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D Andersson

Publications and source records attributed to D Andersson.

At least 19 recordsLinked to original sources
PubMed2005

Diffusive solvent dynamics in a polymer gel electrolyte studied by quasielastic neutron scattering.

A quasielastic neutron scattering study has been performed on a polymer gel electrolyte consisting of lithium perchlorate dissolved in ethylene carbonate/propylene carbonate and stabilized with poly(methyl methacrylate). The dynamics of the solvent, which is crucial for the ion conduction in this system, was probed using the hydrogen/deuterium contrast variation method with nondeuterated solvent and a deuterated polymer matrix. Two relaxation processes of the solvent were studied in the 10-400 microeV range at different temperatures. From analysis of the momentum transfer dependence of the processes we conclude that the faster process ( approximately 100 microeV) is related to rotational diffusion of the solvent and the slower process ( approximately 10 microeV) to translational diffusion of the solvent. The translational diffusion is found to be similar to the diffusion in the corresponding liquid electrolyte at short distances, but geometrically constrained by the polymer matrix at distances beyond approximately 5 A. The study indicates that the hindered diffusion of the solvent on a length scale of the polymer network interchain distance ( approximately 5-20 A) is sufficient to explain the reduced macroscopic diffusivity and ion conductivity of the gel electrolyte compared to the liquid electrolyte.

Journal Article↗
PubMed2005

Cost-effectiveness of acarbose for the management of impaired glucose tolerance in Sweden.

We assessed the cost-effectiveness of acarbose in the management of patients with impaired glucose tolerance (IGT) in Sweden, based on progression to type 2 diabetes (T2D) and cardiovascular (CV) events reported in the STOP-NIDDM trial population, including high-risk subgroups. The cost per patient free from T2D was SEK28,000 or SEK1260 per diabetes free month prior to progression to T2D. The cost per patient free from CV events was SEK101,000 or SEK5000 per CV event free month. For the high CV risk subgroups, acarbose treatment dominated placebo (i.e. acarbose was more effective, less costly). Acarbose significantly reduces the incidence of diabetes and CV events in IGT patients. We predict this may translate into healthcare cost savings that partially or, in patients at high CV risk, fully offset the cost of acarbose. We conclude that acarbose is likely to be cost-effective in the management of impaired glucose tolerance.

Acarbose↗
PubMed2004

Structural investigations of polymer electrolyte poly(propylene oxide)-LiClO4 using diffraction experiments and reverse Monte Carlo simulation.

The structure of an amorphous polymer electrolyte, poly(propylene oxide) (PPO) complexed with LiClO4, has been studied using reverse Monte Carlo (RMC) simulations. The simulations require no force field but are based on experimental data only, in this case from x-ray and neutron diffraction experiments. Excellent agreement between the experimental data and the structures resulting from the RMC simulation is obtained. Samples with ether-oxygen to lithium concentrations (molar ratios) O:Li=16:1 and 5:1 were studied and compared to results of pure PPO from a previous study. We focus on the effects of the solvated salt on the structure of the polymer matrix, the spatial distribution of ions, and the correlations between the anions and the polymer chains. Analyzing the structures produced in the simulations, we find that for a concentration 16:1, the interchain distance is approximately the same as in pure PPO but more well defined. For a concentration 5:1, we find a larger and less well-defined interchain distance compared to the 16:1 concentration. This signifies that at the 16:1 salt concentration, there is enough free volume in the polymer host to accommodate the ions, and that the solvation of salt induces ordering of the polymer matrix. At the higher salt concentration 5:1, the polymer network must expand and become less ordered to host the ions. We also note, in accordance with previous studies, that the solvation of salt changes the conformation of the polymer chain towards more gauche states. The simulations furthermore reveal marked correlations between the polymer chains and the anions, which we suggest arise predominantly from an interaction mediated via cations, which can simultaneously coordinate both ether oxygens in the polymer chains and anions. Interanionic distances at 5 A, which are consistent with two or more anions being coordinated around the same cation, are also observed. On a larger scale, the RMC structure of PPO-LiClO4 16:1 clearly indicates the presence of salt-rich and salt-depleted domains having a length scale of <20 A. In view of such a heterogeneous structure of PPO-LiClO4 16:1, it is plausible that the increased ordering of the polymer matrix is due to rather well-defined structural arrangements within the salt-rich domains, and that the characteristic interchain distance in the salt-rich domains is similar to that of the pure polymer.

