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1.
  • Bayat, J. T., et al. (författare)
  • Daily life impact of malocclusion in Swedish adolescents: A grounded theory study
  • 2013
  • Ingår i: Acta Odontologica Scandinavica. - 0001-6357 .- 1502-3850. ; 71:3-4, s. 792-798
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To explore how malocclusions affect daily life in adolescents and how adolescents cope with malocclusion-related distress. Materials and methods. Twelve strategically selected teenagers, seven girls and five boys aged 13-14 years, participated in this study. Open, tape-recorded in-depth interviews based on Focus Group Discussions (FGD) were performed using a theme guide and analyzed according to the qualitative method of classic grounded theory (GT). Results. A core category was identified and named 'Repeatedly reminded of the malocclusion'. Associated to the core category, five categories were generated and labeled 'Being directed by the media's ideal image', 'Monitoring others' teeth', 'Struggling with low self-esteem', 'Hiding one's teeth' and 'Striving for cure'. Low self-esteem appeared to be frequently reinforced through the concerns for the malocclusion and handled via different coping strategies, such as hiding the teeth and striving to receive orthodontic treatment. Such processes were further enforced through the influence of media. Low self-esteem could be associated to a visible malposition of teeth, according to the informants. Having to wait for orthodontic treatment was frustrating the adolescents. Conclusions. Adolescents with malocclusion are often reminded of their condition, which can lead to avoiding strategies to minimize the negative feelings associated with the teeth and low self-esteem. Clinicians may therefore need to be aware of potential irrational behaviors when interacting with adolescents with malocclusions. The findings also suggest that there might be a discrepancy of attitudes between professionals focusing on oral health aspects of malocclusions and the adolescents focusing on esthetic aspects.
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2.
  • Hallberg, Lillemor R-M, 1942, et al. (författare)
  • Facing a moral dilemma--introducing a dental care insurance within the public dental service.
  • 2012
  • Ingår i: Swedish dental journal. - : Swedish dental journal. - 0347-9994. ; 36:3, s. 149-56
  • Tidskriftsartikel (refereegranskat)abstract
    • Through the reform entitled "Dental care insurance-dental care at a fixed price", patients are offered a dental insurance, a capitation plan, that ensures that they can visit the dentist regularly during a period of three years at a fixed price per month (Frisktandvård).This insurance may be offered to all patients. The aim of this study was to generate a theory explaining the main concern for the staff at the public dental service when they have to introduce and advocate dental care insurance to patients. Interview data from 17 persons, representing different professions within the public dental service, were collected and analyzed simultaneously in line with guidelines for grounded theory. The results indicated that dentists/dental hygienists experienced several difficult standpoints concerning the implementation of the dental insurance, somewhat of a moral dilemma. The staff generally had a "cautiously positive attitude" to the forthcoming dental care insurance, but had perceptions how and when the patients should be offered the insurance and what that may mean to the clinic.The respondents reflected about the economic aspects for the clinic and how the oral health may be affected over time for the patients.
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3.
  • Andersson, H.O., et al. (författare)
  • Optimization of P1-P3 groups in symmetric and asymmetric HIV-1 protease inhibitors
  • 2003
  • Ingår i: European Journal of Biochemistry. - 0014-2956 .- 1432-1033. ; 270:8, s. 1746-1758
  • Tidskriftsartikel (refereegranskat)abstract
    • HIV-1 protease is an important target for treatment of AIDS, and efficient drugs have been developed. However, the resistance and negative side effects of the current drugs has necessitated the development of new compounds with different binding patterns. In this study, nine C-terminally duplicated HIV-1 protease inhibitors were cocrystallised with the enzyme, the crystal structures analysed at 1.8-2.3 Å resolution, and the inhibitory activity of the compounds characterized in order to evaluate the effects of the individual modifications. These compounds comprise two central hydroxy groups that mimic the geminal hydroxy groups of a cleavage-reaction intermediate. One of the hydroxy groups is located between the d-oxygen atoms of the two catalytic aspartic acid residues, and the other in the gauche position relative to the first. The asymmetric binding of the two central inhibitory hydroxyls induced a small deviation from exact C2 symmetry in the whole enzyme-inhibitor complex. The study shows that the protease molecule could accommodate its structure to different sizes of the P2/P2' groups. The structural alterations were, however, relatively conservative and limited. The binding capacity of the S3/S3' sites was exploited by elongation of the compounds with groups in the P3/P3' positions or by extension of the P1/P1' groups. Furthermore, water molecules were shown to be important binding links between the protease and the inhibitors. This study produced a number of inhibitors with Ki values in the 100 picomolar range.
