Biomedical subjects

U Fischer

Publications and source records attributed to U Fischer.

At least 91 records · Page 5Linked to original sources

PubMed2001

[Histopathological prognostic factors in primary surgically treated cervix carcinoma].

OBJECTIVE: Standardised morphologic evaluation of radical hysterectomy specimens in primary surgically treated cervical cancer improves the selection of cases for adjuvant therapy and the precision for prognosis and may be helpful in quality control of oncologic surgery. MATERIAL AND METHODS: Following standardised macroscopic evaluation [29] the original histologic slides of all surgically treated patients with cervical cancer were searched for tumor type, histologically proven pelvic lymph node metastases (PLM), lympho-vascular space involvement (LVSI), tumor differentiation (grading), peritumoral inflammatory response, pattern of cervical wall involvement and relative depth of invasion. The results were compared with follow up. RESULTS: The frequency of patients up to 35th year of age was 28.8% and increased between 1979 and 1993 of about 10% (p > 0.05). Younger women represented more pT1 b1-tumors (55.6% vs. 47%), but without statistic significance. Contrary to advanced tumor stage and the presence of PLM, adenocarcinomatous histology (5.1% of all cases) was not associated with poor prognosis. Patients with pT1b-tumors of more than 4 cm largest extension (pT1 b2) showed a twice-fold frequency of PLM and pelvic recurrences. Five-year survival rate (5-Y-SR) decreased (82.7% vs. 64.9%) and more patients died of cancer (p = 0.005, each). Diffuse infiltration pattern was accompanied with higher rate of tumor recurrency and a shortening of 5-Y-SR compared with pushing borders at the front of infiltration, 38% versus 13.7% and 45.4% versus 75.2%, respectively. Similar was seen in poorly differentiated tumors (G3), compared with well differentiated (G1) carcinomas (recurrency: 15.1% vs. 27.5%, 5-Y-SR 75.7% vs. 59.3%; p < 0.05). Cases with the presence of LVSI, absence of peritumoral inflammatory response and deep cervical infiltration (> 66%) were accompanied with poor prognostic outcome. CONCLUSIONS: In patients with primary surgically treated cervical cancer prognostic risk evaluation can be made by standardised histopathologic handling of hysterectomy specimens. Cases with early cervical cancer and high tumor load (pT1 b2), advanced staged disease (pT2 b), histologically proven PLM, LVSI, poor tumor differentiation (G3), absence of peritumoral inflammatory response and deep cervical wall infiltration are associated with poor prognostic outcome. Patients with these morphologic patterns, which can be established by clinical examination and diagnostic biopsy, represent the clientel for adjuvant or neoadjuvant therapy.

Adenocarcinoma↗

PubMed2001

[Stereotactic vacuum core biopsy of clustered microcalcifications classified as B1-RADS 3].

PURPOSE: Evaluation of stereotactic vacuum core biopsy of clustered microcalcifications categorized as BI-RADS 3. MATERIAL AND METHODS: 86 patients with microcalcifications BI-RADS 3 (probably benign, < 3% malignant) underwent a stereotactic vacuum core biopsy (Mammotome, Fa. Ethicon Endo-Surgery Breast Care) using a digital stereotactic unit (Mammotest, Fa. Fischer Imaging). The removal of the calcifications was judged by two radiologists in consensus and classified as complete (100%), major (55-99%) or incomplete (< 50%). RESULTS: 4/86 patients could not be evaluated by vacuum core biopsy due to the localization of the microcalcifications close to the skin or lack of detection. In 40/82 cases a complete, in 38/82 a major, and in 4/82 a incomplete removal was achieved. Histology revealed 67 cases of fibrocystic changes, 4 papillomas, 4 fibroadenomas, 4 cases of atypical ductal hyperplasia (ADH), and 3 ductal carcinomas in situ (DCIS), one of these with a minimal-invasive tumor component. Patient with ADH were advised to undergo surgical biopsy. Histology revealed complete removal. 7 patients had complications or side-effects. CONCLUSIONS: Percutaneous vacuum core biopsy is a reliable minimal-invasive diagnostic method to come to the final diagnosis in patients with clustered microcalcifications categorized BI-RADS 3. However, if malignancy is proven (about 4% of our cases) an open biopsy is necessary.

