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Biomedical subjects

U Fischer

Publications and source records attributed to U Fischer.

At least 163 records · Page 9Linked to original sources

[MR angiography of the pelvic-leg blood vessels: current status and perspectives].

Currently 2D time-of-flight (TOF) MR angiography (MRA) is most commonly used for the evaluation of the extremities. The major limitation of all MRA techniques is their susceptibility to signal loss from intra-voxel phase dispersion. This leads to an overestimated grading of the stenosis. Further difficulties are motion artifacts and the limited spatial resolution. Therefore, MRA alone cannot be used routinely as a preoperative diagnostic procedure in patients with peripheral arterial disease. The postoperative examination of patients with vascular bypasses, however, seems to be a practical application of this technique. It is also possible to use MRA to image the lower limbs after percutaneous interventional angioplasty. The application of 2D-ECG-triggered sequences or the current fast technique of contrast-enhanced 3D-TOF MRA might play a role in combination with surface coils for future examinations of peripheral arterial disease.

Arterial Occlusive Diseases↗

[Asymptomatic aneurysm of the ileocolic artery].

Visceral aneurysms are rare and account for only 5% of all abdominal aneurysms. Most often they cause no symptoms and are therefore incidental findings. Doppler ultrasonography is the diagnostic method of choice. Therapeutic procedures can be performed either surgically of by interventional therapeutic techniques. This article presents a patient case with an ileocolic artery aneurysm.

Aged↗

Amphibian transcription factor IIIA proteins contain a sequence element functionally equivalent to the nuclear export signal of human immunodeficiency virus type 1 Rev.

The human immunodeficiency virus type 1 (HIV-1) Rev protein is required for nuclear export of late HIV-1 mRNAs. This function is dependent on the mutationally defined Rev activation domain, which also forms a potent nuclear export signal. Transcription factor IIIA (TFIIIA) binds to 5S rRNA transcripts and this interaction has been proposed to play a role in the efficient nuclear export of 5S rRNA in amphibian oocytes. Here it is reported that amphibian TFIIIA proteins contain a sequence element with homology to the Rev activation domain that effectively substitutes for this domain in inducing the nuclear export of late HIV-1 mRNAs. It is further demonstrated that this TFIIIA sequence element functions as a protein nuclear export signal in both human cells and frog oocytes. Thus, this shared protein motif may play an analogous role in mediating the nuclear export of both late HIV-1 RNAs and 5S rRNA transcripts.

Amino Acid Sequence↗

Identification of interleukin 1-induced apoptosis in rat islets using in situ specific labelling of fragmented DNA.

To study the ability of interleukin 1-beta (IL-1) to induce apoptosis in the endocrine pancreas, rat islets of Langerhans obtained from 14-day-old BB.1A rats were exposed to 25 U/ml IL-1 for 40 h. In order to prove the role of nitric oxide (NO) in this process islets were exposed either to 1 mmol/l N-nitro-L-arginine methylester (NAME) or to 25 mmol/l nicotinamide (NA) or to a combination of NA or NAME with IL-1. In dispersed cells oligonucleosomes, resulting from cleavage of nuclear DNA due to apoptosis, were identified by enzymatic labelling the free 3'-OH-DNA ends with fluorescein-dUTP and quantified by means of flow cytometry. After exposure to IL-1, the islets were characterized by elevated basal (in response to 2 mmol/l glucose) insulin release while glucose-stimulated (20 mmol/l glucose) insulin secretion was nearly completely abolished. In contrast, glucose-stimulated insulin secretion was well preserved in NAME-exposed islets, but was markedly inhibited after NA treatment. Accordingly, only the IL-1-induced inhibition of glucose-stimulated insulin secretion was significantly restored in the presence of NAME but was reinforced by NA. IL-1 exposure resulted in a significant increase in the percentage of apoptotic cells (untreated controls 3.8 +/- 0.5% IL-1 18.8 +/- 1.8%, P < 0.01). This effect was significantly reduced in the presence of NA and NAME. Nitrite production which was assayed as an equivalent of NO generation of islets was highest under the influence of IL-1 (16.48 +/- 1.40 versus 2.89 +/- 0.37 pmol/islet for control islets) which was correlated with the percentage of apoptotic cells. IL-1-stimulated nitrite production was reduced to 9.25 +/- 0.48 and 3.41 +/- 0.36 pmol/islet in the presence of NA or NAME, respectively. The results demonstrate the potency of IL-1 to induce apoptosis in rat islets. Since inhibition of NO production was always paralleled by a reduced ability of IL-1 to induce programmed cell death, this radical appears to be involved in this process. Remarkably, the near-complete prevention of NO generation as demonstrated under the influence of NAME was able to prevent the IL-1-induced deterioration of glucose-stimulated insulin secretion in parallel to the prevention of apoptosis-related appearance of DNA double-strand breaks. It is concluded that the elimination of damaged beta cells due to IL-1 exposure is partly achieved by induction of apoptosis.

