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Biomedical subjects

E Hoffmann

Publications and source records attributed to E Hoffmann.

At least 109 records · Page 6Linked to original sources
PubMed1997

The combined transvenous implantation of cardioverter defibrillators and permanent pacemakers.

We developed criteria for implantation and programming of permanent endocardial pacemakers in patients with a nonthoracotomy ICD system. These criteria were prospectively used in 10 patients who recieved an ICD prior to (n = 5) or following (n = 5) implantation of a dual chamber (n = 6) or ventricular (n = 4) pacemaker with a unipolar (n = 4) or bipolar (n = 6) lead configuration. All patients were tested for interactions or malfunctions. Undersensing of ventricular fibrillation by the atrial sense amplifier and inadequate atrial pacing occurred in one patient with a unipolar dual chamber system programmed to AAIR but didn't impair ICD sensing. Transient or permanent loss of capture or sensing of the pacemaker was not observed after ICD shocks with the output programmed to double pulse width and voltage of stimulation threshold and the sensitivity to 50% of the detected R wave. One episode of transient reprogramming occurred without clinical consequences. One unipolar ventricular pacemaker lead had to be exchanged against a bipolar lead because of oversensing of the pacing artifact by the ICD. There was no failure of an ICD to detect ventricular arrhythmias due to inadequate pacemaker activity. During a follow-up period of 21 +/- 11 months, a total of 78 ventricular arrhythmias were effectively treated in six patients. Thus, a combined use of transvenous ICD and pacemaker is possible despite the close vicinity of pacing and defibrillations leads. Optimized programming different to the common settings is required. As interactions occurred only in unipolar pacemaker leads bipolar systems should be used in these patients.

Aged↗
PubMed1997

The positive charge of the imidazole side chain of histidine7 is crucial for GLP-1 action.

Glucagon-like peptide-1(7-36)amide/(7-37) (GLP-1) is an incretin hormone which plays an important role in postprandial glucose homeostasis. Since GLP-1 potentiates glucose-induced insulin secretion, stimulates insulin biosynthesis and inhibits glucagon release, it is a potential tool for the treatment of diabetes mellitus. For this, an exact understanding of the structural/functional moieties of the peptide is mandatory. The present study investigates the importance of structural features of histidine7 at the N-terminus for GLP-1 action. Based upon binding and activity data obtained from ten different GLP-1 analogues we show that not the positive charge of the free alpha-amino group but the positive charge of the imidazole side chain of histidine is crucial for GLP-1 action. The presence of a ring structure and a basic function as well as the correct positioning of both seems to be decisive.

Animals↗
PubMed1997

Pentobarbital decreases the gamma-aminobutyric acidA receptor subunit gamma-2 long/short mRNA ratio by a mechanism distinct from receptor occupation.

Treatment with pentobarbital of primary cultured cerebellar granule cells decreased the gamma-aminobutyric acid, (GABA)A receptor subunit gamma-2 long/short (gamma-2L/S) mRNA ratio. A high dose of pentobarbital (500 microM) decreased the gamma-2L/S ratio by 64%; the decrease was dose and time dependent and reversible. (-)-Hexobarbital (500 microM), the less potent stereoisomer for GABA(A) receptor activation, decreased the ratio slightly (30%) but significantly more than (+)-hexobarbital (20%). Other GABA(A) receptor activators had no (100 mM ethanol) or little (2 microM 5alpha-pregnane-3alpha-ol-20-one) effect on the gamma-2L/S ratio. Furthermore, picrotoxin (10 microM), which blocks the GABA- and pentobarbital-activated GABA(A) receptor channel, neither changed the gamma-2L/S ratio nor blocked the pentobarbital-induced changes. These data suggest that barbiturates alter the gamma-2L/S mRNA ratio by a mechanism that does not require GABA(A) receptor activation. The gamma-2L/S subunit mRNA includes an exon encoding an octapeptide that contains a protein kinase C phosphorylation consensus site. This exon-encoded peptide, occurring in the putative intracellular loop, can be phosphorylated, and in vitro, this phosphorylation has been shown to have functional consequences. This is the first report of a drug-induced alteration in receptor mRNA splicing. Furthermore, the changes in the gamma-2L/S ratio produced by pentobarbital exposure may have significant effects on the function of an important brain protein, the GABA(A) receptor.

Animals↗
PubMed1996

Human bone morphogenetic protein 2 contains a heparin-binding site which modifies its biological activity.

