12 results on '"Aberg V"'
Search Results
2. A comparison of different definitions of growth response in short prepubertal children treated with growth hormone.
- Author
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Bang P, Bjerknes R, Dahlgren J, Dunkel L, Gustafsson J, Juul A, Kriström B, Tapanainen P, and Aberg V
- Subjects
- Biomarkers, Pharmacological analysis, Child, Child, Preschool, Cross-Sectional Studies, Female, Humans, Male, Prognosis, Puberty drug effects, Puberty physiology, Retrospective Studies, Treatment Outcome, Body Height drug effects, Diagnostic Techniques, Endocrine, Growth Disorders diagnosis, Growth Disorders drug therapy, Human Growth Hormone therapeutic use
- Abstract
Background: How to define poor growth response in the management of short growth hormone (GH)-treated children is controversial., Aim: Assess various criteria of poor response., Subjects and Methods: Short GH-treated prepubertal children [n = 456; height (Ht) SD score (SDS) ≤-2] with idiopathic GH deficiency (IGHD, n = 173), idiopathic short stature (ISS, n = 37), small for gestational age (SGA, n = 54), organic GHD (OGHD, n = 40), Turner syndrome (TS, n = 43), skeletal dysplasia (n = 15), other diseases (n = 46) or syndromes (n = 48) were evaluated in this retrospective multicenter study. Median age at GH start was 6.3 years and Ht SDS -3.2., Results: Median [25-75 percentile] first-year gain in Ht SDS was 0.65 (0.40-0.90) and height velocity (HtV) 8.67 (7.51-9.90) cm/year. Almost 50% of IGHD children fulfilled at least one criterion for poor responders. In 28% of IGHD children, Ht SDS gain was <0.5 and they had lower increases in median IGF-I SDS than those with Ht SDS >0.5. Only IGHD patients with peak stimulated growth hormone level <3 μg/l responded better than those with ISS. A higher proportion of children with TS, skeletal dysplasia or born SGA had Ht SDS gain <0.5., Conclusion: Many children respond poorly to GH therapy. Recommendations defining a criterion may help in managing short stature patients., (Copyright © 2011 S. Karger AG, Basel.)
- Published
- 2011
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3. Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation.
- Author
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Cegelski L, Pinkner JS, Hammer ND, Cusumano CK, Hung CS, Chorell E, Aberg V, Walker JN, Seed PC, Almqvist F, Chapman MR, and Hultgren SJ
- Subjects
- Amyloid antagonists & inhibitors, Animals, Bacterial Adhesion drug effects, Bacterial Proteins antagonists & inhibitors, Escherichia coli Infections drug therapy, Escherichia coli Infections microbiology, Escherichia coli K12 growth & development, Escherichia coli K12 metabolism, Escherichia coli K12 pathogenicity, Escherichia coli Proteins antagonists & inhibitors, Mice, Molecular Structure, Small Molecule Libraries chemistry, Small Molecule Libraries therapeutic use, Urinary Tract Infections drug therapy, Urinary Tract Infections microbiology, Uropathogenic Escherichia coli growth & development, Uropathogenic Escherichia coli pathogenicity, Virulence, Amyloid biosynthesis, Bacterial Proteins biosynthesis, Biofilms growth & development, Escherichia coli Proteins biosynthesis, Small Molecule Libraries pharmacology, Uropathogenic Escherichia coli metabolism
- Abstract
Curli are functional extracellular amyloid fibers produced by uropathogenic Escherichia coli (UPEC) and other Enterobacteriaceae. Ring-fused 2-pyridones, such as FN075 and BibC6, inhibited curli biogenesis in UPEC and prevented the in vitro polymerization of the major curli subunit protein CsgA. The curlicides FN075 and BibC6 share a common chemical lineage with other ring-fused 2-pyridones termed pilicides. Pilicides inhibit the assembly of type 1 pili, which are required for pathogenesis during urinary tract infection. Notably, the curlicides retained pilicide activities and inhibited both curli-dependent and type 1-dependent biofilms. Furthermore, pretreatment of UPEC with FN075 significantly attenuated virulence in a mouse model of urinary tract infection. Curli and type 1 pili exhibited exclusive and independent roles in promoting UPEC biofilms, and curli provided a fitness advantage in vivo. Thus, the ability of FN075 to block the biogenesis of both curli and type 1 pili endows unique anti-biofilm and anti-virulence activities on these compounds.
- Published
- 2009
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4. Associations of variable coloration with niche breadth and conservation status among Australian reptiles.
