| 1. |
- Ayeni, O. R., et al.
(författare)
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Clinical and Radiographic Criteria Define "Acceptable" Surgical Correction of Hip Femoroacetabular Impingement Syndrome as Well as Postoperative Complications: An International Modified Delphi Study
- 2023
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Ingår i: Arthroscopy-the Journal of Arthroscopic and Related Surgery. - : Elsevier BV. - 0749-8063. ; 39:5, s. 1198-1210
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To develop recommendations for clinical and radiographic criteria to help define the "acceptable" surgical correction of femoroacetabular impingement syndrome (FAIS) and identify/define complications postoperatively. Methods: A 3-phase modified Delphi study was conducted involving a case-based survey; a Likert/multiple choice-based survey concerning radiographic and physical examination characteristics to help define FAIS correction, as well as the prevalence and definition of potential postoperative complications; and 2 consensus meetings. Results: Of the 75 experts invited, 54 completed the Phase I survey, 50 completed the Phase II survey (72% and 67% response rate), and 50 participated in the Phase III consensus meetings. For both typical and atypical (complex) cases, there was consensus that fluoroscopy with multiple views and dynamic hip assessment should be used intraoperatively (96% and 100%, respectively). For typical FAIS cases, the Expert Panel agreed that Dunn lateral and anteroposterior radiographs were the most important radiographs to evaluate the hip postoperatively (88%, consensus). When asked about evaluating the correction of cam impingement postoperatively, 87% voted that they use subjective evaluation of the "sphericity" of the femoral head. In the case of focal and global pincer-type FAIS, there was consensus that the reduction or elimination of the crossover sign (84%) and lateral center-edge angle (91%) were important to inform the extent of the FAIS correction. There was consensus for recommending further investigation at 6 months postoperatively if hip pain had increased/plateaued (92% agreed); that additional investigation and treatment should occur between 6 and 12 months (90% agreed); and that a reoperation may be recommended at 12 months or later following this investigation period (89% agreed). Conclusions: This consensus project identified the importance of using fluoroscopy and dynamic hip assessment intraoperatively; Dunn lateral and anteroposterior view radiographs postoperatively; evaluating the "sphericity" of the femoral head for cam-type correction and the use of dynamic hip assessment; reducing/eliminating the crossover sign for focal pincertype FAIS; evaluating the lateral center-edge angle for global pincer-type FAIS; and avoiding overcorrection of pincer-type FAIS. In cases in which postoperative hip pain increased/plateaued, further investigation and treatment is warranted between 6 and 12 months, and a reoperation may be recommended at a minimum of 12 months depending on the cause of the hip pain. Clinical Relevance: Hip arthroscopy surgeons have yet to reach a firm agreement on what constitutes an "acceptable" or "good" surgery radiographically and how they can achieve desired clinical outcomes. Although this was a comprehensive effort, more study is needed to determine therapeutic thresholds that can be universally applied.
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| 2. |
- Hastoy, B., et al.
(författare)
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Electrophysiological properties of human beta-cell lines EndoC-beta H1 and -beta H2 conform with human beta-cells
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Limited access to human islets has prompted the development of human beta cell models. The human beta cell lines EndoC-beta H1 and EndoC-beta H2 are increasingly used by the research community. However, little is known of their electrophysiological and secretory properties. Here, we monitored parameters that constitute the glucose-triggering pathway of insulin release. Both cell lines respond to glucose (6 and 20 mM) with 2- to 3-fold stimulation of insulin secretion which correlated with an elevation of [Ca2+](i), membrane depolarisation and increased action potential firing. Similar to human primary beta cells, K-ATP channel activity is low at 1mM glucose and is further reduced upon increasing glucose concentration; an effect that was mimicked by the K-ATP channel blocker tolbutamide. The upstroke of the action potentials reflects the activation of Ca2+ channels with some small contribution of TTX-sensitive Na+ channels. The repolarisation involves activation of voltage-gated Kv2.2 channels and large-conductance Ca2+-activated K+ channels. Exocytosis presented a similar kinetics to human primary beta cells. The ultrastructure of these cells shows insulin vesicles composed of an electrondense core surrounded by a thin clear halo. We conclude that the EndoC-beta H1 and -beta H2 cells share many features of primary human beta-cells and thus represent a useful experimental model.