Journal Article↗
PubMed2001

Cofactor-induced refolding: refolding of molten globule carbonic anhydrase induced by Zn(II) and Co(II).

The stability versus unfolding to the molten globule intermediate of bovine carbonic anhydrase II (BCA II) in guanidine hydrochloride (GuHCl) was found to depend on the metal ion cofactor [Zn(II) or Co(II)], and the apoenzyme was observed to be least stable. Therefore, it was possible to find a denaturant concentration (1.2 M GuHCl) at which refolding from the molten globule to the native state could be initiated merely by adding the metal ion to the apo molten globule. Thus, refolding could be performed without changing the concentration of the denaturant. The molten globule intermediate of BCA II could still bind the metal cofactor. Cofactor-effected refolding from the molten globule to the native state can be summarized as follows: (1) initially, the metal ion binds to the molten globule; (2) compaction of the metal-binding site region is then induced by the metal ion binding; (3) a functioning active center is formed; and (4) finally, the native tertiary structure is generated in the outer parts of the protein.

Anilino Naphthalenesulfonates↗
PubMed2001

Contribution of tryptophan residues to the CD spectrum of the extracellular domain of human tissue factor: application in folding studies and prediction of secondary structure.

The contribution to the circular dichroism (CD) spectrum made by each of the four Trp residues in the extracellular domain of human tissue factor, sTF (s designates soluble), was determined from difference CD spectra. The individual Trp CD spectra showed that all four residues contributed to the CD spectrum in almost the entire wavelength region investigated (180-305 nm). The sum of the individual spectra of each Trp residue in the near-UV region was qualitatively identical to the wild-type spectrum, clearly demonstrating that the Trp residues are the major contributors to the spectrum in this wavelength region. Trp CD bands interfere with the peptide bands in the far-UV region, leading to uncertainty in the predictions of the amounts of various types of secondary structure. Accordingly, the best prediction of secondary sTF structure content was achieved using a hypothetical Trp-free CD spectrum obtained after subtraction of all individual Trp spectra from the wild-type spectrum. The mutated Trp residues were also exploited as intrinsic probes to monitor the formation of local native-like tertiary structure by kinetic near-UV CD measurements. The global folding reaction was followed in parallel with a novel functional assay that registered the recovery of cofactor activity, i.e. stimulation of the amidolytic activity of Factor VIIa. From these measurements, it was found that sTF appears to regain FVIIa cofactor activity before the final side-chain packing of the Trp residues. The combined kinetic refolding results suggest that the compact asymmetric environments of the individual Trp residues in sTF are formed simultaneously, leading to the conclusion that the native tertiary structure of the whole protein is formed in a cooperative manner.

Circular Dichroism↗
PubMed2001

Tonsillotomy in children with tonsillar hypertrophy.

Tonsillectomy is one of the most frequent surgical procedures carried out on children. Obstructive sleep apnea syndrome, caused by tonsillar hypertrophy, has been attracting increasing interest and tonsillectomy is often performed as a result of this indication. Regardless of the indication, the main aim of tonsillectomy has always been to remove the tonsils completely. The present study was undertaken in order to investigate the effect of two different surgical techniques, tonsillectomy and tonsillotomy, on clinical symptoms in children with symptoms of obstructive sleep apnea syndrome due to tonsillar hypertophy. The study was conducted as a prospective, randomized trial comparing the clinical effects of standard tonsillectomy and tonsillotomy using a CO2 laser. Forty-three children aged 2-9 years were included. Both groups of patients experienced comparable relief from symptoms of snoring and apneas at follow-up after 3 months and 2 years. There was no significant statistical difference between the two groups of patients in terms of both short- and long-term effects on clinical symptoms. Tonsillotomy caused no measurable bleeding during surgery. Postoperative pain and distress were less pronounced in the tonsillotomy group according to visual analog scale evaluations made by patients, parents and nursing staff. In conclusion tonsillotomy appears to be the less traumatic surgical method in cases of upper airway obstruction in children caused by tonsillar hypertrophy.

Child↗
PubMed2000

[Gynecologists about lesbian women--an interview study. There is a risk that lesbian women receive worse treatment].