Adult↗

PubMed2001

[Experimental evaluation of vessel diameter from 0.3 to 8 mm in CE MR angiography].

PURPOSE: To evaluate the detection rate of vascular stenosis in contrast-enhanced 3D MR angiography using a flow phantom. MATERIAL AND METHODS: The examinations were performed on a 1.5 T whole body imaging system (Magnetom Symphony/Quantum) with 30 mT/m gradient field strength using a body-phased-array coil. Different 3D sequences (TR/TE/FA < 5 ms/< 2 ms/25 degrees ) with slice thicknesses ranging from 0.67 to 1.25 mm were applied. A gelantine-filled plastic cylinder with PVC tubes of 8 mm diameter was used as a vascular phantom. The tubes had concentric and excentric stenoses (50 - 90 %) of different lengths. For the detection of different vessel diameters another phantom with 0.3 - 8 mm silicon tubes was used. Both systems were flushed with a solution of Gd-DTPA (0.15 mmol/l) and saline at flow rates from 50 to 200 cm/s. The phantoms were positioned 0 degrees, 45 degrees, and 90 degrees towards the z-axis. RESULTS: The degree of stenosis was under- and overestimated in less than 10 %. The sequence with the highest spatial resolution provided the best results. Detection and evaluation of tubes >/= 2 mm proved to be reliable. CONCLUSION: Contrast-enhanced 3D MR angiography provides an almost exact evaluation of the degree of stenosis in the phantom study. Evaluation of vessel diameters < 2 mm is not possible.

Arterial Occlusive Diseases↗

PubMed2001

[Myxoid uterine leiomyoma with focal lymphangioma-like pattern].

Myxoid leiomyomas of the uterus are uncommon. They are characterised by a myxoid stroma, no mitotic activity and a myogenic phenotype. We present a case with focal lymphangioma-like pattern. The solid compartiment showed positive immunoreactivity with muscular markers and but no CD 34-immunostaining. Contrary, the endothelial-like cells of the cystic part were positive with antibodies against CD 34, CD 31 and factor VIII, indicating vascular differentiation. The lack of infiltrative growth patterns excluded myxoid leiomyosarcoma as the major differenzial diagnosis.

Adult↗

PubMed2001

p53 in surgically treated and pathologically staged cervical cancer: correlation with local tumor progression, but not with lymphatic spread.

There is only limited information about the prognostic value of p53 immunostaining in cervical cancer. The purpose of this study was to assess the clinical significance of p53 and prognosis in operatively treated cervical carcinoma. A hundred and fourteen primary surgically treated cervical carcinomas (CX) were obtained from the so called Wertheim Archive in the Department of Obstetrics and Gynecology at the University of Leipzig. These included 105 squamous cell cancer (SCC) and nine adenocarcinomas (AC). No cases received neoadjuvant therapy. For immunohistochemical analysis, the cases were tested with the monoclonal antibody DO-7 (DAKO Diagnostics, Denmark). Two hundred tumor cell nuclei were counted for positive nuclear immunostaining, regardless of staining intensity. Cases were stated as positive when a minimum of 10% nuclei showed positive staining. Fresh frozen tissue was available from 21 CX for p53-mutation analysis (exons 4-9) using PCR-based amplification and SSCP-analysis. Of the squamous cell cancers (SCC), 63.8% showed positive nuclear p53-immunostaining; adenocarcinomas (AC) were completely negative (P = 0.0000, Chi2-test). Stage-by-stage analysis revealed no differences in p53-expression. However, combining pT1b- and pT2-cases, the difference in positive immunostaining reached statistical significance (44.4% vs. 71.7%; P = 0.007). There were no differences in p53-reactivity regarding the presence of pelvic lymph node metastases, tumor grading, relapse-free survival and tumor recurrence. In addition, only 5% of CX with positive p53-immunostaining showed genomic alterations in mutational analysis. p53-immunoreactivity showed significant correlation with local tumor progression but not with lymphatic spread, lacking any prognostic impact in surgically treated cervical cancer. There is no correlation of p53-immunostaining with the occurrence of p53-gene mutations in cervical cancer.