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| 3. |
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| 4. |
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| 5. |
- Badiali, Luca, et al.
(författare)
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Adhesion GPCRs are widely expressed throughout the subsections of the gastrointestinal tract
- 2012
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Ingår i: BMC Gastroenterology. - 1471-230X. ; 12, s. 134-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: G protein-coupled receptors (GPCRs) represent one of the largest families of transmembrane receptors and the most common drug target. The Adhesion subfamily is the second largest one of GPCRs and its several members are known to mediate neural development and immune system functioning through cell-cell and cell-matrix interactions. The distribution of these receptors has not been characterized in detail in the gastrointestinal (GI) tract. Here we present the first comprehensive anatomical profiling of mRNA expression of all 30 Adhesion GPCRs in the rat GI tract divided into twelve subsegments.METHODS: Using RT-qPCR, we studied the expression of Adhesion GPCRs in the esophagus, the corpus and antrum of the stomach, the proximal and distal parts of the duodenum, ileum, jejunum and colon, and the cecum.RESULTS: We found that twenty-one Adhesion GPCRs (70%) had a widespread (expressed in five or more segments) or ubiquitous (expressed in eleven or more segments) distribution, seven (23%) were restricted to a few segments of the GI tract and two were not expressed in any segment. Most notably, almost all Group III members were ubiquitously expressed, while the restricted expression was characteristic for the majority of group VII members, hinting at more specific/localized roles for some of these receptors.CONCLUSIONS: Overall, the distribution of Adhesion GPCRs points to their important role in GI tract functioning and defines them as a potentially crucial target for pharmacological interventions.
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| 6. |
- Barauskas, Justas, et al.
(författare)
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Towards redox active liquid crystalline phases of lipids: a monoolein/water system with entrapped derivatives of ferrocene
- 2003
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Ingår i: Chemistry and Physics of Lipids. - 0009-3084. ; 123:1, s. 87-97
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Tidskriftsartikel (refereegranskat)abstract
- The phase and electrochemical behavior of the aqueous mixtures of monoolein (MO) and synthetic ferrocene (Fc) derivatives containing long alkyl chains -(Z)-octadec-9-enoylferrocene (1), (Z)-octadecen-9-ylferrocene (2), and ferrocenylmethyl (Z)-octadec-9-enoate (3)-were studied. At low hydration, the reversed micelles (L-2 phase) and cubic Q(230) phase of MO can accommodate relatively high amounts ( > 6 wt.%) of the Fc-derivative 2, whereas at high hydration, the pseudoternary cubic phase Q(224) is destabilized even at about 2 wt.% of this Fc. Increasing the Fc-derivative content induces L-alpha L-2 and L-alpha --> reversed bicontinuous cubic phase (Q(II)) H-II transitions depending upon hydration. A rough study of the MO system containing compounds I and 3 indicates very similar phase behavior to that of the MO/2/H2O system. Compound 2 apparently has no effect on the lipid monolayer thickness in the pseudoternary L-alpha, H-II and Q(II) liquid crystalline phases of MO. Within a 3D-structure of the Q224 phase, derivatives 1-3 exhibit electrochemical activity on the gold electrode. The one-electron redox conversion processes are electro-chemically quasi-reversible and controlled by diffusion. The values of apparent diffusion coefficient (D-app) and heterogeneous electron-transfer rate constant (k(s)) of Fcs are significantly lo er in the cubic,phase matrix when compared to the acetonitrile solution. By contrast, the MO H-II phase with entrapped Fc-derivatives does not exhibit electrochemical activity on the electrode surface. It is suggested that the diffusional anisotropy and/or localized aggregation of compounds 1-3 within a 2D-structure of the H-II phase account(s) for the latter observation. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
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| 7. |
- Hellstrand, Erik, et al.
