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Michael Bitzer

Publications and source records attributed to Michael Bitzer.

14 recordsLinked to original sources
PubMed2004

Synchronous gastrointestinal and musculoskeletal manifestations of different subtypes of inflammatory myofibroblastic tumor: CT, MRI and pathological features.

We describe a case of an unusual multicentric appearance of an inflammatory myofibroblastic tumor, consisting of multiple gastrointestinal masses with different growth patterns and simultaneous, distant, musculoskeletal manifestations. CT and MR imaging features demonstrated a different degree of lesion enhancement, which proved histologically to be related to an alternation of predominantly spindle cell areas with a myxoid-vascular IMT subtype. A clear separation of the imaging characteristics of this tumor's subtypes by correlation with the pathology was not possible because of the mixed histologic character of the tumor in all its locations. However, MRI signal in the T2-weighted sequence was lower in the spindle cell variant localized predominantly in the musculoskeletal system, while the gastrointestinal predominantly myxoid-vascular counterparts showed slightly higher signal in the T2-weighted sequence.

Aged↗
PubMed2004

Recurrent spinal fistula as result of a rare combination of a perimedullary and peridural spinal fistula: case report.

OBJECTIVES: We report on a patient with the combination of a peridural and a perimedullary spinal fistula, which manifested consecutively. The clinical course and diagnostic steps reveal important observations helpful in the management of this pathology. CASE PRESENTATION: A 61-year-old male patient presented with a six-month history of progressive weakness of the lower limbs. Magnetic resonance imaging revealed edema and dilated spinal veins of the lower thoracic spinal cord. Spinal angiography confirmed the diagnosis of spinal dural fistula at level T9 on the left. The patient underwent surgery and the fistula was surgically excised. Two months after initial improvement, the clinical symptoms of lower limb weakness recurred. On re-angiography a spinal perimedullary fistula was found at level T7 that was not apparent on the previous angiogram and on the postoperative control angiogram. The patient underwent surgery again, and the second fistula was also excised. The clinical symptoms subsequently improved. CONCLUSION: The interesting point in this case was the rare combination of a peridural and a perimedullary spinal fistula. They presented consecutively and could not be identified simultaneously on the first angiogram. Only after closure of the first fistula did the second become apparent. We believe that this may be a result of a postoperative pressure change in the venous system of the cord. After closure of the first fistula, the arterio-venous (AV) shunt of the second fistula developed gradually. The possibility of a second fistula should be considered in the presence of persistent edema of the cord on magnetic resonance imaging (MRI) and subsequent clinical deterioration.

Angiography↗
PubMed2004

Efficient propagation of single gene deleted recombinant Sendai virus vectors.

Recombinant Sendai virus vectors (SeVV) have become an attractive tool for basic virological as well as for gene transfer studies. However, to (i) reduce the cellular injury induced by basic recombinant SeV vectors (encoding all six SeV genes as being present in SeV wild-type (wt) genomes) and to (ii) improve SeV vector safety, deletions of viral genes are necessary for the construction of superior SeVV generations. As a strong expression system recombinant replication-incompetent adenoviruses, coding for SeV proteins hemagglutinin-neuraminidase (HN), fusion (F), or matrix (M), were generated and successfully employed for the propagation of single gene deleted (DeltaHN, DeltaF, DeltaM) recombinant SeVV. Further investigations of the propagation procedures required for single gene deleted recombinant SeVV demonstrated (i) modifications of the cell culture medium composition as well as (ii) incubation with vitamin E as crucial steps for the enhancement of SeVV-DeltaHN, -DeltaF, or -DeltaM viral particle yield. Such optimized propagation procedures even led to a successful propagation of HN-deleted viral particles (SeVV-DeltaHN), which has not been reported before.

Adenoviridae↗
PubMed2004

Recombinant Sendai virus for efficient gene transfer to human airway epithelium.

