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- Björk, Ingemar, et al.
(författare)
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Probing the functional role of the N-terminal region of cystatins by equilibrium and kinetic studies of the binding of Gly-11 variants of recombinant human cystatin C to target proteinases
- 1995
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Ingår i: Biochemical Journal. - 0264-6021. ; 306:2, s. 513-518
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between cystatin C variants, in which the evolutionarily conserved Gly-11 residue was substituted by Ala, Glu or Trp, and the cysteine proteinases, papain, ficin, actinidin and cathepsin B, was characterized. The substitutions reduced the affinity of binding in a manner consistent with the Gly residue of the wild-type inhibitor, allowing the N-terminal region to adopt a conformation that was optimal for interaction with target proteinases. Replacement of Gly-11 by Ala resulted in only a 5- to 100-fold reduction in binding affinity. Comparison with the affinities of wild-type cystatin C lacking the N-terminal region indicated that even this small structural change affects the conformation of this region sufficiently to largely abolish its interaction with the weakly binding proteinases, actinidin and cathepsin B. However, the substitution allows interactions of appreciable strength between the N-terminal region and the tightly binding enzymes, papain or ficin. Replacement of Gly-11 with the larger Glu and Trp residues substantially decreased the affinity of binding to all enzymes, from 10(3)- to 10(5)-fold. These substitutions further affect the conformation of the N-terminal region, so that interactions of this region with papain and ficin are also essentially eliminated. The decreased affinities of the three cystatin C variants for papain, ficin and actinidin were due exclusively to increased dissociation rate constants. In contrast, the decreased affinity between cathepsin B and the Ala-11 variant, the only one for which rate constants could be determined with this enzyme, was due almost entirely to a decreased association rate constant. This behaviour is analogous to that observed for forms of cystatin C lacking the N-terminal region and supports the conclusion that the mode of interaction of this region with target proteinases varies with the enzyme as a result of structural differences in the active-site region of the latter.
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- Björk, Tabita, et al.
(författare)
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Eating disorders and anabolic androgenic steroids in males : similarities and differences in self-image and psychiatric symptoms
- 2013
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Ingår i: Substance Abuse Treatment, Prevention, and Policy. - 1747-597X. ; 8:30, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Body dissatisfaction is common among both females and males. Dissatisfaction with the body is a risk factor both for onset of eating disorders and for abuse of anabolic androgenic steroids (AAS). Few studies have however investigated if there are other similarities in respect to self-image or psychiatric symptoms between clinical samples of eating disordered males and males in treatment for negative effects of AAS use.Aim: The aim of this study was to compare two clinical samples, one of males with ED and one of males who used AAS, regarding self-image and psychiatric symptoms.Methods: This study compared males with eating disorders (n = 13) and males who recently stopped AAS use (n = 29) on self-image and psychiatric symptoms, using The Structural Analysis of Social Behavior self-questionnaire and a shortened version of The Symptom Check List.Results: The eating disorder group reported significantly lower scores for Self-emancipation and Active self-love and higher scores for Self-blame and Self-hate. Both groups reported serious psychiatric symptoms. The common denominator between groups was serious psychiatric symptomatology rather than negative self-image.Conclusions: The negative self-image profile, especially self-hate, found among males with Eating Disorders may indicate that the studied groups differ in aetiology of the underlying problems. The serious psychiatric symptoms in both groups call staff to pay attention to any thoughts of suicide due to severe depressive symptoms where by specialized psychiatric treatment may be needed.
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| 9. |
- Manea Hedström, Minola, et al.
(författare)
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ADAMTS13 phenotype in plasma from normal individuals and patients with thrombotic thrombocytopenic purpura.
- 2007
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Ingår i: European Journal of Pediatrics. - : Springer Science and Business Media LLC. - 1432-1076 .- 0340-6199. ; 166:3, s. 249-257
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Tidskriftsartikel (refereegranskat)abstract
- The activity of ADAMTS 13, the von Willebrand factor cleaving protease, is deficient in patients with thrombotic thrombocytopenic purpura (TTP). In the present study, the phenotype of ADAMTS13 in TTP and in normal plasma was demonstrated by immunoblotting. Normal plasma (n=20) revealed a single band at 190 kD under reducing conditions using a polyclonal antibody, and a single band at 150 kD under non-reducing conditions using a monoclonal antibody. ADAMTS 13 was not detected in the plasma from patients with congenital TTP (n=5) by either antibody, whereas patients with acquired TTP (n=2) presented the normal phenotype. Following immunoadsorption of immunoglobulins, the ADAMTS 13 band was removed from the plasma of the patients with acquired TTP, but not from that of normal individuals. This indicates that ADAMTS13 is complexed with immunoglobulin in these patients. The lack of ADAMTS13 expression in the plasma from patients with hereditary TTP may indicate defective synthesis, impaired cellular secretion, or enhanced degradation in the circulation. This study differentiated between normal and TTP plasma, as well as between congenital and acquired TTP. This method may, therefore, be used as a complement in the diagnosis of TTP.
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| 10. |
- Mehmeti, Meliha, et al.
(författare)
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Wnt5a is a TLR2/4-ligand that induces tolerance in human myeloid cells
- 2019
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Innate immune responses are rapid, dynamic and highly regulated to avoid overt reactions. This regulation is executed by innate immune tolerance mechanisms that remain obscure. Wnt5a is a signalling protein mainly involved in developmental processes and cancer. The effect of Wnt5a on inflammatory myeloid cells is controversial. Here, we combine primary cell cultures, in vitro binding studies, mass spectrometry and Drosophila protein modelling to show that Wnt5a is a direct ligand of toll-like receptor (TLR) 2 and 4. The binding promotes a MyD88-non-canonical nuclear factor of kappa B (NFκB) and AP-1 signalling cascade, with contradictory profiles in mouse (pro-inflammatory) and human (anti-inflammatory) myeloid immune cells. These data reveal that the true nature of Wnt5a in inflammatory cells, is to regulate TLR signals, and in human myeloid cells it acts as an endogenous, tolerance-associated molecular pattern (TAMP), inducing IL-10 and innate immune tolerance.
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