(författare)
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Adsorption of α-Synuclein to Supported Lipid Bilayers: Positioning and Role of Electrostatics.
- 2013
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 4:10, s. 1339-1351
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Tidskriftsartikel (refereegranskat)abstract
- An amyloid form of the protein α-synuclein is the major component of the intraneuronal inclusions called Lewy bodies, which are the neuropathological hallmark of Parkinson's disease (PD). α-Synuclein is known to associate with anionic lipid membranes, and interactions between aggregating α-synuclein and cellular membranes are thought to be important for PD pathology. We have studied the molecular determinants for adsorption of monomeric α-synuclein to planar model lipid membranes composed of zwitterionic phosphatidylcholine alone or in a mixture with anionic phosphatidylserine (relevant for plasma membranes) or anionic cardiolipin (relevant for mitochondrial membranes). We studied the adsorption of the protein to supported bilayers, the position of the protein within and outside the bilayer, and structural changes in the model membranes using two complementary techniques-quartz crystal microbalance with dissipation monitoring, and neutron reflectometry. We found that the interaction and adsorbed conformation depend on membrane charge, protein charge, and electrostatic screening. The results imply that α-synuclein adsorbs in the headgroup region of anionic lipid bilayers with extensions into the bulk but does not penetrate deeply into or across the hydrophobic acyl chain region. The adsorption to anionic bilayers leads to a small perturbation of the acyl chain packing that is independent of anionic headgroup identity. We also explored the effect of changing the area per headgroup in the lipid bilayer by comparing model systems with different degrees of acyl chain saturation. An increase in area per lipid headgroup leads to an increase in the level of α-synuclein adsorption with a reduced water content in the acyl chain layer. In conclusion, the association of α-synuclein to membranes and its adsorbed conformation are of electrostatic origin, combined with van der Waals interactions, but with a very weak correlation to the molecular structure of the anionic lipid headgroup. The perturbation of the acyl chain packing upon monomeric protein adsorption favors association with unsaturated phospholipids preferentially found in the neuronal membrane.
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| 8. |
- Herrera-Marschitz, M, et al.
(författare)
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On the origin of extracellular glutamate levels monitored in the basal ganglia of the rat by in vivo microdialysis
- 1996
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 66:4, s. 1726-1735
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Tidskriftsartikel (refereegranskat)abstract
- Several putative neurotransmitters and metabolites were monitored simultaneously in the extracellular space of neostriatum, substantia nigra, and cortex and in subcutaneous tissue of the rat by in vivo microdialysis. Glutamate (Glu) and aspartate (Asp) were at submicromolar and gamma-aminobutyric acid (GABA) was at nanomolar concentrations in all brain regions. The highest concentration of dopamine (DA) was in the neostriatum. Dynorphin B (Dyn B) was in the picomolar range in all brain regions. Although no GABA, DA, or Dyn B could be detected in subcutaneous tissue, Glu and Asp levels were 5 and approximately 5 and approximately 0.4 microM, respectively. Lactate and pyruvate concentrations were approximately 200 and approximately 10 microM in all regions. The following criteria were applied to ascertain the neuronal origin of substances quantified by microdialysis: sensitivity to (a) K+ depolarization, (b) Na+ channel blockade, (c) removal of extracellular Ca2+, and (d) depletion of presynaptic vesicles by local administration of alpha-latrotoxin. DA, Dyn B, and GABA largely satisfied all these criteria. In contrast, Glu and Asp levels were not greatly affected by K+ depolarization and were increased by perfusing with tetrodotoxin or with Ca2+-free medium, arguing against a neuronal origin. However, Glu and Asp, as well as DA and GABA, levels were decreased under both basal and K+-depolarizing conditions by alpha-latrotoxin. Because the effect of K+ depolarization on Glu and Asp could be masked by reuptake into nerve terminals and glial cells, the reuptake blocker dihydrokainic acid (DHKA) or L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) was included in the microdialysis perfusion medium. The effect of K+ depolarization on Glu and Asp levels was increased by DHKA, but GABA levels were also affected. In contrast, PDC increased only Glu levels. It is concluded that there is pool of releasable Glu and Asp in the rat brain. However, extracellular levels of amino acids monitored by in vivo microdialysis reflect the balance between neuronal release and reuptake into surrounding nerve terminals and glial elements.
