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Biomedical subjects

U Hahn

Publications and source records attributed to U Hahn.

At least 109 records · Page 6Linked to original sources
PubMed1998

Gd-enhanced 3D phase-contrast MR angiography and dynamic perfusion imaging in the diagnosis of renal artery stenosis.

The objective of this study was to investigate the role of contrast enhancement using a three-dimensional (3D) phase-contrast (PC) magnetic resonance (MR) sequence (3D PC-MRA) and to assess the value of a dynamic MR perfusion study of the kidneys to determine the hemodynamic relevance of unilateral renal artery stenosis (RAS). Seventeen patients with unilateral RAS were examined on a standard 1.0 T imaging system using a phase shift and magnitude sensitive 3D PC sequence (TR=160 ms, TE=9 ms, venc. 30 cm/s). Following the initial pre-contrast 3D PC-MRA a dynamic first pass perfusion study was performed using a Turbo-FLASH 2D sequence (TR=4.5 ms, TE=2.2 ms, TI=400 ms) after bolus injection of 0.15 mmol gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)/kg body weight. The 3D PC-MRA was then repeated during infusion of 0.15 mmol Gd-DTPA/kg body weight. Evaluation by three independent readers was based on maximum intensity projection images. Source images were rendered on request. Signal intensity (SI) over time curves of the renal cortex were obtained from the dynamic perfusion study and analyzed for maximum signal enhancement as well as temporal relationship to the aortic SI curve. Results from 3D PC-MRA revealed a sensitivity (pre-/post-contrast) of 100%/89%, specificity of 76%/63%, positive predictive value of 80%/69 %, negative predictive value of 90%/78%, and accuracy of 85%/75% (p=0.07). Interobserver agreement was kappa=0.61/kappa=0.47 (pre/post Gd-DTPA), respectively. Increased signal-to-noise was present in all segments of the renal arteries post contrast (p=0.0003). This came along with image degradation due to aliasing and elevated SI of venous flow that partially obscured the renal arteries. Dynamic SI curves showed a significantly decreased maximum SI in RAS (p=0.01-0.001). A temporal delay of cortical signal intensity enhancement could not be confirmed in this setting. Gd-enhanced 3D PC-MRA did not yield a superior diagnostic value in the diagnosis of RAS compared to pre-contrast measurements. Dynamic perfusion imaging of the kidneys, in combination with 3D PC-MRA, can contribute additional information in suspected unilateral RAS.

Aged↗
PubMed1998

Increased risk of catheter colonization and catheter-related infections in severe immunocompromized patients with multiple myeloma undergoing high-dose glucocorticoid treatment.

Catheter-related infections (CRI) are an important problem in medicine because of major consequences for treatment, prolongation of hospitalization and increasing therapy costs. Malignancies, immunodeficiency, severe burns and malnutrition compromise host defense. Studies to quantify the increased risk of CRI in immunocompromised patients are required. We analyzed the influence of immunoglobulin deficiency and high-dose glucocorticoid treatment in patients with multiple myeloma with regard to catheter colonization and CRI. In patients with multiple myeloma, central venous catheters (CVC) were significantly more frequently colonized (> 15 CFU) as compared to patients with other malignancies undergoing chemotherapy. We found a tendency towards a higher CRI rate in the myeloma patient group. Interestingly, despite of the significantly higher incidence of catheter colonization and a tendency towards higher CRI rates in severely immunocompromised patients, the incidence of signs of local (redness of the entry site) and systemic (fever) host reactions is reduced in myeloma patients. To decrease the CRI rate in myeloma patients during chemotherapy which includes high-dose glucocorticoids, we use antibacterial (silver-coated) catheters.

Adolescent↗
PubMed1998

Why discourse structures in medical reports matter for the validity of automatically generated text knowledge bases.