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4.
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5.
  • Borhade, Sanjay R, et al. (författare)
  • Inhibition of Insulin-Regulated Aminopeptidase (IRAP) by Arylsulfonamides
  • 2014
  • Ingår i: ChemistryOpen. - 2191-1363. ; 3:6, s. 256-263
  • Tidskriftsartikel (refereegranskat)abstract
    • The inhibition of insulin-regulated aminopeptidase (IRAP, EC 3.4.11.3) by angiotenesin IV is known to improve memory and learning in rats. Screening 10 500 low-molecular-weight compounds in an enzyme inhibition assay with IRAP from Chinese Hamster Ovary (CHO) cells provided an arylsulfonamide (N-(3-(1H-tetrazol-5-yl)phenyl)-4-bromo-5-chlorothiophene-2-sulfonamide), comprising a tetrazole in the meta position of the aromatic ring, as a hit. Analogues of this hit were synthesized, and their inhibitory capacities were determined. A small structure-activity relationship study revealed that the sulfonamide function and the tetrazole ring are crucial for IRAP inhibition. The inhibitors exhibited a moderate inhibitory potency with an IC50=1.1±0.5 μm for the best inhibitor in the series. Further optimization of this new class of IRAP inhibitors is required to make them attractive as research tools and as potential cognitive enhancers.
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6.
  • Chetpakdeechit, Woranuch, et al. (författare)
  • Social life aspects of young adults with cleft lip and palate: grounded theory approach.
  • 2009
  • Ingår i: Acta odontologica Scandinavica. - 1502-3850. ; 67:2, s. 122-8
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The findings of many questionnaire and inventory studies suggest that people with cleft lip and/or palate report a decreased quality of life. Common problems include dissatisfaction with the external appearance of the lips and nose, speech problems, depression, and anxiety. This qualitative study aimed to explore the subjective perceptions and values of young adults with clefts, particularly with regard to their social lives. MATERIAL AND METHODS: Twelve persons participated in an in-depth interview. Among those, seven had a repaired isolated cleft palate involving only the hard/soft palate. Five had a repaired bilateral cleft lip and palate that had been a continuous lesion of the lip, the alveolar process, and the palate. A grounded theory approach was used to conduct and analyze the interviews. RESULTS: The study revealed seven important categories--hoping to be like other people, being treated differently from others, experiencing deviation from others, regarding oneself as being different from others, lack of recognition, low self-esteem, and receiving recognition from significant others--with hoping to be like other people as the core category. CONCLUSION: Young adults with either cleft lip and palate or isolated cleft palate who received recognition from significant others reported increased self-esteem and greater ability to cope with their social lives.
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7.
  • Diwakarla, Shanti, et al. (författare)
  • Aryl Sulfonamide Inhibitors of Insulin-Regulated Aminopeptidase Enhance Spine Density in Primary Hippocampal Neuron Cultures
  • 2016
  • Ingår i: ; 7:10, s. 1383-1392
  • Tidskriftsartikel (refereegranskat)abstract
    • The zinc metallopeptidase insulin regulated aminopeptidase (IRAP), which is highly expressed in the hippocampus and other brain regions associated with cognitive function, has been identified as a high-affinity binding site of the hexapeptide angiotensin IV (Ang IV). This hexapeptide is thought to facilitate learning and memory by binding to the catalytic site of IRAP to inhibit its enzymatic activity. In support of this hypothesis, low molecular weight, nonpeptide specific inhibitors of TRAP have been shown to enhance memory in rodent models. Recently, it was demonstrated that linear and macrocyclic Ang IV-derived peptides can alter the shape and increase the number of dendritic spines in hippocampal cultures, properties associated with enhanced cognitive performance. After screening a library of 10 500 drug like substances for their ability to inhibit IRAP, we identified a series of low molecular weight aryl sulfonamides, which exhibit no structural similarity to Ang IV, as moderately potent IRAP inhibitors:A structural and biological characterization of three of these aryl sulfonamides was performed. Their binding modes to human IRAP were explored by docking calculations combined with molecular dynamics simulations and binding affinity estimations using the linear interaction energy method. Two alternative binding modes emerged from this analysis, both of which correctly rank the ligands according to their experimental binding affinities for this series of compounds. Finally, we show that two of these drug-like IRAP inhibitors can alter dendritic spine morphology and increase spine density in primary cultures of hippocampal neurons.