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| 9. |
- Misiunas, A., et al.
(författare)
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Thermomyces lanuginosus lipase in the liquid-crystalline phases of aqueous phytantriol: X-ray diffraction and vibrational spectroscopic studies
- 2008
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Ingår i: Biophysical Chemistry. - : Elsevier BV. - 1873-4200 .- 0301-4622. ; 134:3, s. 144-156
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Tidskriftsartikel (refereegranskat)abstract
- The influence of Thermomyces lanuginosus lipase (TLL) on the phase behaviour of liquid-crystalline phases of aqueous phytantriol as well as conformational changes of TLL entrapped in the cubic Q(230) phase have been studied by small angle X-ray diffraction (SAXD), FT-Raman, and FT-IR techniques. It was found that the lipidic Q(230) Phase is able to accommodate up to 10 wt.% of TLL, and the temperature of phase transition to the inverted hexagonal phase H-11 increases indicating stabilizing effect of the protein. FT-Raman analysis of Trp amino acid marker band W3 revealed that the average rotation angle around the C-3 - C-beta bond of four TLL residues of TLL in the Q(230) phase increases. Reasoning from available TLL crystallographic data, this result is explained by structural transition of entrapped protein to so-called "open" and more related to the enzymaticallyactive conformation. TLL secondary structure analysis by amide I and amide III vibrational bands showed that content of alpha-helixes does not change, while a part of beta-sheet structures transforms to less ordered elements upon incorporation of protein into the Q230 phase of aqueous phytantriol. (c) 2008 Elsevier B.V. All rights served.
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| 10. |
- Samoshina, Yulia, et al.
(författare)
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Equilibrium aspects of polycation adsorption on silica surface: How the adsorbed layer responds to changes in bulk solution
- 2005
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 21:13, s. 5872-5881
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Tidskriftsartikel (refereegranskat)abstract
- Adsorption of cationic high molecular weight polyacrylamides (CPAM) (M-w is about 800 kDa) with different fractions of cationic units tau = 0.09 and tau = 0.018 onto silica surface was studied over a wide range of pH (4-9) and KCl concentration (c(s) = 10(-3)-10(-1) M) by in-situ null ellipsometry. We discuss how the adsorbed layer depends on the bulk conditions as well as kinetically responds to changes in solution conditions. The adsorbed amount F of CPAM increases with pH for all studied electrolyte concentrations until a plateau F is reached at pH > 6. At low pH we observed an increase in adsorbed amount with electrolyte concentration. At high pH there is no remarkable influence of added salt on the values of the adsorbed amount. The thickness of adsorbed polymer layers, obtained by ellipsometry, increases with electrolyte concentration and decreases with pH. At low c(s) and high pH the polyelectrolyte adsorbs in a flat conformation. An overcompensation of the surface charge (charge reversal) by the adsorbed polyelectrolyte is observed at high c, and low pH. To reveal the reversibility of the polyelectrolyte adsorption with respect to the adsorbed amount and layer thickness, parameters such as polyelectrolyte concentration (cp), c(s) and pH were changed during the experiment. Generally, similar adsorbed layer properties were obtained independent of whether adsorption was obtained directly to initially bare surface or by changing pH, c(s) or the concentration of polyelectrolyte solution in the presence of a preadsorbed layer, provided that the coverage of the preadsorbed layer was low. Once a steady state of the measured parameters (Gamma, d) was reached, experimental conditions were restored to the original values and corresponding changes in Gamma and adsorbed layer thickness were recorded. For initially low surface coverage it was impossible to restore the layer properties, and in this case we always ended up with higher coverage than the initial values. For initial high surface coverage it was usually possible to restore the initial layer properties. Thus, we concluded that polyelectrolyte appears only partially reversible to changes in the solution conditions due the slow rearrangement process within the adsorbed layer.
