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Biomedical subjects

U Fischer

Publications and source records attributed to U Fischer.

At least 55 records · Page 3Linked to original sources
PubMed2002

[Quality management in a radiology department].

PURPOSE: To increase the quality of internal and external interactions (patients, clinical colleagues, technicians, radiologists) in a department of radiology. METHOD: Accompanied by a well-experienced adviser workshops have been performed dealing with different topics like "contact to patients," "performance of the radiological report and interaction with the referring colleague" or "research and teaching." A catalogue of different actions was defined to reduce hindrances within the internal and external work-flow. RESULTS: A total number of 53 actions was defined and related to different persons who were responsible for the realisation of the measures within a time interval. Six months after starting the quality management 46 (86%) of the defined actions were realised successfully, and another 4 (8%) measures were still running. There was a moderate increase of satisfaction of the patients and clinical colleagues considering the waiting time. CONCLUSIONS: A quality management in a radiological department allows an optimisation of the internal and external interactions. However, the guidance of a well-experienced adviser is as essential as the continuous control of successful finished measures.

Education↗
PubMed2002

[Soft copy versus hard copy findings in digital mammography].

The advantages of full field digital mammography are the excellent and reliable image quality and the reduction of radiation exposure. Image acquisition and display are decoupled in digital mammography allowing for optimization of both independently. Image displays are currently either hardcopy produced with a laser printer or softcopy using a computer monitor. Since the amount of data is high the hardware and software must meet specific technical specifications. The diagnostic accuracy of softcopy and hardcopy interpretation is comparable if a high resolution laser printer and a high quality workstation with high spatial and contrast resolution monitors are used. However, using film display the potential benefits of digital mammography in terms of manipulation of the data is lost. Additional diagnostic benefits might be gained by the combination of softcopy display and computer assisted diagnosis (CAD) and telemammography.

Breast Neoplasms↗
PubMed2002

[Digital full field mammography: comparison between radiographic direct magnification and digital monitor zooming].

PURPOSE: Our goal was to compare digital magnification mammograms with images zoomed from the digital contact mammogram in patients with microcalcifications. PATIENTS AND METHODS: Fifty-five patients with 57 microcalcification clusters were evaluated with a FFDM system (Senographe 2000D, GE). In addition to a digital contact mammogram, a digital direct magnification mammogram (factor 1.8 [MAG1.8]) and an image zoomed from the contact mammogram with a magnification factor of 1.8 [ZOOM1.8] were obtained in each patient. The image quality (perfect = 5 points to inadequate = 1 point) and the characterization of microcalcifications (BI-RADS 2-5) were evaluated by 4 readers. The results were compared to histopathologic findings in 35 patients (37 lesions) and follow-up in 20 patients. RESULTS: Histopathology revealed 16 benign and 21 malignant lesions. 20 patients had benign changes verified by long-term follow-up. Image quality of direct magnification FFDM was assessed superior (4.44 points) to zoomed images (4.14 points). Sensitivity was superior for direct magnification (97.5%) in comparison to the zoomed images (96.3%). However, specificity (MAG1.8: 34.3%, ZOOM1.8: 40%), PPV (MAG1.8: 47.5%, ZOOM1.8: 49.8%) and accuracy (MAG1.8: 58.1%, ZOOM1.8: 61.2%) were better with zooming technique. Deviation steps from best BI-RADS assessment were 0.45 for MAG1.8 and 0.44 for ZOOM1.8. CONCLUSIONS: In patients with mammographic microcalcifications, monitor zooming of the digital contact mammogram is equivalent to direct magnification FFDM. Therefore, monitor zooming allows a reduction of the radiation exposure and an optimization of the work-flow.

Breast Diseases↗
PubMed2002

Polypoid endometrial adenomyoma in a postmenopausal woman, mimicking cervical cancer, associated with ovarian thecoma.

PURPOSE: Atypical polypoid adenomyoma (APA) usually occurs in premenopausal women and arises from the endometrium. APAs protruding into the external os may lead to diagnostic problems. CASE: We present a case of APA in a 62-year-old postmenopausal woman, prolapsing through the external os, clinically mimicking cervical cancer FIGO IB2 (4.5 cmx3 cmx3 cm). Histologically the tumor was composed of endometrioid-like with slight cellular atypia and endocervical-type mucinous glands admixed with smooth muscle bundles, exhibiting low Ki-67 antigen immunostaining. The the left adnexa contained an ovarian thecoma. CONCLUSIONS: To the best of our knowledge, this is the first case of APA in a postmenopausal woman, mimicking cervical cancer and associated with ovarian thecoma. Pathogenetically it is proposed, that hyperestrogenism and, in the present case accompanied by progestin production of questionable source, may play an important role in the development of APAs with the admixture of endometrial and endocervical glands.