The automatic analysis of medical full-texts currently suffers from neglecting text coherence phenomena such as reference relations between discourse units. This has unwarranted effects on the description adequacy of medical knowledge bases automatically generated from texts. The resulting representation bias can be characterized in terms of artificially fragmented, incomplete and invalid knowledge structures. We discuss three types of textual phenomena (pronominal and nominal anaphora, as well as textual ellipsis) and outline basic methodologies how to deal with them.

Artificial Intelligence↗
PubMed1998

Part-whole reasoning in medical ontologies revisited--introducing SEP triplets into classification-based description logics.

The development of powerful and comprehensive medical ontologies that support formal reasoning on a large scale is one of the key requirements for clinical computing in the next millennium. Taxonomic medical knowledge, a major portion of these ontologies, is mainly characterized by generalization and part-whole relations between concepts. While reasoning in generalization hierarchies is quite well understood, no fully conclusive mechanism as yet exists for part-whole reasoning. The approach we take emulates part-whole reasoning via classification-based reasoning using SEP triplets, a special data structure for encoding part-whole relations that is fully embedded in the formal framework of standard description logics.

Artificial Intelligence↗
PubMed1997

Conformation of thermally denatured RNase T1 with intact disulfide bonds: a study by small-angle X-ray scattering.

Small-angle X-ray scattering of RNase T1 with intact disulfide bonds was measured at 20 degrees and 60 degrees C in order to get insight into the structural changes of the protein caused by thermal denaturation. The radius of gyration increases from R(G)= 1.43 nm to R(G) = 2.21 nm. The conformations of the molecules at 60 degrees C are similar to those of ring-shaped random walk chains. However, the molecules are more compact than one would expect under theta conditions due to attractive interactions between the chain segments. The volume needed for free rotation of the thermally unfolded protein molecules about any axis in solution is five times greater than in the native state whereas the hydrodynamic effective volume is increasing only two times.

Disulfides↗
PubMed1997

[Ambulatory therapy of multiple myeloma with vincristine, adriamycin and dexamethasone].

BACKGROUND AND OBJECTIVE: If multiple myeloma (MM) progresses in patients after chemotherapy with alkylating agents, the combination of vincristine, adriamycin and dexamethasone (VAD) can achieve a response in 40-70% of cases. Because of its low toxicity for haematopoetic stem-cells this form of chemotherapy is often undertaken before high-dose blood stem-cell transplantation. It was the objective of this study to examine effectiveness and complications of ambulant VAD treatment. PATIENTS AND METHODS: Within four years VAD chemotherapy was given to 62 ambulant MM patients, administered by microprocessor-regulated pumps via intravenously polyurethane catheters with a safety valve. Response to treatment, treatment-associated complications and infections were documented prospectively and analysed. RESULTS: VAD treatment achieved tumour reduction of more than 25% in 50 of 62 patients. This treatment had to be discontinued in two of 192 pump-infusions because of irreversible catheter occlusion. Eight patients were hospitalised because of infections and two for noninfectious complications. Severe infectious complications (> or = WHO grade III) occurred in 4% of treatment cycles. CONCLUSION: VAD chemotherapy can be performed with a low rate of infection in ambulant patients despite the need for prolonged intravenously infusion of the drugs. But to avoid complications by intravenously catheters, random prospective tests should first be done with oral alkylating agents.

Adult↗
PubMed1997

Ribonuclease T1 has different dimensions in the thermally and chemically denatured states: a dynamic light scattering study.

Ribonuclease T1 can be unfolded and refolded without forming noticeable amounts of aggregates allowing to characterise the dimensions of a protein in different denatured states in terms of the Stokes radius RS. Upon thermal unfolding RS increases from 1.74 nm at 20 degrees C to 2.14 nm at 60 degrees C. By contrast, RS = 2.40 nm was obtained at 5.3 M guanidinium chloride (GuHCl) and 20 degrees C. Heating from 20 degrees C to 70 degrees C in the presence of 5.3 M GuHCl led to a 5% decrease in RS.

