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Biomedical subjects

U Fischer

Publications and source records attributed to U Fischer.

At least 109 records · Page 6Linked to original sources

[The radial scar in contrast media-enhanced MR mammography].

INTRODUCTION: In patients with the mammographic findings of a radial scar, contrast enhanced (CE) MR mammography was evaluated in a retrospective study. MATERIAL AND METHODS: In 24 women with radial opacities and black star configurations, CE MR mammography was performed. Examinations were done on a 1.5 T system using bilateral superficial coil (2D technique, T1-weighted FLASH-sequence, TR 336 ms, TE 5 ms, FA 90 degrees). Findings in mammography and MR mammography were compared with the histological results. RESULTS: 15 radial scars (including 4 with additional ADH) and 9 carcinomas (6 in coexistence with a radial scar) presenting with a diameter of 3 mm to 13 mm were evaluated. There was no evidence of malignancy in MRI in 12 of 15 radial scars. In MR mammography 6 of the carcinomas fulfilled the criteria for malignant tumors. There were 3 borderline cases (scored 3 points) corresponding histologically to 1 radial scar, and to 2 carcinomas. Within the results found in MRI there were 2 false positives and 1 false negative. CONCLUSION: CE MR mammography is superior to other imaging modalities in the differentiation between radial scars and carcinomas. However, lesions suggestive of radial scars have to be removed surgically.

Adult↗

[Full-field digital mammography: dose-dependent detectability of breast lesions and microcalcinosis].

OBJECTIVES: The study compares contrast-detail and microcalcification detectability of a full-field digital mammography (FFDM) to a state-of-the-art conventional screen-film mammography (SFM) by using different doses in the digital system. MATERIALS AND METHODS: The investigations were performed with an FFDM (Senographe 2000 D, GEMS) and an SFM system (Senographe DMR, GEMS) using a contrast-detail mammography phantom (CDMAM) and an anthropomorphic breast phantom with superimposed microcalcifications. The digital detector was exposed with standard dose of SFM and with a dose reduction of up to 75%. Contrast-detail curves and correct observation ratio (COR) were performed for the CDMAM phantom. ROC analysis with a confidence level ranging from 1 to 5 was done with the results of the anthropomorphic phantom. RESULTS: Digital mammography with the same dose revealed at least an equivalent or even higher detectability rate than conventional mammography, COR could be increased at about 10-25%. The ROC analysis yielded better results for the FFDM system. The same lesion detectability in digital mammography as in the conventional method was reached at a dose reduction of about 25%, concerning spot views even at higher reduction. Dose reduction in the anthropomorphic phantom resulted in a linear loss of detectability. The same detectability as in conventional mammography was reached, however, by a dose reduction of about 50%. CONCLUSION: The results suggest that FFDM is at least equivalent to or--as far as spot views are concerned--superior to conventional SFM concerning the detectability of simulated lesions. Thus, a potential of dose reduction is suggested.

Breast Diseases↗

Identity testing in cervical carcinoma in case of suspected mix-up.

The histopathologic diagnosis is the cornerstone of modern oncology. But mix-ups of specimens can occur at any stage. The resection of a 1.2 cm polypoid cervical mass in a 25-year-old woman showed a poorly differentiated adenocarcinoma prospectively staged as T1b1 (International Federation of Gynecology and Obstetrics IB1). Even after complete embedding and serial sectioning of the whole cervix of the hysterectomy specimen after radical hysterectomy, only adenocarcinoma in situ, but no invasive tumor, was seen. To exclude a mix-up of the specimens, identity testing of the paraffin-embedded material was performed by microsatellite analysis. For both materials, we established identical results after testing the microsatellite loci HumTH01, HumVWA, HumFGA, HumACTBP2, HumF13B, and HumD8S1132. The resulting probability of identity came to 99.9999%, excluding a mix-up of the specimens. Archival paraffin-embedded specimens can be used to establish identity and can prevent the wrong patient from having major surgery.

Adenocarcinoma↗

Extracellular cyanobacterial substances inhibit microbial growth.