Adenomyoma↗
PubMed2002

[Indications for percutaneous stereotactic vacuum core biopsy of the breast].

As a consequence of technical improvements and an increased number of investigations in asymptomatic patients, more and more suspicious lesions are being detected in mammography. These lesions can be evaluated using different biopsy techniques. In comparison to open biopsy, stereotactic methods require less costs and time, and reduce morbidity. The introduction of the vacuum core biopsy method allowed the excision of suspicious areas through a single needle insertion. In the current literature, however, the indications for vacuum core biopsy are being discussed controversely. This article includes an introduction of this specific technique, a presentation of the BI-RADS (Breast Imaging Reporting and Data System) categories and an overview of the literature of the indications for use of the vacuum system. The "pros and cons" of vacuum core biopsy will be discussed in comparison with the alternative biopsy methods.

Biopsy↗
PubMed2002

Cytotoxic T cell function in fish.

Fish possess immunoglobulins, major histocompatibility complex (MHC), T-cell receptors, and lymphocyte populations analogous to B and T cells and can evoke specific immune responses against a variety of antigens. However, T-cell subsets have yet to be demonstrated and the information on cell-mediated immunity is limited. Here we briefly review our recent studies on specific cell-mediated immunity, particularly on cytotoxic T-cell function employing isogeneic fish and cell lines. Analyses of the graft-versus host reaction (GVHR) and cell-mediated cytotoxicity (CMC) against allogeneic erythrocytes or cell lines show alloantigen-specific cytotoxicity in clonal ginbuna crucian carp. We also describe specific cytotoxicity against virus-infected cells using clonal ginbuna and a syngeneic cell line. Lastly, we report MHC-restriction in CMC against virus-infected cells using homozygous clonal rainbow trout and trout cell line which share the same MHC class I allele. These studies on CMC strongly suggest the presence of antigen specific cytotoxic T cells in teleosts and functional similarities between the immune systems of fish and higher vertebrates. Experimental model systems established in these studies can be applied to the investigation of protective antigens to induce cell-mediated immunity for the development of fish vaccines.

Animals↗
PubMed2002

Systemic activation of the immune system during ganciclovir treatment following intratumoral herpes simplex virus type 1 thymidine kinase gene transfer in an adolescent ependymoma patient.

During ganciclovir treatment of an adolescent ependymoma patient two weeks after intracranial implantation of HSVtk retroviral vector producer cells, increasing numbers of peripheral T- and B-cells were found as well as enhanced T-cell activation and elevated serum levels of interleukin 12 and soluble Fas ligand. These findings suggest the systemic activation of the immune system during ganciclovir treatment in our patient. The induction of an immune response by HSVtk/ganciclovir supports the concept of an anti-tumor vaccination effect by prodrug activating gene therapy systems and may open new promising perspectives for enhancing therapeutic efficiency by combined prodrug activating and immunological gene therapy strategies.

Adolescent↗
PubMed2002

Average glandular dose with amorphous silicon full-field digital mammography - Clinical results.

PURPOSE: Determination of average glandular dose with a full-field digital mammography system using a flat-panel X-ray detector based on amorphous silicon technology for a large group of patients. MATERIAL AND METHODS: The patient group includes women who were examined in a 4-month period with the digital mammographic system Senographe 2000D. The number of women was 591 and the number of exposures was 1116; only cranio-caudal projections were considered. Various quantities, including entrance surface air kerma, tube loading, and compressed breast thickness, were determined during actual mammography. Average glandular dose was determined using conversion factors g for standard breast composition. RESULTS: The mean average glandular dose was 1.51 mGy (0.66 - 4.05 mGy) for a single view. The mean compressed breast thickness was 55.7 mm. The mean age of patients was 55 years (34 - 81 years). CONCLUSION: The results demonstrate that full-field digital mammography with a flat-panel detector based on amorphous silicon needs about 25 % less dose in comparison with conventional screen-film mammography.