- Author
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Forsman A and Aberg V
- Subjects
- Analysis of Variance, Animals, Australia, Lizards genetics, Pigmentation genetics, Polymorphism, Genetic, Population Dynamics, Snakes genetics, Species Specificity, Conservation of Natural Resources, Ecosystem, Lizards physiology, Pigmentation physiology, Snakes physiology
- Abstract
We evaluate predictions concerning the evolutionary and ecological consequences of color polymorphisms. Previous endeavors have aimed at identifying conditions that promote the evolution and maintenance within populations of alternative variants. But the polymorphic condition may also influence important population processes. We consider the prediction that populations that consist of alternative "ecomorphs" with coadapted gene complexes will utilize more diverse resources and display higher rates of colonization success, population persistence, and range expansions, while being less vulnerable to range contractions and extinctions, compared with monomorphic populations. We perform pairwise comparative analyses based on information for 323 species of Australian lizards and snakes. We find that species with variable color patterns have larger ranges, utilize a greater diversity of habitat types, and are underrepresented among species currently listed as threatened. These results are consistent with the proposition that the co-occurrence of multiple color variants may promote the ecological success of populations and species, but there are also alternative interpretations.
- Published
- 2008
- Full Text
- View/download PDF
5. Pilicides-small molecules targeting bacterial virulence.
- Author
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Aberg V and Almqvist F
- Subjects
- Fimbriae, Bacterial chemistry, Models, Molecular, Molecular Structure, Structure-Activity Relationship, Virulence, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents pharmacology, Drug Design, Fimbriae, Bacterial drug effects, Gram-Negative Bacteria drug effects, Gram-Negative Bacteria metabolism, Gram-Negative Bacteria pathogenicity
- Abstract
In a time of emerging bacterial resistance there is a vital need for new targets and strategies in antibacterial therapy. Using uropathogenic Escherichia coli as a model pathogen we have developed a class of compounds, pilicides, which inhibit the formation of virulence-associated organelles termed pili. The pilicides interfere with a highly conserved bacterial assembly and secretion system called the chaperone-usher pathway, which is abundant in a vast number of Gram-negative pathogens and serves to assemble multi-protein surface fibers (pili/fimbriae). This class of compounds provides a platform to gain insight into important biological processes such as the molecular mechanisms of the chaperone-usher pathway and the sophisticated function of pili. Pili are primarily involved in bacterial adhesion, invasion and persistence to host defenses. On this basis, pilicides can aid the development of new antibacterial agents.
- Published
- 2007
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6. Pilicides regulate pili expression in E. coli without affecting the functional properties of the pilus rod.
- Author
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Aberg V, Fällman E, Axner O, Uhlin BE, Hultgren SJ, and Almqvist F
- Subjects
- Anti-Bacterial Agents chemistry, Blotting, Western, Dose-Response Relationship, Drug, Escherichia coli growth & development, Escherichia coli metabolism, Escherichia coli Proteins metabolism, Fimbriae Proteins metabolism, Fimbriae, Bacterial chemistry, Fimbriae, Bacterial physiology, Microscopy, Atomic Force, Models, Biological, Molecular Chaperones metabolism, Molecular Structure, Naphthalenes chemistry, Optical Tweezers, Periplasmic Proteins metabolism, Porins metabolism, Thiazoles chemistry, Anti-Bacterial Agents pharmacology, Escherichia coli drug effects, Fimbriae, Bacterial drug effects, Naphthalenes pharmacology, Thiazoles pharmacology
- Abstract
The infectious ability of uropathogenic Escherichia coli relies on adhesive fibers, termed pili or fimbriae, that are expressed on the bacterial surface. Pili are multi-protein structures that are formed via a highly preserved assembly and secretion system called the chaperone-usher pathway. We have earlier reported that small synthetic compounds, referred to as pilicides, disrupt both type 1 and P pilus biogenesis in E. coli. In this study, we show that the pilicides do not affect the structure, dynamics or function of the pilus rod. This was demonstrated by first suppressing the expression of P pili in E. coli by pilicide treatment and, next, measuring the biophysical properties of the pilus rod. The reduced abundance of pili was assessed with hemagglutination, atomic force microscopy and Western immunoblot analysis. The biodynamic properties of the pili fibers were determined by optical tweezers force measurements on individual pili and were found to be intact. The presented results establish a potential use of pilicides as chemical tools to study important biological processes e.g. adhesion, pilus biogenesis and the role of pili in infections and biofilm formation.
- Published
- 2007
- Full Text
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7. Rationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria.
