A G Geppert | PubMed Health

PubMed1998

Chronic aortic dissection masquerading as systemic disease.

We report two cases of chronic aortic dissection whose prominent features were characterized by systemic symptoms (prolonged low grade fever, fatigue, weight loss) and biological acute phase response. In the first patient, a surgical repair of the descending thoracic aorta aneurysm was performed, allowing the disappearance of general manifestations, whereas spontaneous resolution occurred in the second case. Although aortic dissection is usually an acute and highly symptomatic event, the disorder can present--albeit rarely--as systemic illness and fever of unknown origin.

Acute-Phase Reaction↗

PubMed1992

Allosteric regulation of tPA-mediated plasminogen activation by a modifier mechanism: evidence for a binding site for plasminogen on the tPA A-chain.

We studied the mechanism responsible for nonlinear double reciprocal plots for tissue type plasminogen activator (tPA)-mediated plasminogen activation reported previously by several groups. We found nonlinear Eadie-Scatchard plots for Glu-plasminogen activation by recombinant single-chain tPA confirming a non-Michaelis-Menten behavior of tPA. In order to characterize this mechanism, enzyme kinetic studies with truncated substrates (Lys- and miniplasminogen) and modified or truncated enzymes (two-chain tPA and tPA B-chain) were performed. Thereby it could be excluded that product-mediated modifications of the enzyme or the substrate are responsible for the nonlinear plots. Linear plots, i.e., Michaelis-Menten kinetics, were only found when tPA B-chain was used as a plasminogen activator, indicating that the tPA A-chain should be responsible for the non-Michaelis-Menten behavior. Binding studies of plasminogen to immobilized tPA A-chain in fact demonstrated a saturable binding of Glu- and miniplasminogen to the A-chain of tPA with a KD approximately 0.1 microM and one binding site per molecule of tPA A-chain. These data suggested a modifier mechanism responsible for the nonlinear plots whereby the substrate plasminogen itself could function as a modifier. When such a mechanism was included into a model for tPA-mediated plasminogen activation, the experimentally obtained data could be fitted into such a model by nonlinear regression analysis with resulting p-values of less than 0.001.

Allosteric Regulation↗