Escherichia coli↗
PubMed1997

Measurements of emittance and absolute spectral flux of the PETRA undulator at DESY Hamburg.

The first synchrotron radiation beamline using a 4 m-long undulator at the 12 GeV storage ring PETRA delivers hard X-ray photons usable up to 300 keV. The photon intensity is measured on an absolute scale in the energy range between 16 and 60 keV and compared with calculated intensities. The experimental set-up described is also used to measure the horizontal and vertical emittance of the source.

Journal Article↗
PubMed1997

Tandem high-dose therapy with ifosfamide, epirubicin, carboplatin and peripheral blood stem cell support is an effective adjuvant treatment for high-risk primary breast cancer.

We evaluated the therapeutic efficacy and toxicity of a tandem high-dose therapy with peripheral blood stem cell (PBSC) support in 40 patients with high-risk, primary breast cancer (stage II-III) and involvement of ten or more positive axillary lymph nodes. Their median age was 44 years (range 23-56). Two cycles of cytotoxic chemotherapy with ifosfamide (10000 mg/m2) and epirubicin (100 mg/m2) were administered. Granulocyte colony-stimulating factor (G-CSF) was given to hasten neutrophil reconstitution and to mobilise PBSC during marrow recovery. Leukaphereses were performed following the first and/or second cycle. Tandem high-dose therapy consisted of two cycles with ifosfamide (15 or 12 g/m2) and epirubicin (150 mg/m2), while carboplatin (900 mg/m2) was added for the last 24 patients included. Using an immunocytochemical method, two of 11 patients had cytokeratin-positive tumour cells in three leukapheresis products that were collected following the first G-CSF-supported cycle with ifosfamide and epirubicin, whereas only two harvests obtained following the second cycle in 26 patients contained cytokeratin-positive tumour cells. The number of CD34+ cells/kg re-infused following both high-dose cycles was similar (4.20 +/- 0.29 x 10(6), first cycle and 5.25 +/- 0.63 x 10(6), second cycle), and no notable difference was noted in the speed of haematological reconstitution. An absolute neutrophil count (ANC) of 0.5 x 10(9)/1 was reached after a median time of 13 days, while an unsupported platelet count of 20.0 x 10(9)/1 was achieved after a median time of 8 (first cycle) and 9 (second cycle) days post-transplantation. Patients autografted with more than 7.5 x 10(6) CD34+ cells/kg had platelet counts above 20 x 10(9)/1 within less than 10 days. 6 patients relapsed between 7 and 11 months (median 8 months) post-transplantation. 37 patients are alive and in remission with a median follow-up time of 11 months (range 1-38). This translates into a probability of disease-free survival (DFS) of 77% (95% CI 32-95%) at 38 months. The probability of overall survival is 85%, since 3 patients with local relapse achieved a second complete remission following surgery and involved-field radiotherapy. In conclusion, a sequential high-dose therapy including ifosfamide, epirubicin, carboplatin and PBSC support is well tolerated and effective in patients with high-risk primary breast cancer. Involved-field irradiation should be performed post-transplantation to reduce the risk of local relapse.

Adult↗
PubMed1997

Exclusion of bioactive contaminations in Streptococcus pyogenes erythrogenic toxin A preparations by recombinant expression in Escherichia coli.