- Author
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Pinkner JS, Remaut H, Buelens F, Miller E, Aberg V, Pemberton N, Hedenström M, Larsson A, Seed P, Waksman G, Hultgren SJ, and Almqvist F
- Subjects
- Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Bacterial Adhesion drug effects, Biofilms, Crystallography, X-Ray, Escherichia coli Proteins chemistry, Escherichia coli Proteins genetics, Escherichia coli Proteins metabolism, Fimbriae Proteins genetics, Fimbriae Proteins metabolism, Humans, Models, Molecular, Molecular Chaperones chemistry, Molecular Chaperones genetics, Molecular Chaperones metabolism, Molecular Structure, Periplasmic Proteins chemistry, Periplasmic Proteins genetics, Periplasmic Proteins metabolism, Point Mutation, Protein Conformation, Urinary Bladder cytology, Urinary Bladder microbiology, Virulence Factors genetics, Virulence Factors metabolism, Bridged Bicyclo Compounds chemical synthesis, Bridged Bicyclo Compounds pharmacology, Bridged Bicyclo Compounds therapeutic use, Drug Design, Escherichia coli drug effects, Escherichia coli pathogenicity, Fimbriae, Bacterial drug effects, Fimbriae, Bacterial metabolism, Pyridones chemical synthesis, Pyridones pharmacology, Pyridones therapeutic use, Urinary Tract Infections drug therapy, Urinary Tract Infections microbiology, Virulence Factors antagonists & inhibitors
- Abstract
A chemical synthesis platform with broad applications and flexibility was rationally designed to inhibit biogenesis of adhesive pili assembled by the chaperone-usher pathway in Gram-negative pathogens. The activity of a family of bicyclic 2-pyridones, termed pilicides, was evaluated in two different pilus biogenesis systems in uropathogenic Escherichia coli. Hemagglutination mediated by either type 1 or P pili, adherence to bladder cells, and biofilm formation mediated by type 1 pili were all reduced by approximately 90% in laboratory and clinical E. coli strains. The structure of the pilicide bound to the P pilus chaperone PapD revealed that the pilicide bound to the surface of the chaperone known to interact with the usher, the outer-membrane assembly platform where pili are assembled. Point mutations in the pilicide-binding site dramatically reduced pilus formation but did not block the ability of PapD to bind subunits and mediate their folding. Surface plasmon resonance experiments confirmed that the pilicide interfered with the binding of chaperone-subunit complexes to the usher. These pilicides thus target key virulence factors in pathogenic bacteria and represent a promising proof of concept for developing drugs that function by targeting virulence factors.
- Published
- 2006
- Full Text
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8. NMR studies of interactions between periplasmic chaperones from uropathogenic E. coli and pilicides that interfere with chaperone function and pilus assembly.
- Author
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Hedenström M, Emtenäs H, Pemberton N, Aberg V, Hultgren SJ, Pinkner JS, Tegman V, Almqvist F, Sethson I, and Kihlberg J
- Subjects
- Anti-Bacterial Agents pharmacology, Binding Sites, Escherichia coli cytology, Escherichia coli physiology, Escherichia coli Proteins chemistry, Escherichia coli Proteins metabolism, Fimbriae Proteins chemistry, Fimbriae Proteins metabolism, Fimbriae, Bacterial metabolism, Molecular Chaperones metabolism, Nuclear Magnetic Resonance, Biomolecular methods, Periplasmic Proteins chemistry, Periplasmic Proteins metabolism, Pyridones pharmacology, Tyrosine analogs & derivatives, Tyrosine pharmacology, Anti-Bacterial Agents chemistry, Escherichia coli drug effects, Fimbriae, Bacterial drug effects, Molecular Chaperones chemistry
- Abstract
Adherence of uropathogenic Escherichia coli to host tissue is mediated by pili, which are hair-like protein structures extending from the outer cell membrane of the bacterium. The chaperones FimC and PapD are key components in pilus assembly since they catalyse folding of subunits that are incorporated in type 1 and P pili, respectively, and also transport the subunits across the periplasmic space. Recently, compounds that inhibit pilus biogenesis and interfere with chaperone-subunit interactions have been discovered and termed pilicides. In this paper NMR spectroscopy was used to study the interaction of different pilicides with PapD and FimC in order to gain structural knowledge that would explain the effect that some pilicides have on pilus assembly. First relaxation-edited NMR experiments revealed that the pilicides bound to the PapD chaperone with mM affinity. Then the pilicide-chaperone interaction surface was investigated through chemical shift mapping using 15N-labelled FimC. Principal component analysis performed on the chemical shift perturbation data revealed the presence of three binding sites on the surface of FimC, which interacted with three different classes of pilicides. Analysis of structure-activity relationships suggested that pilicides reduce pilus assembly in E. coli either by binding in the cleft of the chaperone, or by influencing the orientation of the flexible F1-G1 loop, both of which are part of the surface by which the chaperone forms complexes with pilus subunits. It is suggested that binding to either of these sites interferes with folding of the pilus subunits, which occurs during formation of the chaperone-subunit complexes. In addition, pilicides that influence the F1-G1 loop also appear to reduce pilus formation by their ability to dissociate chaperone-subunit complexes.
