Biomedical subjects

U Hahn

Publications and source records attributed to U Hahn.

At least 19 recordsLinked to original sources

PubMed2001

Molecular characterization of the 56-kDa CYP153 from Acinetobacter sp. EB104.

CYP153 a cytochrome P450 from Acinetobacter sp. EB104 catalyzes the hydroxylation of unsubstituted n-alkanes. We have decided to use the CYP153 system as a model for mechanistic studies on regioselective n-alkane oxidation and the interaction of hydrophobic substrates with soluble enzymes. Here the molecular cloning of the CYP153 gene is reported. Single specific primer PCR was applied to yield the whole gene sequence via chromosomal walks. CYP153 consists of 497 amino acids (M(r) = 56 kDa) and thus represents an unusually long bacterial P450, containing all P450 typical structural elements. It constitutes the new P450 family CYP153. The prolonged N-terminus of about 90 amino acids does not contain a so far known membrane-anchoring sequence but a 28-amino acid long amphipathic helix. The relevance of the remarkably long N-terminus and of other sequence motives like the hydrophobic F-G loop is discussed with respect to substrate binding and recognition.

Acinetobacter↗

PubMed2001

Novel biomarkers of the metabolism of caffeic acid derivatives in vivo.

The purpose of this study was to investigate biomarkers of the bioavailability and metabolism of hydroxycinnamate derivatives through the determination of the pharmacokinetics of their urinary elimination and identification of the metabolites excreted. Coffee was used as a rich source of caffeic acid derivatives and human supplementation was undertaken. The results show a highly significant increase in the excretion of ferulic, isoferulic, dihydroferulic acid (3-(4-hydroxy-3-methoxyphenyl)-propionic acid), and vanillic acid postsupplementation relative to the levels presupplementation. Thus, ferulic, isoferulic, and dihydroferulic acids are specific biomarkers for the bioavailability and metabolism of dietary caffeic acid esters. Isoferulic acid is a unique biomarker as it is not a dietary component, however, dihydroferulic acid may well derive from other flavonoids with a structurally related B-ring. 3-Hydroxyhippuric acid has also been identified as an indicator for bioavailability and metabolism of phenolic compounds, and shows a highly significant excretion increase postsupplementation. The results reveal isoferulic acid (and possibly dihydroferulic acid) as novel markers of caffeoyl quinic acid metabolism.

Adult↗

PubMed2001

Epicatechin and its in vivo metabolite, 3'-O-methyl epicatechin, protect human fibroblasts from oxidative-stress-induced cell death involving caspase-3 activation.

There is considerable current interest in the cytoprotective effects of natural antioxidants against oxidative stress. In particular, epicatechin, a major member of the flavanol family of polyphenols with powerful antioxidant properties in vitro, has been investigated to determine its ability to attenuate oxidative-stress-induced cell damage and to understand the mechanism of its protective action. We have induced oxidative stress in cultured human fibroblasts using hydrogen peroxide and examined the cellular responses in the form of mitochondrial function, cell-membrane damage, annexin-V binding and caspase-3 activation. Since one of the major metabolites of epicatechin in vivo is 3'-O-methyl epicatechin, we have compared its protective effects with that of epicatechin. The results provide the first evidence that 3'-O-methyl epicatechin inhibits cell death induced by hydrogen peroxide and that the mechanism involves suppression of caspase-3 activity as a marker for apoptosis. Furthermore, the protection elicited by 3'-O-methyl epicatechin is not significantly different from that of epicatechin, suggesting that hydrogen-donating antioxidant activity is not the primary mechanism of protection.

Antioxidants↗

PubMed2001

Subacute myocardial infarction: assessment by STIR T2-weighted MR imaging in comparison to regional function.