The streptococcal erythrogenic exotoxin A (SPEA) belongs to the family of bacterial superantigens and has been implicated in the pathogenesis of a toxic shock-like syndrome and scarlet fever. Concerning its biological activity, mainly T-cell-stimulatory properties, conflicting data exist. In this study, we show that most of the SPEA preparations used so far contain biologically active contaminations. Natural SPEA from the culture supernatant of Streptococcus pyogenes NY-5 and recombinant SPEA purified from the culture filtrate of S. sanguis are strongly contaminated with DNases. We show that natural SPEA induces more tumor necrosis factor alpha (TNF-alpha) than recombinant SPEA, but we also show that DNases are able to induce TNF-alpha. In commercial SPEA preparations, we identified a highly active protease, which was shown not to be SPEB. To exclude these contaminations, we overexpressed SPEA cloned in the effective high-level expression vector pIN-III-ompA2 in Escherichia coli. The expressed SPEA shows the same amino acid composition as natural SPEA, whereas functional studies reported so far were carried out with toxins containing an incorrect amino terminus. We describe the rapid purification of lipopolysaccharide-, DNase-, and protease-free SPEA in two steps from the host's periplasm and its structural characterization by circular dichroism. Our results represent for the first time the production in E. coli of recombinant SPEA with the authentic N-terminal sequence and a proven superantigenic activity. Collectively, our results indicate that immunological studies of superantigens require highly purified substances free of biologically active contaminations.

Animals↗
PubMed1997

Reverse action of ribonuclease T1 in frozen aqueous systems.

We have studied ribonuclease T1 (EC 3.1-27.3)-catalysed synthesis of guanylyl-(3'-->5')cytidine in frozen aqueous reaction mixtures at -10 degrees C and in solution at 0 degree C in order to investigate whether ribonuclease-catalysed synthetic reactions can take advantage of the yield-increasing effect of freezing as was reported for protease-catalysed peptide synthesis. Under frozen state conditions, substantially increased yields of GpC were obtained compared to the reactions in solution. From the fact that no irreversible hydrolysis of the 2'3'-cyclic donor was observed it can be concluded that transesterification of the newly formed phosphodiester bond is the most important yield-limiting factor in ribonuclease T1-catalysed dinucleoside phosphate synthesis.

Dinucleoside Phosphates↗
PubMed1997

Overproduction of Sac7d and Sac7e reveals only Sac7e to be a DNA-binding protein with ribonuclease activity from the extremophilic archaeon Sulfolobus acidocaldarius.

Genomic DNA from Sulfolobus acidocaldarius was screened using a degenerate oligodeoxyribonucleotide, derived from the sequence of 16 N-terminal amino acids from SaRD protein. SaRD protein was previously isolated in our laboratory and identified as a protein from S. acidocaldarius exhibiting ribonuclease activity as well as DNA-binding properties. On the basis of Southern hybridization analysis two genes from S. acidocaldarius have been cloned, sequenced and overproduced in Escherichia coli. The deduced amino acid sequences revealed that one gene encodes Sac7d and the other one Sac7e; two small, previously described basic proteins from S. acidocaldarius, and furthermore the N-termini of Sac7e and SaRD are identical. Northern blot analysis demonstrated that the genes are transcribed separately. After expression of sac7d and sac7e genes in E. coli it was shown that only recombinant Sac7e protein exhibits RNase activity and is catalytically indistinguishable from SaRD protein. Western blot analysis using a polyclonal antiserum raised against purified SaRD protein further confirmed that Sac7e and SaRD are identical proteins endowed with RNase activity and DNA-binding properties. A new RNA cleavage mechanism has to be postulated for Sac7e since, in contrast to common RNases (e.g. RNase A and T1), no histidines are present in the amino acid sequence. Differences between the very closely related 7 kDa proteins from two Sulfolobus strains converting DNA-binding proteins into RNases are pointed out and discussed, whereas substitutions of Glu by Gln (S. solfataricus) or by Lys (S. acidocaldarius) seem to be crucial.

Amino Acid Sequence↗
PubMed1997

Ribonuclease T1 is active when both catalytic histidines are replaced by aspartate.

The enzymatic activity of many ribonucleases (RNases) depends on two histidines, as in RNase A, or one histidine and/or glutamate, as in microbial RNases belonging to the T1 family. In RNase T1, substitution of either one or both of the two histidines at positions 40 and 92 by a variety of other amino acids reduces the activity more than 100-fold. However, the double variant His40-->Asp/His92-->Asp retains a significant residual enzymatic activity towards RNA and guanylyl-3',5'-cytidine, indicating that a pair of substituted side chains in these positions, both with acid functionality, can confer enzymatic activity. It was shown that the substitution of histidine with glutamate in the variant His40-->Glu yields an enzyme with drastically reduced activity and leads to inactivation in the His92-->Glu, His40-->Glu/His92-->Glu variants. For the variants where histidine is substituted with aspartate we found measurable activity from 1% (His40-->Asp) to 6% (His40-->Glu/His92-->Asp) towards RNA.

