Biomedical subjects

Stefan Seidl

Publications and source records attributed to Stefan Seidl.

7 recordsLinked to original sources

PubMed2006

The CX3C chemokine fractalkine induces vascular dysfunction by generation of superoxide anions.

OBJECTIVE: The chemokine fractalkine activates platelets and induces leukocyte adhesion to the endothelium. Expression of fractalkine and its receptor, CX3CR1, is elevated in coronary artery disease. We assessed the effects of fractalkine on vascular function in isolated rat aorta. METHODS AND RESULTS: CX3CR1 expression was demonstrated in rat aortic endothelial and smooth muscle cells by immunohistochemistry, Western blot, and polymerase chain reaction (PCR). Fractalkine (up to 1 microg/mL) did not directly induce contractile or relaxant responses when applied to rat aortic rings in organ baths. Short-term incubation with fractalkine (1 microg/mL) for 5 minutes did not affect vascular reactivity. Pretreatment of isolated rat aortic rings with fractalkine for 2 hours impaired acetylcholine-induced nitric oxide (NO)-mediated relaxation after preconstriction with phenylephrine in a concentration-dependent manner. The concentration response to the NO donor DEA-NONOate was significantly shifted to the right. The radical scavenger tiron normalized the attenuated acetylcholine-induced relaxation after fractalkine incubation. Aortic superoxide formation was enhanced by fractalkine, which was inhibited by diphenyleneiodonium but not by inhibitors of xanthine oxidase or NO synthase. CONCLUSIONS: In addition to its role as a chemokine and adhesion molecule, fractalkine induces vascular dysfunction by stimulating vascular reactive oxygen species resulting in reduced NO bioavailability.

Acetylcholine↗

PubMed2006

Noninvasive characterization of myocardial molecular interventions by integrated positron emission tomography and computed tomography.

OBJECTIVES: We sought to investigate the usefulness of integrated positron emission tomography (PET) and computed tomography (CT) for in vivo characterization of an angiogenesis-directed molecular intervention. BACKGROUND: Controversies about the effectiveness of molecular therapies for cardiovascular disease have prompted the need for more powerful noninvasive imaging techniques. METHODS: In a model of regional adenoviral transfer of the VEGF(121) gene to myocardium of healthy pigs, PET-CT using multiple molecular-directed radiotracers was employed. RESULTS: Two days after gene transfer, successful transgene expression was noninvasively confirmed by a reporter probe targeting co-expressed HSV1-sr39tk reporter gene. The CT-derived ventricular function and morphology remained unaltered (left ventricular ejection fraction 57 +/- 5% in adenovirus-injected animals vs. 53 +/- 5% in controls; p = 0.36). Increased regional perfusion was identified in areas overexpressing VEGF (myocardial blood flow during adenosine-induced vasodilation 1.47 +/- 0.49 vs. 1.14 +/- 0.27 ml/g/min in remote areas; p = 0.01), corroborating in vivo effects on microvascular tone and permeability. Finally, regional angiogenesis-associated alpha(v)beta3 integrin expression was not enhanced, suggesting little contribution to the perfusion increase. Fusion of CT morphology and tracer-derived molecular signals allowed for accurate regional localization of biologic signals. Findings were validated by control vectors, sham-operated animals, and ex vivo tissue analysis. CONCLUSIONS: Integrated PET-CT has the potential to dissect cardiovascular biologic mechanisms from gene expression to physiologic function and morphology. The VEGF overexpression in healthy myocardium increases myocardial perfusion without significant up-regulation of alpha(v)beta3 integrin adhesion molecules early after the intervention.

Animals↗

PubMed2006

Rectal carcinoma: high-spatial-resolution MR imaging and T2 quantification in rectal cancer specimens.

PURPOSE: To prospectively compare high-spatial-resolution T1-weighted, T2-weighted, and intermediate-weighted spectral fat-saturated magnetic resonance (MR) imaging for the differentiation of tumor from fibrosis and for delineation of rectal wall layers in rectal cancer specimens. MATERIALS AND METHODS: The local ethics committee approved the protocol, and written informed consent was obtained from each patient. Thin-section high-spatial-resolution MR imaging was performed in specimens obtained from 23 patients (16 men, seven women; median age, 64 years; age range, 39-84 years) immediately after resection. Seven patients underwent neoadjuvant treatment. T1-weighted spin-echo, T2-weighted fast spin-echo, and intermediate-weighted spectral fat-saturated MR images were obtained in the transverse plane. Differences in signal intensity between tumor and fibrosis and between tumor and rectal wall layers were evaluated by using visual scoring and measurements of T2 relaxation time. Statistical differences were evaluated by using the Wilcoxon signed rank test and a mixed-model regression analysis. All images were compared with whole-mount histopathologic slices (n = 86). RESULTS: T2-weighted MR images provided the best differentiation between tumor and fibrosis (P < .001). Mean visual signal intensity scores were -1.8 for T2-weighted MR images, -1.4 for intermediate-weighted spectral fat-saturated MR images, and -0.2 for T1-weighted MR images. T2 relaxation times were 97 msec +/- 4.6 for tumor and 70 msec +/- 3.8 for fibrosis (P < .001). Substantial overlap was noted between the tumor and the circular layer of the muscularis propria (97 msec +/- 2.1), and less overlap was noted between the tumor and the longitudinal layer of the muscularis propria (88 msec +/- 1.6). CONCLUSION: T2-weighted MR imaging provides superior delineation of rectal wall layers and better differentiation of tumor from fibrosis in rectal cancer specimens compared with T1-weighted MR imaging and intermediate-weighted spectral fat-saturated MR imaging by using thin-section high-spatial-resolution sequences.