Adenocarcinoma↗

PubMed2001

PHF3 expression is frequently reduced in glioma.

Glioblastoma is the most frequent brain tumor and accounts for approximately 50--60% of all astrocytic tumors. Many chromosome alterations have been described in glioblastoma, but only for a few alterations were the genes identified and linked to genetic pathways in glioblastoma development. To contribute to the identification of novel genes involved in glioblastoma development we used a combined immunological and molecular screening approach. Here we report the identification and expression analysis of a novel gene from human chromosome 6q12 that is considered to be the third member of a family of PHD finger containing genes and is termed PHF3. PHF3 is ubiquitously expressed in normal tissues including brain, but its expression is significantly reduced or lost in glioblastoma, glioblastoma cell lines, anaplastic astrocytomas and astrocytomas. The PHF3 protein sequence contains several protein motifs frequently found in transcription factors. One of those motifs is a PHD finger, also termed LAP motif and known to bind large portions of DNA. Another region of the protein revealed a high homology to the transcription factor TFIIS, especially to a region that is necessary for the Polymerase II binding properties of TFIIS. Combining these results, PHF3 is a novel member of a large class of regulatory proteins containing a LAP motif, and loss of its expression in glioblastoma may contribute to glioma development.

Adult↗

PubMed2001

Localization of alpha(2)-macroglobulin receptor/low-density lipoprotein receptor in third-trimester human placentas: a preliminary immunohistochemical study.

The alpha(2)-macroglobulin receptor/low-density lipoprotein receptor-related protein (alpha(2)-M-R/LRP) is involved in a variety of transcellular transportations, e.g. of apolipoprotein E, and represents an inhibitor of proteinases. After creation of monoclonal antibodies of the alpha- and beta-subunits of the alpha(2)-M-R/LRP and its receptor-associated protein, we have tested their distribution in five 3rd-trimester placentas, using cryosections, immunohistochemically and by immunofluorescence. All three monoclonal antibodies showed positive staining in villous and extravillous cytotrophoblasts and intravillous vessels, but not in syncytiotrophoblasts. Thus, alpha(2)-M-R/LRP plays a possible role in the transplacental nutritional transportation process. It is necessary to search the distribution of alpha(2)-M-R/LRP under pathological conditions, like fetal growth retardation and preeclampsia.

Female↗

PubMed2001

Novel tankyrase-related gene detected with meningioma-specific sera.

In many meningiomas, alterations of chromosome 22 can be found, and the NF2 (neurofibromatosis type 2) gene, in particular, is of great interest as a putative gene involved in meningioma. Because the NF2 gene is not mutated in all meningiomas, additional genes may be involved. Instead of looking for alterations directly at the DNA level, we used the immune response of meningioma patients to identify immunogenic antigens that may be associated with the disease. We screened a fetal brain cDNA expression library with sera pools from different patients bearing meningioma classified according to the three WHO grades, using the serological identification of antigens by recombinant expression cloning immunological screening method. Here, we report the finding of a new tankyrase-related protein. We found 16 overlapping clones with homologies to tankyrase when we screened the library with the common-type meningioma sera pool and 2 such clones when we screened the library with the atypical meningioma sera. The anaplastic meningioma sera did not identify any tankyrase-related clones. We tested some of the newly identified clones with 13 single sera, 6 of which (37.5%) reacted positively with the tankyrase-related clones. In addition, we screened the tankyrase-related clone with six sera pools from individuals without obvious disease. Although 1 of 24 (4.2%) normal sera reacted with the tankyrase-related clone, we found a striking difference in the frequency of reactivity to this clone by sera from patients bearing tumors corresponding to the three WHO meningioma grades; common-type sera was the most frequently reactive. Northern blot analysis demonstrates expression of the novel tankyrase gene in two common-type meningiomas from patients with immune response.

Amino Acid Sequence↗

PubMed2001

Amplification and expression of splice variants of the gene encoding the P450 cytochrome 25-hydroxyvitamin D(3) 1,alpha-hydroxylase (CYP 27B1) in human malignant glioma.