PURPOSE: Increased T2 signal intensity (SI) can be regularly observed in myocardial infarction. However, there are controversial reports about the relationship of elevated T2 SI to myocardial viability and some authors propose that high T2 SI serves as a sign of irreversible myocardial injury. This study investigates increased T2 SI compared to myocardial function in patients with reperfused subacute myocardial infarction. Preserved function was used as criterion for viability. METHODS: Ten healthy volunteers and 17 patients with myocardial infarction and patent infarct related coronary artery were examined on a 1.5 T Magnetom Vision system (Siemens). For T2-weighted MR imaging a breath-hold STIR sequence with dark-blood preparation was used. Cine FLASH 2D imaging was applied to assess myocardial function. Signal-to-noise (S/N) in STIR T2 images was measured in normal and infarcted regions and subsequently identified by two independent observers. Based on a 20 segment model of the left ventricle findings were compared to regional myocardial function. RESULTS: Elevated STIR T2 SI was found in all 17 patients and observed in 27% (204/754) of segments. S/N of normal myocardium was 5.1 +/- 0.7 in volunteers and 4.9 +/- 0.8 in patients (P = NS). Infarcted myocardium presented with significantly increased S/N 12.8 +/- 1.9 (P < 0.0001). Significant transmural elevation of T2 SI was noted in 32% of segments with preserved systolic function. CONCLUSION: Increased STIR T2 SI can be observed transmurally in post-ischemic myocardial regions with preserved function. It therefore cannot be used as an exclusive marker for the non-viable region.

Aged↗

PubMed2001

[Diagnosis of intra-articular fracture of the head of the tibia. A prospective comparative study].

Complete visualization of the joint surface is essential for correct assessment of tibial head fractures. Conventional tomography, computed tomography (CT), and magnetic resonance imaging (MRI) are compared in this prospective study. We examined 27 patients (19 suffering from B fractures and 8 from C fractures) from 1 January 1995 to 11 November 1998. Conventional tomography underestimated the fractures in 3 of the 19 cases of B fractures. Computed tomography underestimated two of these cases. MRI could not exactly depict the essential structures in three of the eight cases of C fractures because of edema and effusions. MRI identified complete cruciate ligament rupture in 6 of the 27 cases (18%) and 10 meniscal ruptures in 9 cases (33%: 6 medial meniscus, 4 lateral meniscus). Complete ruptures of the lateral collateral ligament were detected in five cases and medial collateral ligament ruptures in two cases. According to this, 63% of the patients suffered from relevant accompanying soft tissue injuries. The rate of soft tissue injuries increased up to 92% including the partial collateral ligament ruptures. Local hospital conditions permitting, X-ray-loaded conventional tomography should no longer be used in tibial head fractures. X-ray-free MRI is most efficient in cases of B fractures, which can in most cases be treated with a minimum of invasive techniques. Computed tomography is to be used in cases of C fractures that are regularly managed by open surgery accompanied by direct visualization of the inside of the knee joint.

Adult↗

PubMed2001

Outpatient treatment of multiple myeloma with a combination of vincristine, Adriamycin and dexamethasone.

Patients with relapsed multiple myeloma (MM) have been shown to respond to a combination therapy consisting of vincristine, Adriamycin (doxorubicin) and high-dose dexamethasone (VAD). Because of the low hematological toxicity of the VAD regimen, this combination is frequently chosen for tumor reduction prior to high-dose therapy and blood stem cell transplantation. This study was designed to examine the efficacy and complications of outpatient VAD treatment. Over a period of 6 years, 103 outpatients with MM were treated with VAD chemotherapy administered by microprocessor-controlled infusion pumps via intravenous polyurethane catheters equipped with a safety valve. Response to treatment, treatment-associated complications and infections were documented and analyzed. In 85 of the 103 patients, tumor reduction by more than 25% was found. In 8 patients an occlusion occurred as a result of kinking of the central venous catheter in the subcutaneous segment. In two treatment cycles the infusions had to be stopped because of irreversible catheter occlusion. Twenty patients were hospitalized because of complications, which were infectious in 12 and noninfectious in 8. Severe infectious complications (> or =WHO grade III) occurred in 5.6% of the treatment cycles. Thus, continuous infusion of VAD over 96 h can be performed on an outpatient basis with a low complication rate.

Adult↗

PubMed2001

New strategies in platelet inhibition in noncoronary interventions.

Thrombembolic complications frequently occur during and after endovascular procedures because of associated arterial injury and thrombotic characteristics of implanted devices such as stents. New strategies in platelet aggregation inhibition are now available blocking the final and common pathway of platelet aggregation, the glycoprotein IIb/IIIa receptor. This treatment modality seems to be more effective for prophylaxis and prevention of thrombembolic complications than standard antiplatelet therapy. Most of the data provided for glycoprotein IIb/IIIa receptor blockade are derived from studies of coronary interventions. This report reviews the pharmacodynamic differences of classic and new drugs for platelet inhibition and the basic considerations for antiplatelet therapy in noncoronary interventions.