Cyanobacteria are able to produce extracellular substances with different biological activities and behaviors. The marine cyanobacteria Anabaena sp. strain Hi 26 and Oscillatoria subtilissima strain Bo 62 cause significant color changes in their growth media, while viscosity of the medium is influenced by Rivularia sp. strain Bo 85 and Oscillatoria limnetica strain Flo 1. Sterile-filtered media, pregrown with the organisms mentioned above, were used to study the influence of changes in media bioactivity induced by "excreted substances" on the growth and/or morphological development of five related filamentous cyanobacterial species and on selected heterotrophic microorganisms. Cell lysis, empty sheaths, different lengths of filaments, or even single cells and a decrease in chlorophyll a and protein content were the characteristic changes obtained by such a "cyanobacterial assay." The use of a "precultured" medium, as demonstrated in an "agar diffusion assay," affects in varying degrees the growth of gram-positive and gram-negative heterotrophic bacteria, as well as of the yeast Saccharomyces cerevisiae.

Anabaena↗

Structure and characterization of Ectothiorhodospira vacuolata cytochrome b(558), a prokaryotic homologue of cytochrome b(5).

A soluble cytochrome b(558) from the purple phototropic bacterium Ectothiorhodospira vacuolata was completely sequenced by a combination of automated Edman degradation and mass spectrometry. The protein, with a measured mass of 10,094.7 Da, contains 90 residues and binds a single protoheme. Unexpectedly, the sequence shows homology to eukaryotic cytochromes b(5). As no prokaryotic homologue had been reported so far, we developed a protocol for the expression, purification, and crystallization of recombinant cytochrome b(558). The structure was solved by molecular replacement to a resolution of 1.65 A. It shows that cytochrome b(558) is indeed the first bacterial cytochrome b(5) to be characterized and differs from its eukaryotic counterparts by the presence of a disulfide bridge and a four-residue insertion in front of the sixth ligand (histidine). Eukaryotes contain a variety of b(5) homologues, including soluble and membrane-bound multifunctional proteins as well as multidomain enzymes such as sulfite oxidase, fatty-acid desaturase, nitrate reductase, and lactate dehydrogenase. A search of the Mycobacterium tuberculosis genome showed that a previously unidentified gene encodes a fatty-acid desaturase with an N-terminal b(5) domain. Thus, it may provide another example of a bacterial b(5) homologue.

Amino Acid Sequence↗

Rev-mediated nuclear export of RNA is dominant over nuclear retention and is coupled to the Ran-GTPase cycle.

The human immunodeficiency virus type-1 Rev protein induces the nuclear export of intron-containing viral mRNAs that harbor its binding site, the Rev response element (RRE). A leucine-rich region of Rev, the activation domain, is essential for function and has been shown to be a nuclear export signal (NES). Although Rev exports viral RNAs that resemble cellular mRNAs, competition studies performed using microinjected Xenopus laevis oocytes have previously indicated that Rev utilizes a non-mRNA export pathway. Here, we show that Rev is able to induce the export of both spliceable and non-spliceable RRE-containing pre-mRNAs and that this activity is not dependent on the location of the RRE within the RNA. Importantly, even RNA molecules of different classes, such as U3 snoRNA and U6 snRNA, which are retained in the nucleus by non-pre-mRNA mechanisms, are exported to the cytoplasm in response to Rev. Consistent with the notion that Rev-mediated export of RRE-containing RNA is mechanistically distinct from the export of processed cellular mRNA, a chimeric Rev protein in which its NES is replaced by the NES of hnRNP A1 does not induce the export of a Rev-responsive mRNA. Finally, we demonstrate that Rev/RRE-activated RNA export is, like other nuclear export pathways, linked to the Ran-GTPase cycle.

Animals↗

Using fasting plasma glucose concentrations to screen for gestational diabetes mellitus: prospective population based study.