Adult↗
PubMed2002

Clinical relevance of urokinase-type plasminogen activator and its inhibitor type 1 (PAI-1) in squamous cell carcinoma of the uterine cervix.

OBJECTIVE: The expression of uPA and PAI-1 as parameters of tumour-associated proteolysis has been implicated in the process of tumour cell invasion and the metastatic process. However, there is limited information on the impact of these parameters in cervical carcinoma. METHODS: Quantitative levels for uPA (n = 114) and PAI-1 (n = 103) were researched in operatively treated, surgically staged squamous cell cancer of the uterine cervix, using an ELISA-technique. Results were assessed regarding their impact in predicting pelvic lymph nodes metastases, tumour recurrence rate and recurrence free survival (RFS) using uni- and multivariate analysis. RESULTS: Median levels of both parameters were significantly higher in tumour tissue than in normal cervical tissue (p < 0.001). Detection of uPA gave no useful prognostic information. PAI-1 concentration showed a positive correlation with advanced tumour stage (p = 0.008), but no significant correlation with nodal status (pN0: 2.6 vs. pN1: 4.0 ng/mg protein; p = 0.092). Using a cut-off level of 2.4 ng/mg protein, patients with elevated PAI-1 levels demonstrated reduced RFS (45.9 versus 52.9 months; p = 0.1). Multivariate analysis, including nodal status, tumour stage, lymphovascular space involvement and grading failed to demonstrate any prognostic impact of uPA and PAI-1. CONCLUSIONS: The results indicate, that PAI-1 expression is of some prognostic impact in cervical cancer, indicating an association of elevated PAI levels with local tumour progression and reduced recurrence-free survival.

Adult↗
PubMed2001

Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln.

Seven Sm proteins, termed B/B', D1, D2, D3, E, F, and G, assemble in an ordered manner onto U snRNAs to form the Sm core of the spliceosomal snRNPs U1, U2, U4/U6, and U5. The survival of motor neuron (SMN) protein binds to Sm proteins and mediates in the context of a macromolecular (SMN-) complex the assembly of the Sm core. Binding of SMN to Sm proteins is enhanced by modification of specific arginine residues in the Sm proteins D1 and D3 to symmetrical dimethylarginines (sDMAs), suggesting that assembly might be regulated at the posttranslational level. Here we provide evidence that the previously described pICln-complex, consisting of Sm proteins, the methyltransferase PRMT5, pICln, and two novel factors, catalyzes the sDMA modification of Sm proteins. In vitro studies further revealed that the pICln complex inhibits the spontaneous assembly of Sm proteins onto a U snRNA. This effect is mediated by pICln via its binding to the Sm fold of Sm proteins, thereby preventing specific interactions between Sm proteins required for the formation of the Sm core. Our data suggest that the pICln complex regulates an early step in the assembly of U snRNPs, possibly the transfer of Sm proteins to the SMN-complex.

Animals↗
PubMed2001

Preoperative local MRI-staging of patients with a suspected pancreatic mass.

The aim of this study was to define the value of MRI of the pancreas for preoperative local staging of patients with a suspected pancreatic mass. Ninety-four patients (41 women, 53 men; age range 32-87 years) with a suspected pancreatic tumor underwent preoperative staging with MRI on a 1.5-T system. The MRI protocol included breath-hold MR cholangiopancreatography in turbo spin-echo technique, biphasic contrast-enhanced 3D MR angiography, and MRI of the upper abdomen with breath-hold T2-weighted half-Fourier acquired single-shot turbo spin-echo and T1-weighted fast-low-angle-shot (pre- and postcontrast) sequences. Data were collected prospectively and analyzed by two radiologists in agreement modality. Evaluation criteria were vascular involvement, resectability, and a characterization benign vs malignant. Results were compared to histopathology in 78 patients. Sixteen patients were followed-up. In 74 of 94 patients a solid tumor or an inflammation of the pancreas ( n=62) or the papilla ( n=12) was detected. In this group, MRI had a sensitivity of 98%, a specificity of 92%, and an accuracy of 96% in the characterization of malignant tumors. Regarding only the solid tumors, the positive predictive value of MRI was 87% with respect to resectability. Other pathologic findings included adenoma or inflammation of the duodenum ( n=5), carcinoma or benign stenosis of the choledochus duct ( n=7) and carcinoma of the gall bladder ( n=2). In 6 patients MRI did not depict any pathologic findings, and follow-up confirmed this interpretation. Magnetic resonance imaging allows a local preoperative staging in patients with suspected pancreatic tumor. Limitations, however, concern to the diagnostics of peritoneal and/or liver metastases.

