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Biomedical subjects

E Neubauer

Publications and source records attributed to E Neubauer.

9 recordsLinked to original sources

Receptor-independent role of the urokinase-type plasminogen activator during arteriogenesis.

To define the role of the plasminogen activators (PAs) urokinase PA (uPA) and tissue PA (tPA) as well as the uPA receptor (uPAR) in arteriogenesis, we investigated their impact in a rabbit and mouse model of adaptive collateral artery growth. Collateral artery growth was induced by occlusion of the femoral artery in rabbit and wild-type (WT) mice and in mice with targeted inactivation of uPA (uPA-/-), tPA (tPA-/-), or uPAR (uPAR-/-). Northern blot results revealed a significant up-regulation of uPA but not uPAR or tPA in the early phase of arteriogenesis in rabbit and WT mice. This up-regulation on RNA level was followed by an increased protein level and enzymatic activity. Impaired perfusion recovery upon femoral artery ligation was observed by laser Doppler analysis in vivo in uPA-deficient mice but not in uPAR or tPA deficiency compared with WT mice. Immunohistochemical studies revealed an association of leukocyte infiltration with arteriogenesis in WT mice that was strongly reduced in uPA-/- but not in uPAR- or tPA-deficient mice. We conclude that arteriogenesis is promoted by an uPA-mediated infiltration of leukocytes that is not dependent on uPAR.

Animals↗

Effect of intermittent high altitude hypoxia on gene expression in rat heart and lung.

Hypoxia has been identified as an important stimulus for gene expression during embryogenesis and in various pathological situations. Its influence under physiological conditions, however, has only been studied occasionally. We therefore investigated the effect of intermittent high altitude hypoxia on the mRNA expression of different cytokines and protooncogenes, but also of other genes described to be regulated by hypoxia, in the left ventricle (LV), the right ventricle (RV), atria and the lung of adult rats after simulation of hypoxia in a barochamber (5000 m, 4 hours to 10 days). Heme oxygenase-1 as well as transforming growth factor-beta1 showed an increased expression in all regions of the heart and the lung at different periods of hypoxia. For lactate dehydrogenase-A, we found a significant up-regulation in the RV and the lung, for lactate dehydrogenase-B up-regulation in the RV, but down-regulation in the LV and the atria. Vascular endothelial growth factor was up-regulated in the RV, the LV and the lung, but down-regulated in the atria. Its receptor Flk-1 mRNA was significantly increased in the atria and RV only. Expression of c-fos was found in the LV and RV only after 4 hours of hypoxia. The level of c-jun was significantly increased in the LV but decreased in the atria. Our data clearly demonstrate that intermittent hypoxia is a modulator of gene expression under physiological conditions. It differently regulates the expression of distinct genes not only in individual organs but even within one organ, i.e. in the heart.

Adaptation, Physiological↗

Head-to-head comparison of N-terminal pro-brain natriuretic peptide, brain natriuretic peptide and N-terminal pro-atrial natriuretic peptide in diagnosing left ventricular dysfunction.

Brain natriuretic peptide (BNP), NT-proBNP and NT-pro-atrial natriuretic peptide (NT-proANP) were measured in blood samples from 57 patients using immunoassays and immunoradiometric assays to evaluate the usefulness as diagnostic markers for the detection of heart failure. For the detection of impaired left ventricular ejection fraction (LVEF), receiver operating characteristic curves showed that BNP had the best diagnostic performance with an area under curve (AUC) of 0.75+/-0.06. However, NT-proBNP (AUC: 0.67+/-0.07) and NT-proANP (AUC: 0.69+/-0.08) showed no significant difference to BNP. In a further analysis for the detection of resting LVEF <40%, BNP again was the best marker with an AUC of 0.83+/-0.06. NT-proBNP showed only a slightly smaller AUC (0.79+/-0.07). The AUC for NT-proANP was significantly smaller (0.65+/-0.08) compared to BNP. Additionally, BNP and NT-proBNP correlated negatively with the resting LVEF (BNP: -0.472, p<0.001; NT-proBNP: -0.306, p=0.026), whereas NT-proANP showed no significant correlation. In summary, BNP was the best marker to detect patients with impaired LVEF compared to NT-proBNP and NT-proANP. However, NT-proBNP showed no significant differences to BNP and it is therefore a new promising alternative marker for the detection of left ventricular dysfunction.

Aged↗

Bone mineral content after renal transplantation. Placebo-controlled prospective study with 1,25-dihydroxy vitamin D3.

Forearm bone mineral content (BMC), as evaluated by photonabsorption densitometry, was measured in 28 cadaver kidney donor recipients who entered the study 8 weeks postoperatively and were followed up for 18 months. BMC decreased significantly (p less than 0.05) but marginally in placebo-treated patients (n = 14) (initial BMC 1.09 +/- 0.25 g/cm; final BMC 1.05 +/- 0.24). Fourteen patients were prophylactically given 1,25(OH)2 vitamin D3 in a dose which avoided hypercalcemia and hypercalciuria (approximately 0.25 microgram/day); under 1,25(OH)2 vitamin D3 prophylaxis a significant decrease of forearm BMC was observed no longer (initial BMC 0.94 +/- 0.21 g/cm; final BMC 0.95 +/- 0.21), but the difference between placebo and 1,25(OH)2 vitamin D3 narrowly missed statistical significance (p = 0.066). It is concluded that the decrease of forearm BMC is negligible in transplant recipients with low steroid regimens. The data suggest a trend for prophylaxis with 1,25(OH)2 vitamin D3 to slightly ameliorate forearm (cortical) BMC loss.

Adult↗

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Botany↗