- Published
- 2005
- Full Text
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9. C-Terminal properties are important for ring-fused 2-pyridones that interfere with the chaperone function in uropathogenic E. coli.
- Author
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Aberg V, Hedenström M, Pinkner JS, Hultgren SJ, and Almqvist F
- Subjects
- Anti-Bacterial Agents pharmacology, Escherichia coli pathogenicity, Escherichia coli Proteins drug effects, Fimbriae, Bacterial drug effects, Hemagglutination, Magnetic Resonance Spectroscopy, Microbial Sensitivity Tests, Periplasmic Proteins drug effects, Structure-Activity Relationship, Anti-Bacterial Agents chemistry, Molecular Chaperones drug effects, Pyridones chemical synthesis, Pyridones pharmacology
- Abstract
Virulence-associated organelles, termed pili or fimbriae, are assembled via the highly conserved chaperone-usher pathway in a vast number of pathogenic bacteria. Substituted bicyclic 2-pyridones, pilicides, inhibit pilus formation, possibly by interfering with the active site residues Arg8 and Lys112 of chaperones in uropathogenic E. coli. In this article we describe the synthesis and evaluation of nine analogues of a biologically active pilicide. Derivatization was performed with respect to its C-terminal features and the affinities for the chaperone PapD were studied with 1H relaxation-edited NMR spectroscopy. It could be concluded that the carboxylic acid functionality and also its spatial location was important for binding. In all cases, binding was significantly reduced or even abolished when the carboxylic acid was replaced by other substituents. In addition, in vivo results from a hemagglutination assay are presented where the derivatives have been evaluated for their ability to inhibit pilus formation in uropathogenic E. coli.
- Published
- 2005
- Full Text
- View/download PDF
10. Microwave-assisted decarboxylation of bicyclic 2-pyridone scaffolds and identification of Abeta-peptide aggregation inhibitors.
- Author
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Aberg V, Norman F, Chorell E, Westermark A, Olofsson A, Sauer-Eriksson AE, and Almqvist F
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- Magnetic Resonance Spectroscopy, Microscopy, Atomic Force, Spectrometry, Mass, Fast Atom Bombardment, Spectrophotometry, Infrared, Amyloid beta-Peptides chemistry, Carboxylic Acids chemistry, Microwaves, Peptides antagonists & inhibitors, Pyridones chemistry
- Abstract
A reagent-free microwave-assisted decarboxylation procedure for carboxylic acid functionalized bicyclic 2-pyridones has been developed. This new method, based on microwave heating at 220 degrees C for 600 seconds in N-methyl pyrrolidone (NMP), proved to be practical and very efficient, resulting in decarboxylated 2-pyridones in near-quantitative yields. The decarboxylated products and the intermediate 2-pyridones in the form of carboxylic acid methyl esters and carboxylic acids were screened for their effect on Abeta-peptide aggregation. Two out of the 21 2-pyridones described in this study inhibited amyloid formation of the Alzheimer Abeta(1-40) peptide. The effect was seen even at a 4 : 1 ratio of 2-pyridone and monomeric Abeta-peptide.
- Published
- 2005
- Full Text
- View/download PDF
11. Microwave-assisted synthesis of highly substituted aminomethylated 2-pyridones.
- Author
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Pemberton N, Aberg V, Almstedt H, Westermark A, and Almqvist F
- Abstract
By employing microwave-assisted organic synthesis (MAOS) efficient conditions to introduce aminomethylene substituents in highly substituted bicyclic 2-pyridones have been established. Primary amino methylene substituents were introduced via a cyanodehalogenation followed by a borane dimethyl sulfide reduction of the afforded nitrile. In both of these transformations, microwave irradiation proved to be superior to traditional conditions and the primary amines were obtained in good overall yields (55-58% over three steps). To incorporate tertiary aminomethylene substituents in the 2-pyridone framework, a microwave-assisted Mannich reaction using preformed iminium salts proved to be effective. Thus highly substituted 2-pyridones were obtained in 48-93% yields.
- Published
- 2004
- Full Text
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12. Myelographic spinal cord diameter and neurological impairment.
- Author
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Gilland O and Stockhaus-Aberg V
- Subjects
- Humans, Myelography, Central Nervous System Diseases diagnosis, Spinal Cord anatomy & histology, Spinal Cord Diseases diagnosis
- Published
- 1965
- Full Text
- View/download PDF
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