OBJECTIVE: To evaluate whether measuring fasting plasma glucose concentration is an easier screening procedure for gestational diabetes mellitus than the 1 hour 50 g glucose challenge test. DESIGN: Prospective population based study. SETTING: Outpatient clinic in a university hospital. PARTICIPANTS: 520 pregnant women (328 (63%) white, 99 (19%) Asian, 31 (6%) African, 62 (12%) others) with mean age 28.4 (SD 0.2; range 17-45) years. All underwent a glucose challenge test between the 24th and 28th gestational week, followed by a diagnostic 3 hour 100 g oral glucose tolerance test within one week. This was done irrespective of the result of the challenge test. MAIN OUTCOME MEASURE: Receiver operating curves were used to determine the best cut off values for screening with fasting plasma glucose concentrations. RESULTS: Fasting plasma glucose concentration at a threshold value of 4.8 mmol/l and the glucose challenge test with a threshold value of 7.8 mmol/l yielded sensitivities of 81% and 59% respectively and specificities of 76% and 91% respectively. Measuring fasting plasma glucose concentration as a screening procedure required a diagnostic test in 30%, compared with 14% when the challenge test was used. CONCLUSIONS: Measuring fasting plasma glucose concentrations using a cut off value of >/=4. 8 mmol/l is an easier screening procedure for gestational diabetes than the 50 g glucose challenge test and allows 70% of women to avoid the challenge test.

Adolescent↗

Monoclonal antibody specific to a subclass of polyproline-Arg motif provides evidence for the presence of an snRNA-free spliceosomal Sm protein complex in vivo: implications for molecular interactions involving proline-rich sequences of Sm B/B' proteins.

The human spliceosomal Sm B/B' proteins are essential for the biogenesis of the snRNP particles. B/B' proteins contain several clusters of the PPPPGM/IR sequence, which occurs within the C-terminus of Sm B/B'. This sequence is very similar to the PPPPPGHR sequence of the cytoplasmic tail of the CD2 receptor and closely resembles the class II of SH3 ligands, suggesting a similarly important role. We report that a monoclonal antibody (3E10) against the PPPPPGHR sequence recognizes spliceosomal Sm B/B' proteins. Proteins that are specifically immunoprecipitated by 3E10 include Sm B, B', D1, D2, D3, E, F, and G. However, unlike Y12 and other anti-Sm immunoprecipitates, 3E10 immunoprecipitates appear to lack the U1 snRNP-specific proteins A and C and U snRNAs. These findings indicate that 3E10 recognizes a subset of Sm protein core and suggest the presence of snRNA-free Sm protein complex(es) in vivo. We propose that the epitope binding for 3E10 may become unaccessible upon interactions of Sm proteins and their subsequent incorporation into the core particles. The Sm proline-rich sequences may have an important role in mediating protein-protein interactions necessary for the proper snRNP core assembly or function, or both. To our knowledge, 3E10 is the first well characterized mAb specific for a subclass of polyproline-arg motif recognizing Sm B/B' and CD2 proteins. 3E10 antibody can be used to further characterize the nature of protein components in the snRNA-free Sm subcore protein complex(es) that are formed during the snRNP core assembly steps.

Amino Acid Sequence↗

The Sm core domain mediates targeting of U1 snRNP to subnuclear compartments involved in transcription and splicing.

In the mammalian cell nucleus pre-mRNA splicing factors such as U snRNPs are concentrated in distinct subnuclear compartments named perichromatin fibrils (PFs), interchromatin granules (IGs), interchromatin granule-associated zones (IG-associated zones), and coiled bodies (CBs). The structural requirement for the localization of U snRNPs to these domains was investigated by microinjection of digoxygenin-labeled in vitro-reconstituted U1 snRNPs and mutants thereof and subsequent analysis by immunoelectron microscopy. Wild-type U1 snRNP was targeted, after injection into the cytoplasm, to the nucleus and localized in PFs, IGs, IG-associated zones, and CBs. Thus, microinjected U1 snRNP particles exhibited a subnuclear localization similar to that previously observed for endogenous U1 snRNPs. Specific U snRNP proteins were shown not to be essential for subnuclear targeting since U1 snRNP mutants that did not bind to 70K, A, or C peptides were distributed in the cell nucleus in a pattern indistinguishable from that of wild-type U1 snRNP. Moreover, the Sm core domain, common to all spliceosomal U snRNPs, was shown to be sufficient for appropriate subnuclear distribution. Thus, these observations indicate that the Sm core domain, previously shown to be essential for nuclear import of spliceosomal U1 snRNPs, is also important for mediating the targeting to distinct nuclear subcompartments.

Cell Compartmentation↗

[Preoperative MR mammography in breast carcinoma. Effect on operative treatment from the surgical viewpoint].