Arteries↗

PubMed2001

[Endovascular therapy of renal artery stenosis: technical results with the Palmaz-Corinthian stent].

OBJECTIVE: To evaluate the technical performance and delivery characteristics of the Palmaz-Corinthian stent for endovascular therapy of atherosclerotic renovascular disease. METHODS: 61 patients underwent implantation of 76 Palmaz-Corinthian (PC) stents in 72 arteries. 50 original PC and 26 PC stents with the modified IQ-design were employed. The indications comprised primary stenting of ostial (n = 49) or truncal (n = 1) stenosis or occlusion (n = 3), and selective stenting following complicated (dissection, n = 4) or unsuccessful (n = 8) angioplasty. The remaining stents were placed in patients with recurrent stenosis (n = 5) or acute aortic dissection (n = 2) involving the renal artery. Mean severity and length of stenosis were 81.3% and 9.8 mm, respectively. 39 lesions were rated eccentric or calcified. Data on technical success, complication rate, delivery characteristics and ease of placement compared to standard renal stents were retrieved from a prospective multicenter registry. RESULTS: Stent delivery was successful in all patients, major complications were not reported. Stent placement was suboptimal in 7 of 72 cases: 4 stents were located too distally in the renal artery, necessitating proximal coaxial overstenting in 2 cases. The distal part of the stenosis was incompletely covered and the orifice of a segmental branch inappropriately overstented in one case each. One stent was dislodged from the balloon, resulting in stent protrusion in the aortic lumen. Significant residual stenosis after stenting was not observed. Overall stent deliverability, trackability and potential repositioning inside the stenosis were rated positive, radio-opacity was rated superior for the IQ design. CONCLUSION: Technical performance and delivery characteristics of the Palmaz-Corinthian stent have been significantly improved compared to the Palmaz design, allowing mostly correct placement in renal artery stenoses with a low complication rate.

Angiography, Digital Subtraction↗

PubMed2001

Fluorescence correlation spectroscopy as a new method for the investigation of aptamer/target interactions.

Fluorescence correlation spectroscopy is an attractive tool for monitoring molecular interactions in solution. We report here a new and highly sensitive method for studying the interaction of aptamers with their targets using this technique. In vitro selection technology is a combinatorial method for the generation of nucleic acid receptors (aptamers) that are capable of binding to various target molecules. Using the in vitro selection approach we isolated RNAs which bind to the antibiotic moenomycin with high affinity. The formation of RNA-moenomycin complexes was studied by fluorescence correlation spectroscopy with a tetramethylrhodamine-labeled derivative of moenomycin.

Combinatorial Chemistry Techniques↗

PubMed2001

RNase-stable RNA: conformational parameters of the nucleic acid backbone for binding to RNase T1.

An RNA sequence showing high stability with respect to digestion by ribonuclease T1 (RNase T1) was isolated by in vitro selection from an RNA library. Although ribonuclease T1 cleaves single-stranded RNA specifically after guanosine residues, secondary structure calculations predict several guanosines in single-stranded areas. Two of these guanosines are part of a GGCA-tetraloop, a recurring structure element in the secondary structure predictions. Molecular dynamics simulations of the conformation space of the nucleotides involved in this tetraloop show on the one hand that the nucleic acid backbone of the guanosines cannot realise the conformation required for cleavage by RNase T1. On the other hand, it could be shown that an RNA molecule not forced into a tetraloop occupies this conformation several times in the course of the simulation. The simulations confirm the GGCA-tetraloop as an RNase-stable secondary structure element. Our results show that, besides the known prerequisite of a single-stranded RNA, RNase T1 has additional demands on the substrate conformation.

Base Sequence↗

PubMed2001

A new device for percutaneous suture-mediated closure of arterial puncture sites using exteriorized needles: initial experience.