Adult↗
PubMed2001

Direct interaction of the spinal muscular atrophy disease protein SMN with the small nucleolar RNA-associated protein fibrillarin.

Disruption of the survival motor neuron (SMN) gene leads to selective loss of spinal motor neurons, resulting in the fatal human neurodegenerative disorder spinal muscular atrophy (SMA). SMN has been shown to function in spliceosomal small nuclear ribonucleoprotein (snRNP) biogenesis and pre-mRNA splicing. We have demonstrated that SMN also interacts with fibrillarin, a highly conserved nucleolar protein that is associated with all Box C/D small nucleolar RNAs and functions in processing and modification of rRNA. Fibrillarin and SMN co-immunoprecipitate from HeLa cell extracts indicating that the proteins exist as a complex in vivo. Furthermore, in vitro binding studies indicate that the interaction between SMN and fibrillarin is direct and salt-stable. We show that the glycine/arginine-rich domain of fibrillarin is necessary and sufficient for SMN binding and that the region of SMN encoded by exon 3, including the Tudor domain, mediates the binding of fibrillarin. Tudor domain missense mutations, including one found in an SMA patient, impair the interaction between SMN and fibrillarin (as well as the common snRNP protein SmB). Our results suggest a function for SMN in small nucleolar RNP biogenesis (akin to its known role as an snRNP assembly factor) and reveal a potential link between small nucleolar RNP biogenesis and SMA.

Amino Acid Sequence↗
PubMed2001

Contrast-enhanced MR angiography of abdominal vessels: is there still a role for angiography?

The purpose of this review article is to describe recent advantages in contrast-enhanced (CE) three-dimensional (3D) magnetic resonance angiography (MRA) in comparison with other vascular imaging techniques, and to discuss their current clinical applications for the imaging of abdominal vessels. Principles and technical considerations are presented and clinical applications are reviewed for different vascular diseases. In ruptured aortic aneurysms and acute dissections CT is the method of first choice. Contrast-enhanced 3D MRA can be well used for therapeutic planning and follow-up in patients with stable disease. A comprehensive MR examination including CE 3D MRA, MR urography and MR nephrogram has the potential to replace the conventional studies for the evaluation of renal vascular disease. It is an accurate method for imaging the origins of coeliac and superior mesenteric arteries, although the image resolution is too low for reliable assessment of the inferior mesenteric artery. Contrast-enhanced 3D MRA has emerged as the method of choice for studying the portal venous system in liver transplant recipients, in patients with portal hypertension and in cases with abdominal tumours for preoperative evaluation. Additional non-invasive flow measurements are useful in monitoring portal hypertension. The abdominal veins can be well imaged using unenhanced MR techniques. Imaging may be facilitated with intravascular contrast media. Contrast-enhanced 3D MRA can replace intra-arterial DSA for diagnosis, therapy planning and follow-up in patients with abdominal vascular disease. Catheter-based arteriography will still be used for interventional procedures such as percutaneous transluminal angioplasty, stent placement and embolisation.

Abdomen↗
PubMed2001

Expression, cellular distribution and protein binding of the glioma amplified sequence (GAS41), a highly conserved putative transcription factor.

The glioma amplified sequence 41 (GAS41) was previously isolated by microdissection mediated cDNA capture from the glioblastoma multiforme cell line TX3868 and shown to be frequently amplified in human gliomas. We determined the complete cDNA sequence of the GAS41 gene, demonstrated that the GAS41 protein is evolutionarily conserved, specifically at the N-terminus, and identified the yeast transcription factor tf2f domain within the GAS41 sequence. A human multiple-tissue Northern blot revealed ubiquitous expression of GAS41 with the highest expression in human brain. After generating polyclonal antibodies we found GAS41 protein expression in the nucleus of the TX3868 cell line by Western blot analysis and immunofluorescence microscopy. The nuclear localization was confirmed for several human tumors including gliomas of different grades of malignancy. In neuroblastoma however, GAS41 was found in the nucleoli but not in the nucleoplasm. Yeast two-hybrid screening of the TX3868 cell line identified the nuclear mitotic apparatus protein (NuMA), the KIAA1009 protein, and prefoldin subunit 1 (PFDN1) as potential interacting partners of GAS41. We generated a polyclonal antibody against the KIAA1009 protein and we demonstrated that the KIAA1009 protein is a nuclear protein, which appears to be co-localized with the GAS41 protein and NuMA.