Animals↗

Twelve amplified and expressed genes localized in a single domain in glioma.

Gene amplification has been associated both with tumor stage and progression in human gliomas. Several distinct amplified loci have been identified by comparative genomic hybridization and Southern blot analysis. It has been increasingly recognized that amplified domains comprise multiple genes. Here, we demonstrate amplification of up to 12 different genes from an amplified domain at 12q13-15 that has been found in approximately 15% of astrocytomas and glioblastomas. The amplified genes were GLI, WNT1, MDM2, SAS, CDK4 OS-4, GAS16, GAS27, GAS41, GAS56, GAS 64 and GAS89. In one glioblastoma all 12 amplified genes were also found to be expressed. These results strongly warrant the search for as yet unidentified genes in regions previously reported to be amplified.

Animals↗

Signal-mediated nuclear export pathways of proteins and RNAs.

Although it has been known for several years that most nuclear-encoded RNAs and some patients can be exported from the nucleus to the cytoplasm, the molecular mechanisms of these transport processes have been poorly understood. Recently, signals that can induce the rapid and active nuclear export of macromolecules have been identified in the HIV-1 Rev protein, the inhibitor of cAMP-dependent protein kinase (PKI) and the hnRNP A1 protein. Thus, nuclear export appears to be mechanistically similar to nuclear import that it requires specific signal-receptor systems.

Journal Article↗

Radical cystectomy with or without adjuvant polychemotherapy for non-organ-confined transitional cell carcinoma of the urinary bladder: prognostic impact of lymph node involvement.

OBJECTIVES: To analyze the effectiveness of adjuvant polychemotherapy after radical cystectomy for non-organ-confined transitional cell bladder cancer (Stages pT3b, pT4a, and/or pN1 or pN2). METHODS: Of 166 consecutive patients undergoing cystectomy at two institutions from 1987 to 1993, 80 received adjuvant polychemotherapy with methotrexate, vinblastine, and cisplatin plus doxorubicin (MVAC) or epirubicin (MVEC), whereas 86 had cystectomy only. The patients were evaluated for relapse-free survival and length of progression-free interval on the basis of follow-up data obtained in 1995 and 1996. RESULTS: Kaplan-Meier analysis revealed a significantly higher progression-free rate for patients after adjuvant chemotherapy (P = 0.0002, log-rank test). With and without adjuvant chemotherapy, prognosis declined in a stepwise manner, depending on the extent of lymph node involvement. Nevertheless, the superior prognosis of the chemotherapy group could be demonstrated at each lymph node stage. Of the 166 patients, 49 had initially entered a prospective trial comparing adjuvant with no adjuvant treatment. That study was discontinued in December 1990 after an interim analysis revealed a significant prognostic advantage in favor of the 26 patients randomized to receive chemotherapy compared with the 23 control patients. Current follow-up data continue to demonstrate a significant improvement in progression-free survival in favor of patients randomized to receive adjuvant chemotherapy (P = 0.0040). The follow-up period of patients living free of disease ranges from 58 to 96 months. CONCLUSIONS: Adjuvant chemotherapy with MVAC/MVEC leads to significant prolongation of relapse-free survival and improvement of the definitive cure rate after radical cystectomy for locally advanced transitional cell carcinoma of the urinary bladder.

Adult↗

[2-D-time-of-flight MR angiography of the peripheral blood vessels. Experimental and clinical studies on value of this method in arterial occlusive diseases].

PURPOSE: A retrospective study was performed in 70 patients with peripheral vascular disease who underwent MR angiography of the lower extremity. MATERIAL AND METHODS: MR angiography was performed with a 2-D-TOF sequence including a travelling presaturation to suppress the venous signal. Postprocessing images were obtained with the MIP algorithm. The MRA results were compared with conventional or digital angiography in all patients. RESULTS: Only 19 stenoses out of 31 which showed a degree of stenosis between 30 and 99% could be visualised by MR angiography. 9 stenoses were correctly classified by MRA. In 9 cases the degree of stenosis was overestimated, in one case it was underestimated. All 56 occlusions were correctly detected. 12 severe stenoses diagnosed with conventional angiography were graded as occlusions with MR angiography. CONCLUSIONS: MR angiography cannot be accepted in preoperative staging of patients with peripheral vascular disease. The postoperative examination seems to be a practical noninvasive alternative.