PURPOSE: To assess the feasibility and initial clinical results of Closer (Perclose, Redwood City, California), a new device for percutaneous suture-mediated closure of arterial puncture sites. METHODS: Vascular interventions were performed using 6 and 7 French sheaths in 22 consecutive patients. All patients underwent suture-mediated percutaneous closure with the new device. Patients were followed by physical examination the day after the procedure. RESULTS: Immediate hemostasis was achieved in 20/22 patients (91%). In 3 out of 5 antegrade closures, only one suture was captured. In two cases, this was managed by reinsertion of a second device. In another patient, hemostasis was not achieved by the device due to knot entrapment. No major complications were observed. The overall rate of minor complications was 9% (2/22) due to hematomas without the need for blood transfusions. CONCLUSION: Percutaneous suture with this new device is an acceptably safe and effective method to achieve immediate hemostasis of the arterial access site after interventional procedures with minimized manipulation of the puncture track.

Adult↗

PubMed2000

Epicatechin and catechin are O-methylated and glucuronidated in the small intestine.

There is considerable interest in the bioavailability of polyphenols and their bioactivity in vivo. We have studied the absorption and metabolism of catechin and epicatechin in the small intestine and the comparative transfer across the jejunum and ileum. Perfusion of isolated jejunum with the flavanols resulted in glucuronidation ( approximately 45%), O-methylation: 3'-O-Methyl- and 4'-O-methyl- ( approximately 30%), and O-methyl-glucuronidation ( approximately 20% of total flavanols identified) during transfer across the enterocytes to the serosal side. This demonstrates the activity of catechol-O-methyl transferases in the metabolism of flavanols and suggests that these metabolites and conjugates are likely to enter the portal vein. In contrast, in the case of the ileum, the majority of the flavanols appeared on the serosal side unmetabolised and the total percentage of flavanols transferred was higher than that in the jejunum ( approximately fivefold).

Animals↗

PubMed2000

Resveratrol is absorbed in the small intestine as resveratrol glucuronide.

We have studied the absorption and metabolism of resveratrol in the jejunum in an isolated rat small intestine model. Only small amounts of resveratrol were absorbed across the enterocytes of the jejunum and ileum unmetabolised. The major compound detected on the serosal side was the glucuronide conjugate of resveratrol (96.5% +/- 4.6 of the amount absorbed) indicating the susceptibility of resveratrol to glucuronidation during transfer across the rat jejunum. The presence of the glucuronide was confirmed using HPLC-PDA and nanoES-MS/MS techniques. These findings suggest that resveratrol is most likely to be in the form of a glucuronide conjugate after crossing the small intestine and entering the blood circulation. This will have important implications for the biological functions of resveratrol in vivo.

Animals↗

PubMed2000

Nano-electrospray mass spectrometry with a modified commercial IonSpray source

Electrospray mass spectrometry is a standard tool for the investigation of biological samples. Due to the high flowrates of the standard sources, large sample amounts are required and it is almost impossible to spray physiological solutions due to their aqueous medium. The introduction of microelectrospray sources has made it possible to decrease the sample amounts needed and enabled the use of buffered solutions. In this work, a nanoES-like source based on a modification of an existing IonSpray source is introduced. In contrast to other nanoES sources available, the modification presented allows a fast change between the nanoES and the normal IonSpray modes. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗

PubMed2000

German inflection: single route or dual route?

The German plural system has recently become a focal point for conflicting theories of language, both linguistic and cognitive. Marcus et al. (1995) highlight the German plural as support for the dual-route account of inflectional morphology first proposed by Pinker and colleagues (Pinker & Prince, 1988). On the dual-route account, inflectional morphology is universally subserved by a symbolic rule route which deals with regular inflection and an associative memory component which deals with irregular inflection. This contrasts with single-route connectionist systems. We seek to counter supposed evidence for the dual-route account through large-scale simulations as well as through experimental data. We argue that, in its current form, the dual-route account is incapable of generating experimental data provided by Marcus et al. (1995) as support. Finally, we provide direct quantitative comparisons between single-route and dual-route models of German plural inflection and find single-route performance superior on these tests.

Humans↗

PubMed2000

[Polytopic manifestations of paragangliomas. Diagnosis, differential diagnosis and indications for therapy].

