Transforming growth factor alpha (TGF-alpha), epidermal growth factor (EGF), and related factors mediate their biological effects by binding to the extracellular domain of the EGF receptor, which leads to activation of the receptor's cytoplasmic tyrosine kinase activity. Much remains to be determined, however, about the detailed molecular mechanism involved in this ligand-induced receptor activation. The determination of the binding mechanism and the related thermodynamic and kinetic parameters are of prime importance. To do so, we have used a surface plasmon resonance-based biosensor (the BIAcore) that allows the real-time recording of the interaction between TGF-alpha and the extracellular domain of the EGF receptor. By immobilizing different biotinylated derivatives of TGF-alpha on the sensor chip surface, we demonstrated that the N-terminus of TGF-alpha is not directly involved in receptor binding. By optimizing experimental conditions and interpreting the biosensor results by several data analysis methods, we were able to show that the data do not fit a simple binding model. Through global analysis of the data using a numerical integration method, we tested several binding mechanisms for the TGF-alpha/EGF receptor interaction and found that a conformational change model best fits the biosensor data. Our results, combined with other analyses, strongly support a receptor activation mechanism in which ligand binding results in a conformation-driven exposure of a dimerization site on the receptor.

Pacemaker lead extraction has been shown to be an effective and safe treatment in the case of infected per-manent pacemaker leads. However, it can lead to potentially serious complications, usually occurring during the ex-traction procedure. This report describes a case of a 74-year-old male with a persistent superior vena cava thrombo-sis related to an infected permanent pacemaker lead transvenous extraction. Clinical and surgical management are discussed.

The purpose of this study was to determine the cumulative effects of brief intervals of hypoxia and hypercapnia on the pulsatile characteristics of the pulmonary arterial circulation of 48-h-old compared with 2-wk-old open-chest Yorkshire pigs while using two different anesthetic regimens: 1) azaperone and ketamine (4 and 12 mg/kg im, respectively) and 2) thiopental sodium (25 mg/kg i.v.). Animals 48 h old were randomly allocated to undergo mild hypoxia (inspired O2 fraction = 0.15), severe hypoxia (inspired O2 fraction = 0.05), or hypercapnia (inspired CO2 fraction = 0.20), whereas animals 2 wk old underwent severe hypoxia or hypercapnia. With use of Fourier analysis, characteristic impedance (Zo), mean input impedance (Zm), impedance moduli, and phase angles were determined. In 48-h-old pigs anesthetized with azaperone-ketamine, neither mild nor severe hypoxia altered Zo, Zm, or pulmonary vascular resistance (PVR), whereas hypercapnia increased Zo by 22% (P < 0.001), which persisted despite a return to normocapnia. In 48-h-old animals anesthetized with thiopental, baseline control Zo and Zm were lower than those in same-age pigs anesthetized with azaperone-ketamine. In thiopental-anesthetized 48-h-old pigs, both severe hypoxia and hypercapnia increased Zm and PVR but Zo was unaltered. In 2-wk-old pigs anesthetized with thiopental, severe hypoxia but not hypercapnia elevated Zm and PVR, whereas Zo was not changed with either stress. Results indicate age- and anesthetic-dependent responses of Zo, Zm, and PVR to severe hypoxia and hypercapnia. The persistent elevation in Zo caused by hypercapnia indicates a prolonged decrease in arterial compliance or a reduction in effective proximal pulmonary arterial radius.