PURPOSE: Recently, we reported the isolation of six novel genes termed glioma-amplified sequences (GASs) from the glioblastoma cell line TX3868 using microdissected mediated cDNA capture (U. Fischer et al., HUM: MOL: GENET:, 5: 595-600, 1996). The aim of this study was to further characterize the gene GAS89. EXPERIMENTAL DESIGN: To determine the amplification frequency, we performed comparative PCR studies and Southern blot hybridization experiments. To identify full-length clones of GAS89 we screened a HybriZAP library. Reverse transcription-PCR was performed to isolate splice variants and to determine expression levels. RESULTS: We identified for the gene GAS89 an amplification frequency of 25% in 28 examined glioblastoma multiforme samples. Screening a HybriZAP library, we isolated an incomplete gene sequence showing identity with the gene for 25-hydroxyvitamin D(3) 1,alpha-hydroxylase. Different full-length clones were then isolated using PCR primers chosen from the 3'- and 5'-untranslated regions. As determined by sequencing, the clones represent various splice variants of the 25-hydroxyvitamin D(3) 1,alpha-hydroxylase gene. The clones encode truncated proteins but also one potentially functional enzyme variant. Reverse transcription-PCR studies revealed overexpression of several variants in glioblastoma samples with GAS89 amplification in comparison with normal brain RNA and glioblastoma without GAS89 amplification. CONCLUSIONS: This is the first report of gene amplification for 25-hydroxyvitamin D(3) 1,alpha-hydroxylase and the appearance of mRNA splice variants in glioblastoma multiforme. The endogenous expression of the 25-hydroxyvitamin D(3) 1,alpha-hydroxylase gene and the appearance of alternative splice variants reveal a new feature of the molecular pathogenesis of glioblastoma and may represent a new target for glioma therapy.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

PubMed2001

[Conventional or digital mammography].

Digital techniques have been applied in many fields of diagnostic radiology, but they were not accepted in mammography. The technological base of direct digital mammography was the development of CCD-chips. Clinical experiences with this system are promising and may lead to replacement of conventional techniques in the future. With intraindividual correlation studies it was shown that microcalcifications were detected better than with conventional techniques. Patients' dose is equal with both system and the reporting time could be reduced. Moreover, digital mammography is important for the use of software programmes of computer assisted diagnosis (CAD).

Breast Neoplasms↗

PubMed2000

Characterization of a nuclear 20S complex containing the survival of motor neurons (SMN) protein and a specific subset of spliceosomal Sm proteins.

Spinal muscular atrophy (SMA) is a neurodegenerative disease of motor neurons caused by reduced levels of functional survival of motor neurons (SMN) protein. Cytoplasmic SMN directly interacts with spliceosomal Sm proteins and facilitates their assembly onto U snRNAs. Nuclear SMN, in contrast, mediates recycling of pre-mRNA splicing factors. In this study, we have addressed the function of SMN in the nucleus. We show that a monoclonal antibody directed against SMN inhibits pre-mRNA splicing. Interestingly, the mode of inhibition suggests a novel role for SMN in splicing that occurs prior to, or in addition to, its role in recycling. Using biochemical fractionation and anti-SMN immunoaffinity chromatography, we identified two distinct nuclear SMN complexes termed NSC1 and NSC2. The biochemical properties and protein composition of NSC1 were determined in detail. NSC1 migrates in sucrose gradients as a U snRNA-free 20S complex containing at least 10 proteins. In addition to SMN, these include the SMN-interacting protein 1 (SIP-1), the putative helicase dp103/Gemin3, the novel dp103/Gemin3-interacting protein GIP1/Gemin4 and three additional proteins with apparent masses of 43, 33 and 18 kDa, respectively. Most surprisingly, NSC1 also contains a specific subset of spliceosomal Sm proteins. This shows that the SMN-Sm protein interaction is not restricted to the cytoplasm. Our data imply that nuclear SMN affects splicing by modulating the Sm protein composition of U snRNPs.

Amino Acid Sequence↗

PubMed2000

Oral immunisation of wild boar against classical swine fever: evaluation of the first field study in Germany.

The effectiveness of oral immunisation of wild boar against classical swine fever (CSF) was studied in a field trial in Lower Saxony for two years, from 1993 to 1995. This field study was performed in an area of ca. 270 km(2)50% of young boars did not feed on vaccine baits nor become immunised. Therefore, an intensive hunting of this age group is a necessary adjunct to the use of oral vaccination. After the third immunisation period, no virus was detected in the areas where oral immunisation took place.