INTRODUCTION: In a prospective study the diagnostic validity of magnetic resonance mammography (MRM) as well as its impact on the choice of the operative procedure in the treatment of breast cancer was examined. In 125 patients who were suspected of having breast cancer by clinical examination, ultrasound, and X-ray mammography, additional bilateral MRM was performed. Of special interest was the diagnostic potential of MRM with regard to multifocal, multicentric and contralateral lesions. METHODS: After a complete resection all lesions diagnosed by the various conventional methods were examined patho-histologically. In 112 patients, complete data were available to calculate the sensitivity and the specificity of each method as well as to correlate its results with the pathohistological findings. RESULTS: In 91 cases, a breast carcinoma was diagnosed by conventional methods, with a sensitivity/specificity of 73%/67% for clinical examination, of 58%/86% for ultrasound, and of 89%/20% for X-ray mammography. In this preselected series of patients with a prevalence of 81.25% the diagnosis established by the various methods was confirmed by MRM with sensitivity of 96.7% and specificity of 19%. Forty-six additional suspicious lesions were found only by MRM, of which 28 were malignant (25 multifocal or multicentric and 3 contralateral carcinomas), and 18 benign. The rate of false-positive MRM results was 18%. Due to the MRM findings, the therapeutic procedure was changed from breast preservation to mastectomy in 14.3%. CONCLUSION: Not only for the differential diagnosis of discrepant findings between X-ray mammography and ultrasound, but especially for the diagnosis of multifocal or multicentric lesions, MRM seems to be the method of choice. Consequently, MRM plays an important role in planning the operative procedure in breast cancer patients, especially in the context of breast preservation. To ensure optimal use of this new diagnostic tool high technical standards, proper expertise on the part of the examining radiologist, and effective cooperation among the involved disciplines (radiology, pathology, surgery) must be guaranteed.

Adult↗

MRI of the breast in patients with metastatic disease of unknown primary.

The objective of this study was to assess the value of contrast-enhanced dynamic breast imaging in patients with carcinoma of unknown primary (CUP). Fourteen patients presenting with metastatic disease compatible with breast cancer (axillary lymph node metastasis: n = 6; supraclavicular lymph node metastasis: n = 1; bone metastasis: n = 3; liver metastasis: n = 3; lung metastasis: n = 1), who had no evidence of tumor in X-ray mammograms and ultrasound, underwent bilateral dynamic breast MR imaging. Suspicious lesions were localized preoperatively using a stereotactic device for MR-guided localization procedures. Magnetic resonance imaging revealed suspicious lesions in 9 of 14 patients. Histopathology revealed invasive carcinoma of the breast in 6 of these patients. Two enhancing lesions were fibroadenomas; one proved to be sclerosing adenosis. In 5 patients MR imaging showed no abnormality. Follow-ups performed up to 1 year after initial treatment revealed no breast cancers in these 5 patients. In patients with metastatic disease of unknown primary, MRI of the breast depicts the primary in a considerable number of cases with normal conventional evaluation.

Adult↗

Unusual chondrosarcoma of the larynx: CT findings.

A case of a large low-grade mixed clear-cell and conventional chondrosarcoma of the larynx is reported involving the paraglottic space, the cricoid and thyroid cartilage and characterized by an unusual long clinical course over 22 years, although multiple recurrences occurred without developing metastases. Computed tomography suggests diagnosis by detecting calcifications and adequately demonstrates the extension of the tumor. Innersurface and surface-rendering images document the airway stenosis in all directions. The unusual feature of this case consists in the peculiar histopathological differentiation of the observed chondrosarcoma showing a large clear-cell component.

Chondrosarcoma↗

Penetration of ciprofloxacin, norfloxacin and ofloxacin into the aqueous humor using different topical application modes.

