Qualitative and quantitative changes of CD44 expression are implicated in early stages of breast carcinogenesis. The restricted neo-expression of certain CD44 isoforms in breast neoplasias suggests that CD44 might be a potential target for future antibody-based tumour therapy.
Left ventricular assist devices (LVAD) may improve cardiac function. The pathogenesis of this phenomenon, called 'reverse remodelling', is not completely elucidated. To examine the hypothesis that LVAD support eliminates tissue stress by reducing local hypoxia, the distribution of heme oxygenase-1 (HO-1), a stress protein inducible by hypoxia, was examined in vivo and in vitro. The immunoreactivity for HO-1 was semi-quantitatively analysed in left ventricular tissue of 23 patients (14 dilated cardiomyopathy (DCM), six ischaemic heart disease (IHD), three myocarditis/congenital heart disease) with end-stage heart failure before and after LVAD support, while two unused donor hearts served as controls. Control hearts stained almost negative for HO-1, while failing hearts showed immunoreactivity mainly in cardiomyocytes, but also in endothelial cells, some smooth muscle cells and fibroblasts. Hearts with IHD showed significantly higher HO-1 immunoreactivity than hearts with DCM or myocarditis/congenital heart disease. After LVAD support, the HO-1 content decreased significantly in the DCM and IHD group and was significantly higher in the subendocardium than in the subepicardium. In vitro, under hypoxic conditions, neonatal rat cardiomyocytes showed an increase of HO-1 protein content up to sixfold above the normal level, which returned to normal values after normoxic cultivation. Mechanical support reduces the HO-1 content of the failing heart and HO-1 is inducible in vitro under hypoxia and is reversible under normoxia. This supports the concept that restoration of cardiac normoxia by mechanical unloading, particularly in the subendocardium, may be in part responsible for the phenomenon of 'reverse remodelling'.
Some of isoflurane's cellular actions, such as interference with intracellular Ca(2+) handling, inhibition of the respiratory chain, and the capability to produce oxygen radicals, could result in impaired cellular function during ischemia/reoxygenation (I/R). We investigated the effects of isoflurane applied during I/R on intracellular Ca(2+), oxygen radical formation, arrhythmic events, and contractile function in rat cardiomyocytes. Single ventricular myocytes were subjected to 30 min of simulated ischemia followed by 30 min of reoxygenation. After baseline measurements, isoflurane-treated cells were exposed to 1 minimum alveolar concentration of isoflurane in air, whereas control cells were exposed to air only. Cytosolic Ca(2+) overload was observed in the isoflurane group (P < 0.05). During ischemia, systolic cell shortening decreased in both groups. In the isoflurane group, arrhythmic events and hypercontracture occurred more often during I/R, and the recovery of contractility during reoxygenation was less marked (P < 0.05). Furthermore, increased oxygen radical generation was detected in isoflurane-treated myocytes during reoxygenation (P < 0.05). Isoflurane given during I/R in this study induced intracellular Ca(2+) accumulation and impaired cell function. These potentially harmful effects were associated with a diminished Ca(2+) clearance and an accelerated oxygen radical production.
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