Aspartic Acid↗
PubMed1997

Text structures in medical text processing: empirical evidence and a text understanding prototype.

We consider the role of textual structures in medical texts. In particular, we examine the impact the lacking recognition of text phenomena has on the validity of medical knowledge bases fed by a natural language understanding front-end. First, we review the results from an empirical study on a sample of medical texts considering, in various forms of local coherence phenomena (anaphora and textual ellipses). We then discuss the representation bias emerging in the text knowledge base that is likely to occur when these phenomena are not dealt with--mainly the emergence of referentially incoherent and invalid representations. We then turn to a medical text understanding system designed to account for local text coherence.

Hospital Information Systems↗
PubMed1996

Early recurrence or persistence of autoimmune diseases after unmanipulated autologous stem cell transplantation.

Autologous stem cell transplantation with or without in vitro lymphocyte depletion has been suggested as a new treatment option for severe autoimmune diseases. We describe five patients with autoimmune diseases (CREST syndrome, myasthenia gravis and Hashimoto's thyroiditis, systemic lupus erythematosus, atopic dermatitis, and rheumatoid arthritis) who underwent autologous bone marrow (n = 1) or peripheral blood progenitor cell (n = 4) transplantation with unmanipulated grafts as treatment for the autoimmune disease in one case or as treatment for a malignant disorder with a concomitant autoimmune disorder in four cases. In all patients serological and clinical signs of the autoimmune disease recurred early or persisted. These observations should be regarded as a cautionary note concerning the efficacy of high-dose therapy followed by transplantation of unmanipulated autologous stem cells for treatment of severe autoimmune diseases.

Adult↗
PubMed1996

The role of a trans-proline in the folding mechanism of ribonuclease T1.

Protein folding is often retarded by the cis reversible trans isomerizations of prolyl peptide bonds both in vitro and in vivo. An important role for the folding mechanism is well established for the prolyl peptide bonds that are cis in the native protein, but not for those that are trans. Here we investigated the role of trans-Pro73 for the folding of ribonuclease T1 (which additionally contains two cis-prolines) by comparing the wild-type protein with the Pro73-->Val variant. The Pro-->Val substitution led to a destabilization of the folded protein by 8.5 kJ/mol, which is explained by the strong, 25-fold increase in the rate of unfolding. In contrast, the rates and amplitudes of the fast and slow refolding reactions were virtually unchanged. trans-Proline residues remain largely trans after unfolding, and therefore their contributions to the observed folding kinetics should indeed be insignificant for proteins which also contain one or more cis prolines. The cis-proline residues dominate the kinetics of refolding, because almost all slow-folding molecules contain the respective incorrect (trans) isomers, and because trans-->cis isomerizations are slower than cis-->trans isomerizations. The inability to detect contributions from a trans-proline to the kinetics of folding does not imply that this proline is non-essential for folding in the sense that its cis reversible trans isomerization is energetically uncoupled from conformational folding.

Enzyme Stability↗
PubMed1996

A general ribonuclease assay using methylene blue.

Ribonuclease (RNase) activity has been assayed by monitoring the shift in the absorbance maximum of methylene blue upon intercalation into high-molecular-weight RNA. After preincubation of yeast RNA with methylene blue, the initial rate of hydrolysis can be followed spectrophotometrically at a wavelength of 688 nm. This allows enzyme kinetic studies of RNases with their probable native substrate, RNA, in place of the artificial ones, such as dinucleoside phosphates or cyclic monophosphates, currently used.

Kinetics↗