Recombinant Sendai virus (rSeV) infects respiratory epithelial cells in animal models and cultures of undifferentiated human nasal cells. It was the aim of this study to investigate the capability of rSeV to express a transgene in human airway epithelium. Differentiated human airway epithelial cells were generated using air-liquid interface culture techniques. Application of rSeV coding for green fluorescence protein (GFP) onto the apical surface (using a multiplicity of infection of 3) resulted in expression of the transgene in more than 90% of the cells followed by decreasing numbers of positive cells during the observation time of 3 weeks. The infection of human respiratory epithelial cells is mediated by sialic acid residues at the apical surface. Despite the secretion of interleukin (IL)-8 and the replication of rSeV in the epithelial cells, the authors could not detect any cytopathic effect after the infection. In conclusion, rSeV infects differentiated human airway epithelial cells with high efficiency. Transgene expression is transient and accompanied by the secretion of an inflammatory cytokine.

Bronchi↗
PubMed2004

The benefit of functional-anatomical imaging with [18F]fluorodeoxyglucose utilizing a dual-head coincidence gamma camera with an integrated X-ray transmission system in non-small cell lung cancer.

AIM: To evaluate functional-anatomical imaging with 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) utilizing a dual-head coincidence gamma camera with an integrated X-ray transmission system for attenuation correction, anatomical mapping, and image fusion compared to conventional diagnostics by computed tomography (CT) in non-small cell lung cancer (NSCLC). METHODS: Thirty-five patients with NSCLC underwent FDG imaging of the thoracic area using a dual-head coincidence gamma camera (DHC) with an integrated X-ray transmission system. State-of-the-art CT scans had been performed before. Whole-body dedicated FDG positron emission tomography (PET) was performed immediately prior to DHC. Staging by CT and DHC, and DHC with integrated image fusion (FDHC) were re-evaluated with regard to detectable lesions, correct anatomical diagnoses, and clinical impact. Results of DHC and PET were compared for analysis of limitations of DHC. RESULTS: One hundred and thirteen tumour lesions were identified by CT. DHC detected 128 lesions overall: 102 true positive CT lesions were confirmed, 25 additional lesions were detected which affected staging in eight patients, and one false positive lung lesion did not show up in DHC. Nine CT lesions were missed by DHC (lymph node and lung). PET detected 150 areas of focally enhanced uptake, delivering two false positive results (nuchal muscles, pneumonia). Final evaluation confirmed 148 malignant lesions. Compared to CT, the results of DHC changed staging or treatment in 8/35 patients (23%). Lesion detection by DHC was limited by tumour size and intensity of FDG uptake. Image fusion provided relevant clinical information in 9/35 patients (26%). CONCLUSION: Functional imaging in NSCLC with this dual-head gamma camera is superior to morphological imaging by CT, although inferior to dedicated PET imaging. Combined functional-anatomical imaging has the potential to improve staging and localization procedures before surgery or radiotherapy.

Adult↗
PubMed2004

Preoperative marking of musculoskeletal tumors guided by magnetic resonance imaging.

BACKGROUND: The purpose of this study was to evaluate a new stereotactic method for preoperative coil-marking of musculoskeletal tumors with use of interventional magnetic resonance imaging. METHODS: Nine patients with a soft-tissue or bone-marrow tumor were referred to our department for preoperative marking of the extent of the lesion. In one patient, two lesions were marked. Guidance for the punctures and the delivery of the coils was provided by an open low-field magnetic resonance imaging system with horizontal access. After imaging of the extent of the lesion, magnetic resonance imaging-compatible titanium coils were placed with use of nearly real-time or step-by-step magnetic resonance imaging control. The coils were placed up to seventy-two hours before the surgery. The inclusion of the tumor borders within the area of the excision was examined with cross-sectional histological analysis of surgical specimens. RESULTS: The tumor-marking intervention was successfully performed with the guidance of magnetic resonance imaging only in all patients. Preoperatively, nineteen coils were used to mark the ten lesions in the nine patients. All of the coils were easily located with intraoperative fluoroscopy. No coil migrated between the time of the percutaneous marking and the surgery. Histological examination of the resection borders revealed no residual tumor cells. No complications were observed, and, after a mean of twenty-three months of follow-up, no tumor had recurred. CONCLUSIONS: Preoperative coil-marking guided by magnetic resonance imaging for exact delineation of a musculoskeletal tumor is technically feasible and can readily demonstrate the full extent of the tumor. Use of magnetic resonance fluoroscopy reduces the time needed for the intervention. We recommend the coil-marking technique.