Bone morphogenetic protein 2 (BMP-2) plays a decisive role during bone regeneration and repair as well as during various stages of embryonal development. A cDNA encoding mature human BMP-2 could be efficiently expressed in Escherichia coli, and after renaturation a dimeric BMP-2 protein of M(r) 26,000 was prepared with a purity greater 98%. The recombinant BMP-2 was functionally active as demonstrated by the induction of alkaline phosphatase activity in the C3H10T1/2 fibroblast cell line (EC50 of 70 nM) and proteoglycan synthesis in embryonic chicken limb bud cells (EC50 of 15-20 nM). A peptide 1-17 representing the N-terminal basic part of BMP-2 as well as heparin increased the specific activity of the protein about fivefold in the limb bud assay. These observations suggested that the N-terminai reduce the specific activity of BMP-2, probably by interacting with heparinic sites in the extracellular matrix. This conclusion was supported by a variant EHBMP-2, where the N-terminal residues 1-12 of BMP-2 had been substituted by a dummy sequence of equal length and which showed an EC50 value of around 1 nM which was affected neither by heparin nor by peptide 1-17. A physical interaction between BMP-2 and heparin could be seen in biosensor experiments, where BMP-2 bound to immobilized heparin with a dissociation constant, Kd, of approximately 20 nM, whereas the heparin-binding of variant EHBMP-2 was negligible. These results identify the basic N-terminal domains of dimeric BMP-2 as heparin-binding sites that are not obligatory for receptor activation but modulate its biological activity.

Amino Acid Sequence↗
PubMed1996

Circulating endothelin-1 levels in type 2 diabetic patients with ischaemic heart disease.

To investigate whether circulating endothelin-1 (Et-1) may be related to the increased incidence and severity of ischaemic heart disease in type 2 diabetes mellitus, we compared the concentrations in type 2 diabetic patients and in non-diabetic patients with coronary artery disease (CAD) angiographically documented. Plasma levels of Et-1 were determined in 34 type 2 diabetic patients with CAD (16 with stable angina, 6 with unstable angina, 12 with previous myocardial infarction) and in 19 nondiabetic patients with CAD (4 with stable angina, 5 with unstable angina, 10 with previous myocardial infarction). Fifteen diabetic patients without CAD and 9 healthy volunteers served as control subjects. In the type 2 diabetic patients, the mean Et-1 levels were 3.19 +/- 1.61 pmol/l in those with stable angina, 3.58 +/- 1.92 pmol/l in those with unstable angina, 4.24 +/- 2.53 pmol/l in those with myocardial infarction. These values were not significantly different one another, nor from the values obtained from type 2 diabetic controls (3.64 +/- 2.13 pmol/l). In the non-diabetic patients, the mean Et-1 levels were 3.92 +/- 0.73 pmol/l in those with stable angina, 4.35 +/- 1.67 pmol/l in those with unstable angina, 4.33 +/- 1.66 pmol/l in those with myocardial infarction. These values were not significantly different one another, but significantly higher than those obtained from healthy controls (2.07 +/- 0.67 pmol/l; P < 0.001). No significant differences were found in Et-1 levels between diabetic and non-diabetic patients with stable, unstable angina and previous myocardial infarction. In contrast, a statistically significant difference was found in Et-1 levels between diabetic and non-diabetic control subjects (P < 0.05). In conclusion, similar raised concentrations of Et-1 in diabetic and non-diabetic patients with stable, unstable angina and previous myocardial infarction do not support the hypothesis that higher levels of Et-1 in diabetic patients are responsible for the increased incidence of CAD in diabetes mellitus. However, the raised Et-1 levels found in diabetic patients in the absence of CAD strongly suggest that a generalised endothelial dysfunction, documented in our study by increased levels of Et-1, most probably precedes subsequent cardiovascular diseases.

Aged↗
PubMed1996

Particle analysis of car exhaust by ETV-ICP-MS.

Particulates of platinum group elements (Pt, Rh, Pd, Ir) emitted in automotive catalyst exhaust were measured down to the pg/m(3) level. Samples were taken from a standard type three-way catalyst equipped gasoline engine, running on a computer controlled dynamometer. Particulates in catalyzed car exhaust were sampled fractionated according to size by using the cascade impactor with separate targets mounted underneath each nozzle. The targets, small flat discs made of pure graphite, were subsequently analyzed by ETV-ICP-MS without any preparatory steps.

Journal Article↗
PubMed1996

Differential determination of arsenic (III) and total arsenic with L-cysteine as prereductant using a flow injection non-dispersive atomic absorption device.