Amino Acid Sequence↗
PubMed2001

PHF3-specific antibody responses in over 60% of patients with glioblastoma multiforme.

Glioblastoma multiforme (GBM), a malignant astrocytic tumour, represents the most frequent tumour of the human brain. Nevertheless, its molecular pathology is not well understood. We utilized the immune system, which contributes to cancer protection, to help identify new GBM-related genes. By screening a human GBM cDNA library with autologous patient serum (SEREX-approach), we isolated a gene termed PHF3 (PHD finger protein 3). The gene product of PHF3 is immunogenic in GBM as tested in an allogenic patient serum screening demonstrating antibodies in 24 of 39 (61.53%) sera, whereas none of the 14 healthy persons had antibodies against PHF3. While previous SEREX studies revealed allogenic antibody responses up to 40%, our results for PHF3 represent the highest reported rate for a specific antibody response. We show that GBM patients with an antibody response against PHF3 show significant better survival than patients without PHF3-specific antibodies. Because the amino acid sequence of PHF3 contains a PHD finger (also termed LAP motif), a TFIIS homology, a proline rich region and nuclear localization signals, it supposedly functions as a transcription factor. A polyclonal antibody generated against PHF3 shows nuclear expression in most investigated formalin-fixed, paraffin embedded tissues. In GBM, PHF3 expression is concentrated in cells surrounding necroses.

Adult↗
PubMed2001

SMNrp is an essential pre-mRNA splicing factor required for the formation of the mature spliceosome.

SMNrp, also termed SPF30, has recently been identified in spliceosomes assembled in vitro. We have functionally characterized this protein and show that it is an essential splicing factor. We show that SMNrp is a 17S U2 snRNP-associated protein that appears in the pre-spliceosome (complex A) and the mature spliceosome (complex B) during splicing. Immunodepletion of SMNrp from nuclear extract inhibits the first step of pre-mRNA splicing by preventing the formation of complex B. Re-addition of recombinant SMNrp to immunodepleted extract reconstitutes both spliceosome formation and splicing. Mutations in two domains of SMNrp, although similarly deleterious for splicing, differed in their consequences on U2 snRNP binding, suggesting that SMNrp may also engage in interactions with splicing factors other than the U2 snRNP. In agreement with this, we present evidence for an additional interaction between SMNrp and the [U4/U6.U5] tri-snRNP. A candidate that may mediate this interaction, namely the U4/U6-90 kDa protein, has been identified. We suggest that SMNrp, as a U2 snRNP-associated protein, facilitates the recruitment of the [U4/U6.U5] tri-snRNP to the pre-spliceosome.

Animals↗
PubMed2001

Co-regulation of survival of motor neuron (SMN) protein and its interactor SIP1 during development and in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by the degeneration of motor neurons in the spinal cord. The disease is caused by mutations of the survival of motor neuron 1 gene (SMN1), resulting in a reduced production of functional SMN protein. A major question unanswered thus far is why reduced amounts of ubiquitously expressed SMN protein specifically cause the degeneration of motor neurons without affecting other somatic cell types. In a first attempt to address this issue we have investigated the Smn interacting protein 1 (Sip1), with an emphasis on its developmental expression and subcellular distribution in spinal motor neurons in relation to Smn. By confocal immunofluorescence studies we provide evidence that a significant amount of Smn does not co-localize with Sip1 in neurites of motor neurons, indicating that Smn may exert motor neuron-specific functions that are not dependent on Sip1. Sip1 is highly expressed in the spinal cord during early development and expression decreases in parallel with Smn during postnatal development. Strikingly, reduced production of Smn as observed in cell lines derived from SMA patients or in a mouse model for SMA coincides with a simultaneous reduction of Sip1. The finding that expression of Sip1 and Smn is tightly co-regulated, together with the unique localization of Smn in neurites, may help in understanding the motor neuron-specific defects observed in SMA patients.

Amino Acid Sequence↗