Administration, Oral↗

PubMed2000

The Schizosaccharomyces pombe protein Yab8p and a novel factor, Yip1p, share structural and functional similarity with the spinal muscular atrophy-associated proteins SMN and SIP1.

The motor neuron disease spinal muscular atrophy (SMA) is caused by reduced levels of functional survival of motor neurons (SMN) protein. Previous studies have shown that SMN binds to the SMN-interacting protein SIP1 and mediates the assembly of spliceosomal U snRNPs in the cytoplasm. In addition, a nuclear function for SMN in pre-mRNA splicing has recently been proposed. Here, we describe the analysis of the Schizo-saccharomyces pombe protein Yab8p and provide evidence that it is structurally and functionally related to SMN found in higher eukaryotes. We show that Yab8p interacts via its N-terminus with a novel protein termed Yip1p. Importantly, Yip1p exhibits homology to SIP1, and the mode of binding to Yab8p is remarkably similar to the SMN-SIP1 interaction. Hence, Yip1p is likely to be the homologue of SIP1 in S.pombe. Yab8p and Yip1p localize predominantly in the nucleus. Genetic studies demonstrate that Yab8p is essential for viability. Strikingly, suppression of YAB8 expression in a conditional knock-out strain causes nuclear accumulation of poly(A) mRNA and inhibition of splicing. These data identify Yab8p as a novel factor involved in splicing and suggest that Yab8p exerts a function similar or identical to the nuclear pool of SMN. Our studies provide a model system to study the cellular function of SMN in yeast, and should help in understanding the molecular events leading to SMA.

Amino Acid Sequence↗

PubMed2000

A multipurpose phantom for quality assurance of contrast-enhanced MR imaging of the breast.

A phantom consisting of four components was developed to simulate contrast-enhanced MR imaging of the breast. These components included the correlation between the signal intensity and the contrast medium concentration, the uniformity of signals within surface coils, artefacts due to opposed-phase imaging effects, spatial resolution and the acquisition of relevant signal-to-time curves. Repetitive measurements demonstrated an excellent reproduction of phantom imaging with a deviation in signal intensity of approximately 5 %. The presented phantom allows the optimization of examination protocols as well as the comparison of different examination techniques. Furthermore, it enables the routine quality monitoring of contrast-enhanced MR imaging of the breast.

Breast↗

PubMed2000

3D MR angiography of the entire aorta: modified application of the body-phased array coil for a single-shot technique.

OBJECTIVE: Evaluation of different contrast-enhanced MR angiography imaging protocols for visualization of the entire aorta in breath-hold technique. METHODS AND PATIENTS: Three different CE (0.15 mmol/kg) MRA protocols were evaluated by phantom and patient studies: (1) two separate MRA with conventional application of the body-phased array coil; (2) a single-shot MRA with modified application of the body-phased array coil; (3) a single-shot MRA with the body coil. Duplex sonography, CTA and DSA were used as standard of reference. RESULTS: In all examinations the entire aorta could be visualized. The best SNR was acquired with protocol (1). The SNR of protocol (2) was reduced if the sagittal body diameter of the patient was greater than 20 cm and decreased significantly with diameters over 30 cm. By the use of protocol (3) the SNR was notably poor. The quality scored for the visualization of the entire aorta was 97.5% (protocol 1); 92.5% (protocol 2); and 80.0% (protocol 3). CONCLUSION: In most cases the modified application of the body-phased array coil allows the imaging of the entire aorta as a single-shot 3D CE MRA in diagnostic quality.

Adolescent↗

PubMed2000

Enhanced green fluorescent protein fusion proteins of herpes simplex virus type 1 thymidine kinase and cytochrome P450 4B1: applications for prodrug-activating gene therapy.