Paragangliomas of the glomus caroticum are relatively rare, but highly vascularized neoplasmas, which develop from chemoreceptors. They can be develop at any age, but most often in the third or fourth decade of life. Paragangliomas grow very slowly and are most always of benign origin. There is a familial predisposition, and an autosomal-dominant transmission is presumed. They are commonly located in the jugular region; in rare cases a polytopic manifestation is found. We describe the case of a 47-year-old male patient who was referred to our department because of a progressive swelling of the neck on both sides. Contrast-enhanced computed tomography had displayed soft tissue tumors in the jugular regions. We performed an operative exploration, which showed a highly vascularized tumor. Histopathologic analysis revealed the diagnosis of a paraganglioma. An angiography of the neck and thoracic region, furthermore, revealed an additional paraganglioma in the anterior mediastinum. Using a surgical approach via lateral cervicotomies and thoracotomy the paragangliomas were extirpated. Our case report demonstrates the rare polytopic manifestation of paragangliomas. This perivascular neoplasms have to be removed before haemodynamic complications develop. The extent of this tumors is clearly illustrated by use of an angiography. Because of the familial predisposition, clinical and radiological examinations of relatives are mandatory.

Carotid Body↗

PubMed2000

Conventional high resolution versus fast T(2)-weighted MR imaging of the heart: assessment of reperfusion induced myocardial injury in an animal model.

Cardiac image quality in terms of spatial resolution and signal contrast was assessed for conventional and newly developed T(2)-weighted fast spin-echo imaging with high k-space segmentation. The capability in revealing regional myocardial edema and cellular damage was examined by a porcine model using histopathologic correlation. Twelve porcine hearts were excised from slaughtered animals and instantly perfused with 1000 mL cold cardioplegic solution. After 4 h of cold ischemia the hearts were reperfused for one hour using a "Langendorff" perfusion model followed by MR imaging at 1.5 Tesla. Three additional pig hearts served as controls and were studied by MR directly after harvesting. Histopathological analysis of regional tissue changes was performed macro- and microscopically. Short axis T(2)-weighted (3000/45 and 90) high quality fast spin-echo (FSE) images were recorded without cardiac action and signal intensity was correlated with histology. These images also served as gold standard for evaluation of newly developed faster sequences allowing measuring times shorter than 20 s. Fast T(2)-weighted imaging comprised single-slice fast spin echo (moderate echo train length of 23 echoes, FSE(m)), and multi-slice single-shot half-Fourier fast spin-echo (71 echoes, FSE(HASTE)) sequences, supplemented by versions with inversion recovery preparation (FSE(m)IR and FSE(HASTE)IR). Systolic function after reperfusion was restored in 10 porcine hearts. Tissue alterations included myocardial edema and contraction band necrosis which was found to be most severe in myocardium with maximum T(2) SI. Especially FSE(m) and FSE(m)IR sequences allowed differentiation of all categories of tissue damage on a high level of significance. In contrast, single-shot FSE(HASTE) and FSE(HASTE)IR sequences did not provide sufficient image quality to discriminate moderate and severe myocardial damage (p > 0.05). Different degrees of myocardial injury after ischemia and reperfusion can be staged by MR imaging, especially using conventional high resolution T(2)-weighted FSE sequences. The animal study indicates that fast T(2)-weighted FSE(m) and FSE(m)IR sequences lead to superior image quality and diagnostic accuracy compared to FSE(HASTE) and FSE(HASTE)IR imaging.

Analysis of Variance↗

PubMed2000

Morpheme-based, cross-lingual indexing for medical document retrieval.

The increasing availability of machine-readable medical documents is not really matched with the sophistication of currently used retrieval facilities to deal with a variety of critical natural language phenomena. Still most popular are string-matching methods which encounter problems for the medical sublanguage, in particular, concerning the wide-spread use of complex word forms such as noun compounds. We introduce a methodology for the segmentation of complex compounds into medically motivated morphemes. Given the sublanguage patterns in our data these morphemes derive from German, Greek and Latin roots. For indexing and retrieval purposes, such a morpheme dictionary may be further structured by defining the semantic relations among morpheme sets in order to build up a multilingual morpheme thesaurus. We present a tool for thesaurus compilation and management, and outline a methodology for the proper construction and maintenance of a multilingual morpheme thesaurus.

Germany↗