BACKGROUND: A prospective study was undertaken to determine the transcorneal penetration of three topically applied fluoroquinolones into aqueous humor. METHODS: Cataract patients (n = 224) preoperatively received topically applied gyrase inhibitors (0.3% ciprofloxacin, 0.3% norfloxacin, 0.3% ofloxacin) in two different application modes. In application mode I, patients received on the day before operation 3 x 1 eye drop at 2-h intervals, and on the day of operation 3 drops at 1-h intervals. In application mode II, patients received 9 drops at 15-min intervals on the day of operation only. Just before cataract surgery 50-100 ml aqueous humor was aspirated and stored at -80 degrees C. The HPLC method was used for measuring the concentration. RESULTS: The highest concentrations of all tested antibiotics were measured after the mode of application in which one drop was given every 15 min between 06:00 and 08:00 hours before operation. In this mode, ciprofloxacin achieved a mean aqueous level of 379.8 +/- 327.8 mg/l (range 33-1388 mg/l), norfloxacin 182.1 +/- 118.1 mg/l (range 38-480 mg/l) and ofloxacin 563.9 +/- 372.1 mg/l (range 64-1455 mg/l). These mean concentration are all above the MIC90 of gram-negative bacteria like Proteus mirabilis and Escherichia coli. In some cases the concentrations of ciprofloxacin and ofloxacin, but never norfloxacin, reached therapeutic values above the MIC90 of Staphylococcus aureus and Staphylococcus epidermidis. CONCLUSIONS: The mean concentration value of 0.3% ciprofloxacin and of 0.3% ofloxacin in the aqueous humor reached the MIC90 values of the frequently occurring gram-positive and gram-negative bacteria. Of the currently available topical fluoroquinolones, ofloxacin achieved the highest aqueous humor concentration. Considering the higher antimicrobial activity of ciprofloxacin, both ciprofloxacin and ofloxacin may be useful ophthalmic agents in antibacterial management, but they are not efficient against Streptococcus pneumoniae and Pseudomonas aeruginosa.

Administration, Topical↗

Glucagon-like peptide-1 has no insulin-like effects in insulin-dependent diabetic dogs maintained normoglycemic and normoinsulinemic.

A pharmacological concentration of glucagon-like peptide-1 (GLP-1) in the insulin-deficient state clearly decreases the blood glucose level. Therefore, this study was designed to evaluate a putatively relevant effect of the gastrointestinal peptide as an adjuvant to insulin replacement therapy. GLP-1 (GLP-1(7-36) amide 10 pmol x kg(-1) x min(-1)) was infused intravenously over 8 hours in nine fasting, C-peptide-negative diabetic dogs. The animals were under normoglycemic control by glucose-controlled insulin infusion (GCII) during the night before and during GLP-1 administration. During the paired control tests, the animals received saline infusion instead of GLP-1. In addition to the insulin infusion rates required to maintain normoglycemia, hormones, metabolites, and the turnover rates for glucose (6-3H-glucose), alanine (U-14C-alanine), and urea (15N2-urea) were measured during the final 2 hours of GLP-1 administration. Circulating plasma GLP-1 levels increased from 3+/-1 to 17+/-7 pmol/L. There was no significant difference in the insulin infusion rate between the experimental and control groups (0.43+/-0.05 v. 0.40+/-0.05 mU x kg(-1) x h(-1), average over the entire interval). Glycemia was maintained at a practically identical level (4.9+/-0.3 v. 4.8+/-0.4 mmol/L). Also, the concentration of plasma insulin-which was not hyperinsulinemic--and pancreatic glucagon remained unaltered. We found no appreciable effect of GLP-1 on glucose production and metabolic clearance, alanine turnover and the formation of glucose from alanine (1.8+/-0.2 v. 1.4+/-0.2 micromol x kg(-1) x min(-1), or the urea production rate as a measure of overall amino acid catabolism (4.1+/-0.4 v. 4.1+/-0.4 micromol x kg(-1) x min(-1)). Thus, no conclusive adjuvant effect of GLP-1 was ascertained in insulin-treated diabetic dogs under normoglycemic control.

Animals↗

Body nitrosation potential measured by a novel 15N breath test.