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8.
  • Engen, Karin, et al. (författare)
  • Identification of Drug-Like Inhibitors of Insulin-Regulated Aminopeptidase Through Small-Molecule Screening
  • 2016
  • Ingår i: ; 14:3, s. 180-193
  • Tidskriftsartikel (refereegranskat)abstract
    • Intracerebroventricular injection of angiotensin IV, a ligand of insulin-regulated aminopeptidase (IRAP), has been shown to improve cognitive functions in several animal models. Consequently, IRAP is considered a potential target for treatment of cognitive disorders. To identify nonpeptidic IRAP inhibitors, we adapted an established enzymatic assay based on membrane preparations from Chinese hamster ovary cells and a synthetic peptide-like substrate for high-throughput screening purposes. The 384-well microplate-based absorbance assay was used to screen a diverse set of 10,500 compounds for their inhibitory capacity of IRAP. The assay performance was robust with Z-values ranging from 0.81 to 0.91, and the screen resulted in 23 compounds that displayed greater than 60% inhibition at a compound concentration of 10M. After hit confirmation experiments, purity analysis, and promiscuity investigations, three structurally different compounds were considered particularly interesting as starting points for the development of small-molecule-based IRAP inhibitors. After resynthesis, all three compounds confirmed low M activity and were shown to be rapidly reversible. Additional characterization included activity in a fluorescence-based orthogonal assay and in the presence of a nonionic detergent and a reducing agent, respectively. Importantly, the characterized compounds also showed inhibition of the human ortholog, prompting our further interest in these novel IRAP inhibitors.
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9.
  • Engen, Karin, et al. (författare)
  • Synthesis, Evaluation and Proposed Binding Pose of Substituted Spiro-Oxindole Dihydroquinazolinones as IRAP Inhibitors
  • 2020
  • Ingår i: ChemistryOpen. - 2191-1363. ; 9:3, s. 325-337
  • Tidskriftsartikel (refereegranskat)abstract
    • Insulin‐regulated aminopeptidase (IRAP) is a new potential macromolecular target for drugs aimed for treatment of cognitive disorders. Inhibition of IRAP by angiotensin IV (Ang IV) improves the memory and learning in rats. The majority of the known IRAP inhibitors are peptidic in character and suffer from poor pharmacokinetic properties. Herein, we present a series of small non‐peptide IRAP inhibitors derived from a spiro‐oxindole dihydroquinazolinone screening hit (pIC50 5.8). The compounds were synthesized either by a simple microwave (MW)‐promoted three‐component reaction, or by a two‐step one‐pot procedure. For decoration of the oxindole ring system, rapid MW‐assisted Suzuki‐Miyaura cross‐couplings (1 min) were performed. A small improvement of potency (pIC50 6.6 for the most potent compound) and an increased solubility could be achieved. As deduced from computational modelling and MD simulations it is proposed that the S‐configuration of the spiro‐oxindole dihydroquinazolinones accounts for the inhibition of IRAP.
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10.
  • Hallberg, Jenny, et al. (författare)
  • Interaction between smoking and genetic factors in the development of chronic bronchitis
  • Ingår i: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 177:5, s. 486-490
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: Smoking is a primary risk factor for chronic bronchitis, emphysema, and chronic obstructive pulmonary disease, but since not all smokers develop disease, it has been suggested that some individuals may be more susceptible to exogenous factors, such as smoking, and that this susceptibility could be genetically determined. Objectives: The aim of the present study was to assess, in a population-based sample of twins, the following: (1) to what extent genetic factors contribute to the development of chronic bronchitis, including emphysema, taking sex into consideration, and (2) whether the genetic influences on chronic bronchitis, including emphysema, are separate from those for smoking behavior. Methods: Disease cases and smoking habits were identified in 44,919 twins older than 40 years from the Swedish Twin Registry. Disease was defined as self-reported chronic bronchitis or emphysema, or recurrent cough with phlegm. Individuals who had smoked 10 pack-years or more were defined as smokers. Univariate and bivariate structural equation models were used to estimate the heritability specific for chronic bronchitis and that in common with smoking. Measurements and Main Results: The heritability estimate for chronic bronchitis was a moderate 40% and only 14% of the genetic influences were shared with smoking. Conclusions: Genetic factors independent of those related to smoking habits play a role in the development of chronic bronchitis.
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