Lesbian women as patients have reported a lack of professionalism and knowledge in medical care. This interview study focused on the gynecologist in consultation with lesbians, and included questions regarding the gynecologists' knowledge as well as feelings about lesbians and their health-related issues. The study's main conclusion is that gynecologists do not ask about their patient's sexual identity/behavior. They thereby risk offering misleading advice or inadequate treatment.

Attitude of Health Personnel↗
PubMed1999

Structural mapping of an aggregation nucleation site in a molten globule intermediate.

Protein aggregation plays an important role in biotechnology and also causes numerous diseases. Human carbonic anhydrase II is a suitable model protein for studying the mechanism of aggregation. We found that a molten globule state of the enzyme formed aggregates. The intermolecular interactions involved in aggregate formation were localized in a direct way by measuring excimer formation between each of 20 site-specific pyrene-labeled cysteine mutants. The contact area of the aggregated protein was very specific, and all sites included in the intermolecular interactions were located in the large beta-sheet of the protein, within a limited region between the central beta-strands 4 and 7. This substructure is very hydrophobic, which underlines the importance of hydrophobic interactions between specific beta-sheet containing regions in aggregate formation.

Carbonic Anhydrases↗
PubMed1998

[Prevention of acute intermittent porphyria is the best solution. Most important are early diagnosis and counseling].

Recent mapping of acute intermittent porphyria (AIP) in Sweden has confirmed its very high prevalence in northern districts, though about fifty per cent of the gene carriers are to be found in the central and southern parts of the country. More than eighteen different AIP mutations are currently recognised in the Swedish kindreds. One mutations, evidently originating in northern Sweden, is predominant. As AIP is a pharmacogenetic disease, more than 200 substances being currently known to precipitate the neuropsychiatric symptoms, the greatest care is required in prescribing drugs to carriers of genetic predisposition to the disease. Guidelines are provided in the booklet. Drugs contraindicated in acute porphyria (Läkemedel farliga vid akut porfyri), jointly issued by the Swedish Porphyria Association and the Corporation of Swedish Pharmacists (Apoteksbolaget). Where doubt exists, specialists should be consulted since there are a number of factors that may contribute to an adverse reaction. Early diagnosis, preferably before puberty, and counselling are the cornerstones of management, and genetic analysis the diagnostic tool of choice, applicable in most families. In the symptomatic phase, glucose or haem arginate is effective in reversing the metabolic processes responsible for the exacerbation. Recently, the hepatic and late renal manifestations of the disease have been recognised, and early detection of the associated conditions is recommended. This includes monitoring for paraneoplastic prodromes of hepatocellular cancer.

Genetic Counseling↗
PubMed1998

Recurrent Pseudomonas bronchopneumonia and other symptoms as in cystic fibrosis in a child with type I pseudohypoaldosteronism.

We report a child with multiple target organ pseudohypoaldosteronism type 1 with frequent recurrent pulmonary infections caused by Pseudomonas aeruginosa and Pasteurella multocida and high levels of chloride in sweat, urine and nasal secretion. Repetitive faecal chymotrypsin samples have all shown pathological values in spite of no other sign of exocrine pancreas dysfunction. The similarities with cystic fibrosis and the importance of the salt content in bronchial fluid are discussed.

Bronchopneumonia↗
PubMed1997

Formation of local native-like tertiary structures in the slow refolding reaction of human carbonic anhydrase II as monitored by circular dichroism on tryptophan mutants.

In the present study, near-UV CD kinetic measurements on mutants, in which one Trp residue had been replaced, were performed to probe the development of asymmetric environments around specific Trp residues during the refolding of human carbonic anhydrase II (HCAII). In addition, the formation of the active site was probed by the binding of a fluorescent sulfonamide inhibitor. The development of the individual Trp CD spectra during refolding was obtained by subtracting the CD spectrum of the mutant lacking one Trp from that of HCAII at different time points. The same method was used for the particular Trp residues to obtain the kinetic CD traces monitored at a specific wavelength (270 nm). Trp residues 16, 97, and 245 were analyzed. Trp16 probes the N-terminal domain (amino acid residues 1-25), and this part is forming its tertiary structure slower than the major domain (amino acid residues 26-260) of the protein molecule, which contains the active site and a dominating beta-sheet. An essentially native structure of the major domain seems to act as a template for the correct folding of the N terminus. Trp97 is located in a hydrophobic cluster comprising beta-strands 3-5 in the protein core. Previously, we have shown that this region is remarkably stable and compact, and stopped-flow fluorescence data indicate that Trp97 is buried in an apolar compact cluster within a few milliseconds [Svensson, M., Jonasson, P., Freskgård, P.-O., Jonsson, B.-H., Lindgren, M., Martensson, L.-G., Gentile, M., Bóren, K., & Carlsson, U. (1995) Biochemistry 34, 8606-8620; Jonasson, P., Aronsson, G., Carlsson, U., & Jonsson, B.-H. (1997) Biochemistry 36 (in press)]. Here it is shown that the development of the native tertiary structure at Trp97 occurs in the minute time domain. Trp245 is located in a long loop between the N-terminal domain and the core structure. Although this Trp has attained native-like fluorescence properties within the dead time of the CD experiment, it assumes a native-like asymmetric environment even slower than Trp97. Thus, the investigated Trp residues develop their native CD bands at different rates, showing that formation of native-like tertiary structure is occurring with varying rates in different regions of the protein.