Algorithms↗

[Ductal carcinoma in situ in dynamic MR-mammography at 1.5 T].

PURPOSE: To define the value of contrast-enhanced MR mammography in ductal carcinoma in situ (DCIS). MATERIAL AND METHODS: In a group of 35 patients with DCIS, the results of MR imaging were compared to histopathology and immunohistochemistry in a retrospective study. RESULTS: In 35 patients with DCIS, a signal enhancement was found in 25 cases (72%). In 15 of these cases, the signal time curve was typical for malignancy. The other 10 patients had non-specific signal curves. Six of 35 patients (11%) had no enhancement within the tumour region. Four of 35 patients (11%) had bilateral diffuse signal increase, and regions of DCIS could not be identified clearly. Three DCIS were visualised exclusively by MR mammography. The configuration of signal enhancement was sharp (32%), unsharp (48%) or dendritic (20%). DCIS of the comedo type showed a significantly higher enhancement than the non-comedo type. A significant correlation between the grade of vascularisation in immunohistochemistry and signal enhancement in MR mammography could not be demonstrated. CONCLUSION: Dynamic MR mammography does not reliably visualise DCIS.

Adult↗

[MRI-controlled intervention in suspected lesions of the breast].

PURPOSE: To evaluate two different systems for magnetic resonance (MR) imaging-guided breast interventions. MATERIALS AND METHODS: 41 patients with 41 lesions detected exclusively with contrast-enhanced MR imaging underwent 68 interventional procedures (27 needle biopsies and 41 preoperative wire localisations) with two different systems. An add-on device for surface coils was used in 39 cases, and a dedicated single breast biopsy coil was used in 29. For needle biopsies, material was aspirated with nonmagnetic 19.5 gauge needles. For preoperative localisations, nonmagnetic wires were used. RESULTS: Surgical excision verified the cytological findings in 23 of the 27 cases sampled for biopsy. Cytological diagnosis was impossible in three cases. One technical failure occurred with the biopsy coil. Open biopsy performed after MR imaging-guided localisation successfully removed 38 of the 41 lesions. One missed carcinoma was found at repeat localisation and removed. Two technical failures occurred with the biopsy coil. In these cases, the lesions were close to the chest wall. CONCLUSIONS: Both systems are suitable for MR-guided fine-needle biopsy and preoperative localisation of breast lesions seen exclusively on MR images.

Biopsy, Needle↗

Isolation of genes amplified in human cancers by microdissection mediated cDNA capture.

It has been increasingly recognized that homogeneously staining regions (hsr) in human cancers may be complex structures composed of large amplified DNA domains containing multiple genes. It is therefore important to devise strategies for the rapid isolation of cDNAs expressed from these structures. Using a procedure we term microdissection mediated cDNA capture, we recovered hsr specific cDNAs from two different human tumors. The glioblastoma cell line TX3868 and the human sarcoma cell line OsA-CL carry hsrs containing amplified sequences from chromosome 12q13-15. We recovered 17 hsr specific cDNAs following microdissection of these hsrs which had been previously hybridized in situ with linkered cDNA. Northern blot analysis with these cDNAs revealed hybridization to distinct transcripts in OsA-CL RNA and TX3868 RNA. None of the OsA-CL cDNA clones showed cross hybridization with the TX3868 cDNAs suggesting that despite their coincident band localization on 12q, the OsA-CL and TX3868 amplification units do not completely overlap. These results significantly increase the number of amplified genes assigned to the 12q13-15 amplicon illustrating both the complexity of hsrs derived from this region and the utility of microdissection mediated cDNA capture to gain rapid access to cDNAs transcribed from amplified genes.

Base Sequence↗

Stereotaxic add-on device for MR-guided biopsy of breast lesions.

Breast biopsy and lesion localization were performed with gadolinium-enhanced magnetic resonance (MR) imaging guidance, with use of a stereotaxic biopsy system consisting of a flexible circular surface coil with an acrylic cylinder as an add-on guidance device. Twenty-five procedures (23 localizations, two core biopsies) were performed in lesions depicted at diagnostic MR imaging, without technical failure. The guidance system permitted easy, precise, and flexible biopsy and localization of all breast lesions.

Biopsy, Needle↗

Dual-phase helical CT of the liver: effects of bolus tracking and different volumes of contrast material.