Adult↗

PubMed2006

Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo.

The accumulation of smooth muscle and endothelial cells is essential for remodeling and repair of injured blood vessel walls. Bone marrow-derived progenitor cells have been implicated in vascular repair and remodeling; however, the mechanisms underlying their recruitment to the site of injury remain elusive. Here, using real-time in vivo fluorescence microscopy, we show that platelets provide the critical signal that recruits CD34+ bone marrow cells and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells to sites of vascular injury. Correspondingly, specific inhibition of platelet adhesion virtually abrogated the accumulation of both CD34+ and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells at sites of endothelial disruption. Binding of bone marrow cells to platelets involves both P-selectin and GPIIb integrin on platelets. Unexpectedly, we found that activated platelets secrete the chemokine SDF-1alpha, thereby supporting further primary adhesion and migration of progenitor cells. These findings establish the platelet as a major player in the initiation of vascular remodeling, a process of fundamental importance for vascular repair and pathological remodeling after vascular injury.

Animals↗

PubMed2005

Targeting 2A protease by RNA interference attenuates coxsackieviral cytopathogenicity and promotes survival in highly susceptible mice.

BACKGROUND: Enteroviridae such as coxsackievirus B3 (CVB3) are important infectious agents involved in viral heart disease, hepatitis, and pancreatitis, but no specific antiviral therapy is available. METHODS AND RESULTS: The aim of the present study was to evaluate the impact of RNA interference on viral replication, cytopathogenicity, and survival. Small interfering RNA (siRNA) molecules were designed against the viral 2A region (siRNA-2A), which is considered to be highly conserved and essential for both virus maturation and host cytopathogenicity. siRNA-2A exhibited a significant protective effect on cell viability mediated by marked inhibition of CVB3 gene expression and viral replication. In highly susceptible type I interferon receptor-knockout mice, siRNA-2A led to significant reduction of viral tissue titers, attenuated tissue damage, and prolonged survival. Repeated siRNA-2A transfection was associated with a further improvement of survival. Various control siRNA molecules had no protective effect in vitro or in vivo. CONCLUSIONS: RNA interference directed against the 2A protease encoding genomic region effectively confers intracellular immunity toward CVB3-mediated cell injury and improves survival, suggesting a potential role for RNA interference for future treatment options targeting enteroviral diseases.

Animals↗

PubMed2004

Voltage-controlled optics of a quantum dot.

We show how the optical properties of a single semiconductor quantum dot can be controlled with a small dc voltage applied to a gate electrode. We find that the transmission spectrum of the neutral exciton exhibits two narrow lines with approximately 2 mueV linewidth. The splitting into two linearly polarized components arises through an exchange interaction within the exciton. The exchange interaction can be turned off by choosing a gate voltage where the dot is occupied with an additional electron. Saturation spectroscopy demonstrates that the neutral exciton behaves as a two-level system. Our experiments show that the remaining problem for manipulating excitonic quantum states in this system is spectral fluctuation on a mueV energy scale.

Journal Article↗

PubMed2002

Combined transcriptome and genome analysis of single micrometastatic cells.

In human cancer, early systemic spread of tumor cells is recognized as a leading cause of death. Adjuvant therapies are administered to patients after complete resectioning of their primary tumors to eradicate the few residual and latent metastatic cells. These therapeutic regimens, however, are currently designed without direct information about the presence or nature of the latent cells. To address this problem, we developed a PCR-based technique to analyze the transcriptome of individual tumor cells isolated from the bone marrow of cancer patients. From the same cells, genomic aberrations were identified by comparative genomic hybridization. The utility of this approach for understanding the biology of occult disseminated cells and for the identification of new therapeutic targets is demonstrated here by the detection of frequent extracellular matrix metalloproteinase inducer (EMMPRIN; CD147) expression which was verified by immunostaining.

Cell Cycle↗