Binding Sites↗
PubMed1997

Subunit interaction in extracellular superoxide dismutase: effects of mutations in the N-terminal domain.

Human extracellular superoxide dismutase (hEC-SOD) is a secreted tetrameric protein involved in protection against oxygen free radicals. Because EC-SOD is too large a protein for structural determination by multidimensional NMR, and attempts to crystallize the protein for X-ray structural determination have failed, the three-dimensional structure of hEC-SOD is unknown. This means that alternative strategies for structural studies are needed. The N-terminal domain of EC-SOD has already been studied using the fusion protein FusNN, comprised of the 49 N-terminal amino acids from hEC-SOD fused to human carbonic anhydrase (HCAII). The N-terminal domain in this fusion protein forms a well-defined three-dimensional structure, which probably contains alpha-helical elements and is responsible for the tetramerization of the protein. In this work, we have extended the studies, using site-directed mutagenesis in combination with size-exclusion chromatography, CD, and fluorescence spectroscopy, to investigate the nature of the tetrameric interaction. Our results show that the hydrophobic side of a predicted amphiphatic alpha-helix (formed by residues 14-32) in the N-terminal domain is essential for the subunit interaction.

Amino Acid Sequence↗
PubMed1997

Cost and utilisation of pharmaceuticals in Sweden.

Issues of efficiency, access, equity and cost have informed Swedish national policy toward pharmaceuticals for many years. While retail pharmacies have been owned and operated by a single state company since 1971, the manufacturing of pharmaceuticals has remained privately owned and operated. Costs to the health care system for pharmaceuticals have been rising 4-8% in the last several years, despite greater use of generic substitutes. Beyond price-reduction pressures created by the state retail monopoly, by reference pricing, by positive lists, and by an expanded system of capped patient copayments, the national government is considering plans to decentralise responsibility for all outpatients as well as inpatient drug expenditures to the 26 country councils.

Cost Control↗
PubMed1997

Effects of administration of antioxidants in acute intermittent porphyria.

In order to elucidate the question of free radical involvement in acute porphyric crisis, antioxidants were administered to two acute intermittent porphyria patients with long-standing recurrent attacks. Clinical condition and urinary excretion of porphyrins and porphyrin precursors were monitored before, during and after an eight week therapy with daily doses of vitamin E, beta-carotene, ascorbic acid, selenium, vitamin Q, acetylcysteine, mannitol and carnitine. Blood cell trace element profiles were followed. The administration of the compound antioxidant formula was found not to further impair the clinical or biochemical conditions of the patients but the incidence of the recurrent crises or the severity of the symptoms were not positively affected. Aberrant blood cell trace element profiles with increased granulocyte manganese were normalized during treatment, on cessation of the therapy again resuming the abnormal pretreatment patterns, which may suggest an origin in oxidative stress. No correlation was observed between the concentration of granulocyte manganese and the excretion of 5-aminolaevulinic acid. Indications for participation of this porphyrin precursor in a radical generating process leading to generalized mitochondrial superoxide dismutase induction, as conceivably signalled by increased intracellular manganese, were thus not obtained. The failure to note a clinical response to antioxidant therapy may be due to factors dependent upon dosage of, or interaction between, the antioxidant compounds given, or on restricted bioavailability of the antioxidants at critical anatomical sites, and does not per se invalidate the model of acute porphyria as a hyperoxidative condition.

Adult↗