| 1. |
- Ekstrom, Mattias, et al.
(författare)
-
Stimulated in vivo synthesis of plasminogen activator inhibitor 1 in human adipose tissue
- 2012
-
Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 108:3, s. 485-492
-
Tidskriftsartikel (refereegranskat)abstract
- Plasminogen activator inhibitor type-1 (PAI-1) is one of the most important inhibitors of endogenous fibrinolysis. Adipose tissue is a suggested source of the elevated plasma levels o(-) PAI-1 in obesity. The relation between PAI-1 and inflammation is of particular interest, but current knowledge regarding regulation of PAI-1 in adipose tissue is mainly based on animal studies or ex vivo experiments on human cultured adipocytes. So far, no study has described stimulated gene expression and protein synthesis of PAI-1 in vivo in human adipose tissue. We used open heart surgery as a model of acute systemic inflammation. Twenty-two male patients underwent blood sampling and omental and subcutaneous adipose tissue biopsies for gene expression studies before and after surgery. Expression and localisation of PAI-1 antigen was evaluated by immunohistochemistry. After surgery gene expression of PAI-1 increased 27-fold in omental adipose tissue and three-fold in subcutaneous adipose tissue, but no differences were found in tissue-type plasminogen activator (t-PA) mRNA. PAI-1 antigen was localised within endothelial cells and in the adipose tissue interstitium close to vessels. The upregulated gene expression and protein synthesis in adipose tissue was followed by increased concentrations of PAI-1 antigen in plasma. In conclusion, we present for the first time that an acute systemic inflammation in humans increased gene expression and protein synthesis of PAI-1 in adipose tissue and that this increase was most prominent in omental adipose tissue. PAI-1 synthesis in adipose tissue due to acute systemic inflammation may be a link between inflammation and impaired endogenous fibrinolysis.
|
|
| 2. |
- Hartman, Robert J.
(författare)
-
Concomitant ignorance excuses from moral responsibility
- 2021
-
Ingår i: Thought. - : Philosophy Documentation Center. - 0340-6245 .- 2161-2234. ; 10:1, s. 58-65
-
Tidskriftsartikel (refereegranskat)abstract
- Some philosophers contend that concomitant ignorance preserves moral responsibility for wrongdoing. An agent is concomitantly ignorant with respect to wrongdoing if and only if her ignorance is non-culpable, but she would freely have performed the same action if she were not ignorant. I, however, argue that concomitant ignorance excuses. I show that leading accounts of moral responsibility imply that concomitant ignorance excuses, and I debunk the view that concomitant ignorance preserves moral responsibility.
|
|
| 3. |
- Johannesson, Eric, 1982-, et al.
(författare)
-
The A Priori-Operator and the Nesting Problem
- 2016
-
Ingår i: Thought. - : Philosophy Documentation Center. - 0340-6245 .- 2161-2234. ; 5:3, s. 169-176
-
Tidskriftsartikel (refereegranskat)abstract
- Many expressions intuitively have different epistemic and modal profiles. For example, co-referring proper names are substitutable salva veritate in modal contexts but not in belief-contexts. Two-dimensional semantics, according to which terms have both a so-called primary and a secondary intension, is a framework that promises to accommodate and explain these diverging intuitions. The framework can be applied to indexicals, proper names or predicates. Graeme Forbes (2011) argues that the two-dimensional semantics of David Chalmers (2011) fails to account for so-called nested contexts. These are linguistic contexts where a sentence is embedded under both epistemic and modal operators. Chalmers and Rabern (2014) suggest a two-dimensional solution to the problem. Their semantics solves the nesting-problem, but at the cost of invalidating certain plausible principles. We suggest a solution that is both simpler and avoids this cost.
|
|