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| 11. |
- Talaikyte, Z, et al.
(författare)
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Interactions of cyclic AMP and its dibutyryl analogue with a lipid layer in the aqueous mixtures of monoolein preparation and dioleoyl phosphatidylcholine as probed by X-ray diffraction and Raman spectroscopy
- 2004
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Ingår i: Journal of Biological Physics. - 0092-0606. ; 30:1, s. 83-96
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Tidskriftsartikel (refereegranskat)abstract
- Interactions of adenosine 3':5'-cyclic monophosphate (cAMP) and N-6,2'-O-dibutyryl-adenosine 3':5'-cyclic monophosphate (dbcAMP) with a lipid layer composed of monoolein-based preparation and dioleoyl phosphatidylcholine ( DOPC) were investigated by small-angle X-ray diffraction (SAXD) and Raman spectroscopy. The reversed hexagonal (H-II) MO/DOPC/H2O phase of 65:15:20 wt.% composition was selected as a reference system. SAXD revealed that entrapment (at the expense of water) of 3 wt.% cAMP into the reference system did not change the polymorphic form and structural parameters of the phase. The same content of dbcAMP induced the transition from the HII phase to the reversed bicontinuous cubic phase of space group Ia3d. This transition is explained by the increase of lipid head-group area due to the penetration of the acylated adenine group of dbcAMP into the polar/apolar region of lipid layer. The conclusion is supported by Raman spectroscopy, showing the disruption/weakening of hydrogen bonding in the MO/DOPC-based matrix at the N1- and N3-sites of the dbcAMP adenine ring. As distinct from dbcAMP, cAMP remains mostly in the water channels of the HII phase, although the phosphate residue of nucleotide interacts with the quaternary ammonium group of DOPC. Both nucleotides increase the population of gauche isomers in the DOPC choline group.
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| 12. |
- Tournillon, A-S, et al.
(författare)
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p53 binds the mdmx mRNA and controls its translation
- 2017
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Ingår i: Oncogene. - : NATURE PUBLISHING GROUP. - 0950-9232 .- 1476-5594. ; 36:5, s. 723-730
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Tidskriftsartikel (refereegranskat)abstract
- MDMX and MDM2 are two nonredundant essential regulators of p53 tumor suppressor activity. MDM2 controls p53 expression levels, whereas MDMX is predominantly a negative regulator of p53 trans-activity. The feedback loops between MDM2 and p53 are well studied and involve both negative and positive regulation on transcriptional, translational and post-translational levels but little is known on the regulatory pathways between p53 and MDMX. Here we show that overexpression of p53 suppresses mdmx mRNA translation in vitro and in cell-based assays. The core domain of p53 binds the 5' untranslated region (UTR) of the mdmx mRNA in a zinc-dependent manner that together with a trans-suppression domain located in p53 N-terminus controls MDMX synthesis. This interaction can be visualized in the nuclear and cytoplasmic compartment. Fusion of the mdmx 5' UTR to the ovalbumin open reading frame leads to suppression of ovalbumin synthesis. Interestingly, the transcription inactive p53 mutant R273H has a different RNA-binding profile compared with the wild-type p53 and differentiates the synthesis of MDMX isoforms. This study describes p53 as a trans-suppressor of the mdmx mRNA and adds a further level to the intricate feedback system that exist between p53 and its key regulatory factors and emphasizes the important role of mRNA translation control in regulating protein expression in the p53 pathway.
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