Adult↗
PubMed2003

Adenoviral gene transfer of tumor necrosis factor-related apoptosis-inducing ligand overcomes an impaired response of hepatoma cells but causes severe apoptosis in primary human hepatocytes.

Ligands of the tumor necrosis factor family play key roles in liver pathogenesis. The ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is unique, because it is thought to be nontoxic to normal cells while killing a broad range of tumor cells. However, hepatocellular carcinoma is considered resistant to soluble TRAIL treatment. Therefore, a direct gene transfer of TRAIL to malignant cells is part of an alternative delivery strategy. We show that an adenoviral gene transfer (Ad-TRAIL) overcomes an impaired response of hepatocellular carcinoma cell lines to soluble TRAIL, but the transduction of primary human hepatocytes revealed a high number of apoptotic cells. Our data imply that Ad-TRAIL administration in vivo must either be restricted to tumor tissue or controlled by a tumor-specific promoter to avoid severe liver damage in human trials.

Adenoviruses, Human↗
PubMed2003

Sendai virus vectors as an emerging negative-strand RNA viral vector system.

The power to manipulate the genome of negative-strand RNA viruses, including the insertion of additional non-viral genes, has led to the development of a new class of viral vectors for gene transfer approaches. The murine parainfluenza virus type I, or Sendai virus (SeV), has emerged as a prototype virus of this vector group, being employed in numerous in vitro as well as animal studies over the last few years. Extraordinary features of SeV are the remarkably brief contact time that is necessary for cellular uptake, a strong but adjustable expression of foreign genes, efficient infection in the respiratory tract despite a mucus layer, transduction of target cells being independent of the cell cycle, and an exclusively cytoplasmic replication cycle without any risk of chromosomal integration. In this review we describe the current knowledge of Sendai virus vector (SeVV) development as well as the results of first-generation vector applications under both in vitro and in vivo conditions. So far, Sendai virus vectors have been identified to be a highly efficient transduction tool for a broad range of different tissues and applications. Future directions in vector design and development are discussed.

Animals↗
PubMed2003

Cell cycle independent infection and gene transfer by recombinant Sendai viruses.

A common problem for viral vectors in the field of somatic gene therapy is the dependence of an efficient cellular transduction on the cell cycle phase of target cells. An optimized viral vector system should therefore transduce cells in different cell cycle phases equally to improve transduction efficiencies. Recent observations that recombinant Sendai viruses (SeV) can infect a broad range of different tissues suggested SeV to be a good candidate for future gene therapeutic strategies in which dividing and non-dividing cells have to be reached. However, detailed data on the influence of distinct cell cycle phases on the infection of SeV or related viruses are missing. We report that synchronization of NIH 3T3 cells as well as contact inhibition of human fibroblast cells did not exhibit any negative influence on SeV infection rates. Furthermore, different attractive target tissues like human umbilical cord derived cells or primary human hepatocytes can be reached by SeV efficiently. As an important information for further cell cycle studies of paramyxoviruses we discovered surprisingly that the DNA polymerase inhibitor aphidicolin (induces a G(1)/M arrest) functions as an inhibitor of SeV but not of an adenoviral expression vector. In conclusion, the results demonstrate SeV based vector particles to be an ideal tool to reach equally cells coexisting in different cell cycle phases.