Oxygenated nitrogen species, for example, the protonated form of nitrous acid (H2ONO+), dinitrogentrioxide (N2O3), dinitrogentetroxide (N2O4), or peroxynitrite (ONOO-), can react with amines to form molecular nitrogen. These reactions can occur spontaneously with primary aliphatic amines or via cytochrome P450 catalysed reactions with secondary amines. In principle measurements of the excretion of the molecular nitrogen generated by these reactions could be used as an index of the levels of oxygenated nitrogen compounds acting as nitrosating agents. To test this idea, [15N2]urea (3 mmol) was administered orally to five patients infected with Helicobacter pylori (as diagnosed by the [13C]urea breath test) and to four healthy volunteers. All participants ingested 3-mmol sodium nitrate as a precursor for NA 5 min before the ingestion of the nitrogen tracer. During the test the participants breathed 100% oxygen to increase the sensitivity of detection of endogenous molecular nitrogen. After the administration of [15N2]urea, the patients with H. pylori showed significantly increased 15N enrichments of exhaled N2, expressed as delta value (per 1000), compared with healthy volunteers (patients: 3.5 +/- 0.9 vs. volunteers: 1.3 +/- 0.4; p < .05). We speculate that the endogenous production of molecular nitrogen is a protective process controlling the body NO and nitrite levels. The 15N breath technique allows the noninvasive estimation of the body nitrosation and could indicate the health risk, possibly the oxidative stress status, caused by highly reactive oxygenated nitrogen species and carbenium ion intermediates.

Adult↗

Septic endarteritis and fatal iliac wall rupture after endovascular stenting of the common iliac artery.

A 52-year-old female with arterial occlusive disease underwent an uneventful percutaneous transluminal angioplasty and placement of a vascular metallic stent in the left common iliac artery. Ten days later she presented with clinical symptoms of septic endarteritis. Shortly after re-admittance, an emergency laparotomy had to be performed because of an acute retroperitoneal bleeding. Rupture of the common iliac artery directly overlaying the penetrating stent was found but control of haemorrhage was of no avail. In this report of a case, septic endarteritis following placement of a vascular metallic stent preceded fatal rupture of the common iliac artery. This up to now unknown constellation requires surgical intervention without undue delay.

Angioplasty, Balloon↗

Biodegradation of a high molecular weight aliphatic ether--indications of an unusual biodegradation pathway.

An aliphatic ether (1-phytanyl-1-octadecanyl-ether) of high molecular weight was used as a sole carbon source in degradation experiments with different aerobic bacteria. The enriched culture B5, obtained from fuel contaminated soils, was able to degrade the substance for more than 90%. A culture of Rhodococcus ruber was similarly effective. Detailed investigation of the metabolites allowed us to characterize an unusual degradation pathway via a mid-chain oxidation mechanism ('internal oxidative pathway'). Obviously, formation of intermediate alkenes mainly at the unbranched side chain was a prerequisite for bacterial degradation of the added substrate. Degradation proceeded - in spite of the usually preferred terminal oxidation - via oxidation of the internal double bond and was followed by an ester cleavage. In turn, a series of alcohols was formed which were subsequently oxidized to the respective carboxylic acids and were further metabolized via the normal beta-oxidation pathway.

Alcohols↗

Expression of functional alpha7 nicotinic acetylcholine receptor during mammalian muscle development and denervation.

We have studied, on the transcriptional, protein and functional level, the expression of alpha7 nicotinic acetylcholine receptors (nAChR) in the course of rat muscle development, denervation and renervation. At foetal day 13, alpha7 nAChR expression was observed in somites and developing muscles of the back, but not yet in migrating myoblasts. Two days later, concomitant with myoblast aggregation, the alpha7 isoform began to be expressed in isolated myoblasts, with the highest level of expression in the frontal zone of the migrating wave. On foetal day 18, a time when the myoblasts in the upper hindleg have fused, alpha7 nAChR expression was most prominent in the outer layer of muscle tissue. The highest level of expression was observed in the first postnatal week, when practically all muscle cells stained positively for alpha7 protein. During the following weeks, alpha7 nAChR expression slowly decreased and practically disappeared in adult hindleg muscle. Following chronic denervation of adult Soleus muscle fibres, expression of alpha7 nAChR returned within 2-4 weeks. Electrophysiological measurements showed that the alpha7 nAChR of chronically denervated soleus muscle fibres were functional and, in particular, that they could be activated by choline. The presence of the alpha7 nAChR in developing and denervated muscle suggests a role for this nicotinic receptor in neuronal pathfinding and/or endplate stabilization.

Animals↗