PURPOSE: To evaluate the effects of tracking and volume of contrast material on dual-phase helical computed tomography (CT) of the liver. MATERIALS AND METHODS: CT was performed in 120 consecutive patients. Either 100 mL (groups 1 and 2) or 120 mL (groups 3 and 4) of contrast material was injected at a rate of 4 mL/sec. In groups 1 and 3, the scanning delay was fixed, whereas in groups 2 and 4, scanning delays were determined individually by means of a semiautomatic bolus tracking device. The arterial phase began when splenic enhancement was greater than 10 HU and ended when hepatic enhancement was greater than 20 HU, which characterized the start of the portal venous phase. RESULTS: The mean duration of the arterial phase was 11.6 (100 mL) and 12.2 seconds (120 mL). The arterial phase of the liver within the defined limits was sufficiently timed in only 16 (54%) patients in group 1, 25 (83%) in group 2, and 20 (67%) in groups 3, whereas it was significantly (P < .05) better in 28 (93%) patients in group 4. A significantly (P < .05) higher mean parenchymal enhancement in the portal venous phase (63.6 HU +/- 8.5) was obtained in group 4. CONCLUSION: Bolus tracking of a volume of 120 mL provided the most accurate results in dual-phase liver CT.

Adult↗

Increased urea synthesis in insulin-dependent diabetic dogs maintained normoglycemic: effect of portal insulin administration and food protein content.

In IDDM, the gluconeogenic turnover of amino acids is increased even if glycemia is well controlled and may be restored to normal by means of prehepatic insulin substitution. Therefore, the present study was designed 1) to investigate the influence of route of insulin administration (portal versus peripheral) on the urea production rate, which is considered to measure amino acid catabolism, and 2) to elucidate the impact of different food-protein intake. Paired studies were conducted in chronic insulin-dependent diabetic dogs maintained normoglycemic. Diabetic animals and nondiabetic controls were fed either a high-protein diet (46% of energy intake provided by proteins; study 1) or a low-protein carbohydrate-supplemented diet (20% of energy intake provided by protein; study 2) for 2 days, and flux rates of glucose and urea were measured using isotope dilution techniques. In both studies, the diabetic animals were maintained normoglycemic by glucose-controlled insulin infusion delivered either systemically or portally. In study 1 versus study 2, the animals showed lower alpha-amino nitrogen levels and concentrations of gluconeogenic amino acids, predominantly alanine. There were no significant differences in plasma glucose and glucose turnover between the experimental groups on either systemic or portal insulin infusion versus controls; however, peripheral insulin levels were higher for diabetic animals maintained with systemic versus portal insulin delivery (P < 0.05). No significant differences in glucagon, lactate, pyruvate, nonesterified fatty acids, or beta-hydroxybutyrate were observed. Urea production was significantly higher in study 1 compared with study 2: 7.48 +/- 0.83 vs. 5.97 +/- 0.59 micromol / kg / min (normal dogs); 12.97 +/- 1.86 vs. 5.54 +/- 0.60 micromol / kg / min (diabetic dogs on portal insulin); 16.11 +/- 2.59 vs. 6.82 +/- 0.70 micromol / kg / min (diabetic dogs on systemic insulin infusion); P < 0.05 for all. The diabetic dogs maintained normoglycemic with systemic insulin infusions had significantly higher rates of urea synthesis than those with portal insulin infusion (P < 0.05). It is concluded that in IDDM, even if normoglycemia is managed, there is significantly increased amino acid catabolism with posthepatic systemic insulin treatment. This increased catabolic rate is more pronounced during high-protein nourishment.

Animals↗

Rapid HPLC assay for verapamil and its metabolites: use for application to in vitro studies.

An improved method using isocratic reversed phase HPLC is presented for the extraction and rapid determination of verapamil and its main metabolites in microsomal preparations and cell culture media. Possibilities for using the method to estimate cytochrome P450 enzymes in microsomal test systems and hepatocyte cultures are described. The studies show that primary hepatocyte cultures are suitable for studying the metabolism and interactions of pharmaceuticals in vitro and could be superior to microsomal systems in many cases.

Biotransformation↗

[MR-mammography: current status and perspectives].

Dynamic MR imaging of the breast is viewed as an examination technique which is supplementary to mammography and sonography and which can provide important additional diagnostic information. Proven indications for MR mammography include examinations of patients who have undergone lumpectomy and patients with prosthetic breast implants. The method also appears to be useful to differentiate between postoperative scarring and carcinoma as well as to exclude a multicentric breast carcinoma prior to lumpectomy. The sensitivity of MR mammography, however, is limited in cases of DCIS. Hypervascular benign lesions can be difficult to distinguish from malignant lesions.

Breast↗