3T3 Cells↗
PubMed2003

Negative-strand RNA viral vectors: intravenous application of Sendai virus vectors for the systemic delivery of therapeutic genes.

Treatment by gene replacement is critical in the field of gene therapy. Suitable vectors for the delivery of therapeutic genes have to be generated and tested in preclinical settings. Recently, extraordinary features for a local gene delivery by Sendai virus vectors (SeVV) have been reported for different tissues. Here we show that direct intravenous application of SeVV in mice is not only feasible and safe, but it results in the secretion of therapeutic proteins to the circulation, for example, human clotting Factor IX (hFIX). In vitro characterization of first-generation SeVV demonstrated that secreted amounts of hFIX were at least comparable to published results for retroviral or adeno-associated viral vectors. Furthermore, as a consideration for application in humans, SeVV transduction led to efficient hFIX synthesis in primary human hepatocytes, and SeVV-encoded hFIX proteins could be shown to be functionally active in the human clotting cascade. In conclusion, our investigations demonstrate for the first time that intravenous administration of negative-strand RNA viral vectors may become a useful tool for the wide area of gene replacement requirements.

3T3 Cells↗
PubMed2003

Virtual bronchoscopy: comparison of different surface rendering models.

The aim of this study was to compare different representation models of surface-rendered virtual bronchoscopy. 10 consecutive patients with inoperable primary lung tumors underwent thin-section spiral computed tomography. The structures of interest, the tracheobronchial system and anatomical and pathological thoracic structures were segmented using an interactive threshold interval volume-growing segmentation algorithm and visualized with the aid of a color-coded surface rendering method. For virtual bronchoscopy, the tracheobronchial system was visualized using a triangle-surface rendering model, a shaded-surface rendering model and a transparent shaded-surface rendering model. The triangle-surface rendering model allowed optimum detailed spatial representation of the dimensions of extraluminal anatomical and pathological mediastinal structures. As the lumen of the tracheobronchial system was less well defined, the rendering model was of limited use for depiction of the airway surface. The shaded-surface rendering model facilitated an optimum assessment of the airway surface, but the mediastinal structures could not be depicted. The transparent shaded-surface rendering model provides simultaneous adequate to optimum visualization and assessment of the intraluminal airway surface and the extraluminal mediastinal structures as well as a quantitative assessment of the spatial relationship between these structures. Fast data acquisition with a multi-slice detector spiral computed tomography scanner and the use of virtual bronchoscopy with the transparent shaded-surface rendering model obviate the need for time consuming detailed analysis and presentation of axial source images by providing improved the diagnostic imaging of endotracheal and endobronchial diseases and offering a useful alternative to fiberoptic bronchoscopy.

Bronchoscopy↗
PubMed2002

Caspase-8 and Apaf-1-independent caspase-9 activation in Sendai virus-infected cells.

Apoptotic cell death is of central importance in the pathogenesis of viral infections. Activation of a cascade of cysteine proteases, i.e. caspases, plays a key role in the effector phase of virus-induced apoptosis. However, little is known about pathways leading to the activation of initiator caspases in virus-infected host cells. Recently, we have shown that Sendai virus (SeV) infection triggers apoptotic cell death by activation of the effector caspase-3 and initiator caspase-8. We now investigated mechanisms leading to the activation of another initiator caspase, caspase-9. Unexpectedly we found that caspase-9 cleavage is not dependent on the presence of active caspases-3 or -8. Furthermore, the presence of caspase-9 in mouse embryonic fibroblast (MEF) cells was a prerequisite for Sendai virus-induced apoptotic cell death. Caspase-9 activation occurred without the release of cytochrome c from mitochondria and was not dependent on the presence of Apaf-1 or reactive oxygen intermediates. Our results therefore suggest an alternative mechanism for caspase-9 activation in virally infected cells beside the well characterized pathways via death receptors or mitochondrial cytochrome c release.

Animals↗