To monitor therapeutic transgene expression, we developed fusion genes of enhanced green fluorescent protein (EGFP) with two different prodrug-activating enzyme genes: herpes simplex virus type 1 thymidine kinase (HSV-tk) and rabbit cytochrome P450 4B1 (cyp4b1). Expression of the resulting fusion proteins, TK-EGFP and 4B1-EGFP, rendered transduced human and rodent glioma cells sensitive to cytotoxic treatment with the corresponding prodrugs ganciclovir and 4-ipomeanol. Ganciclovir and 4-ipomeanol sensitivity was comparable with that achieved with the native HSV-TK and CYP4B1 proteins. As shown by fluorescence microscopy, TK-EGFP was expressed predominantly intranuclearly, whereas 4B1-EGFP was detectable in the cytoplasm, thereby displaying the orthotopic subcellular distribution of the corresponding native enzymes. The fluorescence intensity correlated well with the corresponding prodrug sensitivity, as shown by fluorescence-activated cell sorter analysis. EGFP expression was also used for the selection of stably HSV-tk-transduced cells by flow cytometric cell sorting. Resulting cell populations showed a homogeneity of fluorescence intensity similar to single-cell clones after antibiotic selection. In conclusion, tk-egfp and 4b1-egfp fusion genes are valuable tools for monitoring prodrug-activating gene therapy in living cells. EGFP fusion genes/proteins provide a simple and reproducible means for the detection, selection, and characterization of cells expressing enzyme genes for prodrug activation.

Animals↗

PubMed2000

[Stent artifacts in 3D MR angiography: experimental studies].

PURPOSE: The purpose of this phantom study was to evaluate the visualization of vascular stents by using contrast-enhanced (CE) 3D MR angiography (MRA). METHODS: The measurements were performed on a Magnetom Vision operating at 1.5 T with 25 mT/m gradients by using a head coil; a 3D FISP sequence (TR/TE/FA 4.6 ms/1.8 ms/30 degrees) was used. A phantom was designed with a length of 20 cm and consisted of a plastic cylinder filled with hydrogel. Tubes were used to install 7 different stents (Strecker, Boston Scientific; Cragg, Mintec; Wall, Schneider; Memotherm, Angiomed; St-Come, Trigon-MTS; Sinus, Optimed; Palmaz, Johnson & Johnson) with different metal components. The tubes were perfused with a solution of water and Gd-DTPA. Four radiologists evaluated the image quality. The measurements of the endoluminal stent diameters were compared with the findings obtained by digital subtraction angiography. The signal intensities were measured before (inflow), within (stent) and after (outflow) the different stent types. RESULTS: The endoluminal diameter of the Cragg stent and the strecker graft were easily detectable. The signal loss within the lumen of the Wall stent was approx. 10% in relation to the inflow and outflow measurements. The result was an only slightly reduced image quality. The other grafts (St-Come, Sinus, Palmaz, Memotherm) showed significant signal losses ranging from 65% to 96%. A correct diagnosis was not possible within these graft lumina. CONCLUSION: Contrast-enhanced MR angiography can be used to evaluate vascular stents. A prerequisite is the application of particular commercially available grafts.

Angiography, Digital Subtraction↗

PubMed2000

[Full-field digital mammography: a phantom study for detection of microcalcification].

OBJECTIVES: The study compares direct full-field digital mammography (FFDM) to the state-of-the-art conventional screen-film mammography (SFM) concerning the detectability of simulated microcalcifications. MATERIALS AND METHODS: The investigations were performed with a FFDM system (Senographe 2000D, GEMS) and a SFM system (Senographe DMR, GEMS, Fuji UM MA film with Fuji UM MAMMO FINE screen). An anthropomorphic breast phantom with superimposed microcalcifications (50-200 microns) was used to evaluate the detectability of microcalcifications with a confidence level ranging from 1 to 5. Contact mammograms and magnification spot views (m = 1.8) of the FFDM and SFM systems were compared. A receiver operating characteristic (ROC) analysis was performed by three well-experienced readers. RESULTS: The ROC analysis revealed a higher performance of the digital images compared to the conventional screen-film mammograms. The area under the ROC-curve (Az) in the digital contact mammograms was 0.68 versus 0.63 in the conventional technique. The results were not significantly different. In digital spot views, Az was 0.79 versus 0.70 in the conventional spot views. CONCLUSIONS: The results suggest that FFDM is at least equivalent or--as far as spot views are concerned--may be superior to conventional SFM in the detection of microcalcifications.

Breast Diseases↗