were investigated mainly with the aid of dynamic light scattering (DLS) and turbidimetry. The DLS results show that the particles at all conditions shrink at temperatures up to approximately the lower critical solution temperature (LCST), but the relative contraction effect is larger for the microgels without acid groups or for microgels with added anionic surfactant (SDS). A significant depression of the cloud point is found in suspensions of PNIPAM with very low concentrations of SDS. The compression of the microgels cannot be traced from the turbidity results, but rather the values of the turbidity increase in this temperature interval. This phenomenon is discussed in the framework of a theoretical model. At temperatures above LCST, the size of the microgels without attached charged groups in a very dilute suspension is unaffected by temperature, while the charged particles (pH 7 and 11) continue to collapse with increasing temperature over the entire domain. In this temperature range, low-charged particles of higher concentration and particles containing acrylic acid groups at low pH (pH 2) aggregate, and macroscopic phase separation is approached at higher temperatures. This study demonstrates how the stabilization of microgels can be affected by factors such as polymer concentration, addition of ionic surfactant to particles without charged acid groups, amount of charged groups in the polymer, and pH.
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- Andersson-Sköld, Yvonne, 1957-, et al.
(författare)
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Coal tar-containing asphalt : Resource or hazardous waste?
- 2007
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Ingår i: Journal of Industrial Ecology. - : Wiley-Blackwell. - 1088-1980 .- 1530-9290. ; 11:4, s. 99-116
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Tidskriftsartikel (refereegranskat)abstract
- Coal tar was used in Sweden for the production of asphalt and for the drenching of stabilization gravel until 1973. The tar has high concentrations of polycyclic aromatic hydrocarbons (PAH), some of which may be strongly carcinogenic. Approximately 20 million tonnes of tar-containing asphalt is present in the public roads in Sweden. Used asphalt from rebuilding can be classified as hazardous waste according to the Swedish Waste Act. The cost of treating the material removed as hazardous waste can be very high due to the large amount that has to be treated, and the total environmental benefit is unclear. The transport of used asphalt to landfill or combustion will affect other environmental targets. The present project, based on three case studies of road projects in Sweden, evaluates the consequences of four scenarios for handling the material: reuse, landfill, biological treatment, and incineration. The results show that reuse of the coal tar-containing materials in new road construction is the most favorable alternative in terms of cost, material use, land use, energy consumption, and air emissions.
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- Bondeson, Marie-Louise, et al.
(författare)
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Connexin 26 (GJB2) mutations in two Swedish patients with atypical Vohwinkel (mutilating keratoderma plus deafness) and KID syndrome both extensively treated with acitretin
- 2006
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 86:6, s. 503-508
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Tidskriftsartikel (refereegranskat)abstract
- Neuroectodermal syndromes involving the skin and inner ear may be associated with mutations in connexin proteins, which form gap junctions important for intercellular communication. Vohwinkel syndrome (keratodermia mutilans with hearing loss) and keratitis-ichthyosis-deafness (KID) syndrome are rare ectodermal dysplasias associated with dominant mutations in the GJB2 gene encoding connexin 26. We report here two patients, one with KID and one with Vohwinkel syndrome. Both displayed unusual clinical features and responded well to long-term treatment with oral retinoid. Mutation analysis revealed a novel GJB2 mutation p.Gly59Ser in the patient with Vohwinkel syndrome, whereas a recurrent mutation (p.Asp50Asn) was found in the patient with KID syndrome. The clinical features, particularly a proneness to skin cancer in the patient with Vohwinkel syndrome, are discussed in relation to the identified genotypes.
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- Claesson, Anna-Lena, et al.
(författare)
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Two weeks of overfeeding with candy, but not peanuts, increases insulin levels and body weight
- 2009
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Ingår i: SCANDINAVIAN JOURNAL OF CLINICAL and LABORATORY INVESTIGATION. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 69:5, s. 598-605
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study the effects of snacking based on fast acting carbohydrates (candy) or fat and protein (peanuts) in a prospective randomized, parallel intervention study. Methods: Basal metabolic rate (BMR) and cardiovascular risk factors were measured before and after hyper-alimentation by addition of 20 kcal/kg (84 kJ/kg) body weight of either candy or roasted peanuts, to the regular caloric intake, for two weeks in healthy subjects. Eleven men and 14 women completed the randomized study. Results: Energy-intake increased similarly in the groups (candy: +46.1 +/- 35%, peanuts: +46.8 +/- 28%, p = 0.96). Body-weight (candy: from 67.3 +/- 7.6 kg to 68.1 +/- 7.3 kg, p = 0.01, nuts: from 68.7 +/- 6.1 kg to 69.0 +/- 5.7 kg, p = 0.3) and waist circumference increased significantly only in the candy group. At the end of the study LDL cholesterol (candy: 2.6 +/- 0.4 mmol/L, peanuts: 2.1 +/- 0.4 mmol/L, p = 0.005) and ApoB/ApoA-1-ratio (candy: 0.68 +/- 0.16, peanuts: 0.53 +/- 0.11, p = 0.01) were higher in the candy group than in the peanut group. On the other hand, BMR increased only in the peanut group (candy: from 6.657 +/- 1.1 MJ/24 h to 6.762 +/- 1.1 MJ/24 h, p - 0.3, nuts: from 6.896 +/- 0.98 MJ/24 h to 7.256 +/- 1.1 MJ/24 h, p = 0.02). Conclusion: Two weeks of snacking based on peanuts does not cause the same negative metabolic effects as an isocaloric diet in which the snacking is based on short acting carbohydrates in the form of candy in non-obese healthy subjects.
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| 10. |
- Danielsson, Anna, et al.
(författare)
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Attenuation of insulin-stimulated insulin receptor substrate-1 serine 307 phosphorylation in insulin resistance of type 2 diabetes
- 2005
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Ingår i: Journal of biological chemistry. - 0021-9258 .- 1083-351X. ; 280:41, s. 34389-3492
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance is a primary characteristic of type 2 diabetes and likely causally related to the pathogenesis of the disease. It is a result of defects in signal transduction from the cell surface receptor of insulin to target effects. We found that insulin-stimulated phosphorylation of serine 307 (corresponding to serine 302 in the murine sequence) in the immediate downstream mediator protein of the insulin receptor, insulin receptor substrate-1 (IRS1), is required for efficient insulin signaling and that this phosphorylation is attenuated in adipocytes from patients with type 2 diabetes. Inhibition of serine 307 phosphorylation by rapamycin mimicked type 2 diabetes and reduced the sensitivity of IRS1 tyrosine phosphorylation in response to insulin, while stimulation of the phosphorylation by okadaic acid, in cells from patients with type 2 diabetes, rescued cells from insulin resistance. EC50 for insulin-stimulated phosphorylation of serine 307 was about 0.2 nM with a t1/2 of about 2 min. The amount of IRS1 was similar in cells from non-diabetic and diabetic subjects. These findings identify a molecular mechanism for insulin resistance in non-selected patients with type 2 diabetes.
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