Speciation of arsenic in environmental samples gains increasingly importance, as the toxic effects of arsenic are related to its oxidation state. A method was developed for the determination of trace amounts of arsenic (III) and total arsenic by flow injection hydride generation coupled with an in-house made non-dispersive AAS device. The total arsenic is determined after prereduction of arsenic (V) to arsenic (III) with L-cysteine in a low concentration of hydrochloric, acetic or nitric acid. The conditions for the prereduction, hydride generation and atomization were systematically investigated. A quartz tube temperature of 800 degrees C was found to be optimum in view of peak shape and baseline stability. Pb(II), Ni(II), Fe(III), Cu(II), Ag(I), Al(III), Ga(II), Se(IV), Bi(III) were checked for interfering with the 2 microg/L As(V) signal. A serious signal depression was only observed for Se(IV) and Bi(III) at a 150-fold excess. With the above system, arsenic was determined at a sampling frequency of about 1/min with a detection limit (3sigma) of 0.01 microg/L using a 0.5 mL sample. The reagent blank was 0.001+/-0.0003 absorbance units and the standard deviation of 10 measurements of the 2 microg/l As signal was found to be 1.2%. Results obtained for standard reference materials and water samples are in good agreement with the certified values and those obtained by ICP-MS

Journal Article↗
PubMed1996

Investigations of the migration of elements in tree rings by Laser-ICP-MS.

The autocorrelation function of the concentration of elements in growth rings has been used to study their migration from ring to ring. The correlation time which can be calculated by the autocorrelation function gives an indication of the transport of elements. However, a large correlation time might only be taken as a necessary criterion for the migration but not for a sufficient one. Laser sampling-ICP-MS has been used for the determination of the contents of elements in the rings of an 150 years old oak - the autocorrelation functions of selected elements have been calculated. Large correlation times have been only obtained for Ca, Fe and Cr. It may be concluded that Mg, Zn, Cu, Sr, Pb, Ni, Ba, Al and Mn hardly migrate radially in the trunk of an oak.

Journal Article↗
PubMed1996

Analysis of leaves by using the laser ICP-MS with isotope dissolution method.

The use of laser ablation inductively coupled mass spectrometry (laser ICP-MS), in combination with a calibration procedure involving the addition of enriched isotopes, for the determination of trace elements in birch leaves and their ashes is described. Samples are pressed into pellets without binder materials and analyzed using the ICP-MS spectrometer ELAN 5000 with the laser sampler type 320 (Perkin Elmer). The analytical results obtained by two methods are compared with the values obtained after digestion of the same samples and analysis of the resulting solutions by ICP-MS. The results are discussed in terms of precision, accuracy and limits of detections.

Journal Article↗
PubMed1996

Application of Laser-ICP-MS in environmental analysis.

Laser sampling inductively coupled plasma mass spectrometry has been used for the quantitative determination of trace elements in samples of environmental significance. Solid sampling in environmental analysis is a very demanding type of application: in fact, the instrumental conditions must be carefully chosen and optimized to minimize signal fluctuations, the vaporized material introduced into the plasma should be representative to the composition of the whole sample and a suitable calibration method must be developed. The analytical problems addressed are: determination of elements in plant ash and their direct determination in growth rings of oaks.

Journal Article↗
PubMed1996

Determination of metals in airborne particulates by LEAFS and ICP-MS after sampling on reusable graphite filters.

Laser excited atomic fluorescence spectrometry combined with electrothermal atomization (ETA-LEAFS) and inductively coupled plasma mass spectrometry combined with electrothermal evaporation (ETV-ICP-MS) were used to measure the concentrations of some metals in ambient air sampled at the outskirts of Berlin. Using graphite to collect airborne particulates the contents of lead, palladium, and thallium could be determined in the pg/m(3) range.

Journal Article↗
PubMed1996

[The accuracy of angiography and CT angiography of the carotid bifurcation compared to macro-morphological correlation].

PURPOSE: To compare the degree of carotid artery stenosis in angiography and CT angiography with the degree of stenosis measured in an intact eversion endarterectomy specimen. METHODS: Preoperative angiograms (intraarterial DSA, 512 x 512 matrix) and CT-angiograms (24 sec spiral scan, slice thickness 2 mm, pitch 1.5) were taken in 12 patients with symptomatic carotid stenosis. Evaluation of the degree of stenosis was performed according to the NASCET ("distal" degree) and ECST ("local" degree) methods. These data were compared with measurements of the surgical specimens. RESULTS: The median "local" degree of stenosis in angiograms was 81.5% (range: 70-99%), in CT angiograms 83% (59-94%) and in specimens 85.5% (65-96%). The "distal" degree of stenosis was 79% (50-99%) in angiograms, 85.5% (55-99%) in CT angiograms and 81% (52-95%) in specimens. CT angiography slightly overestimated the degree of stenosis compared with the specimen, whereas angiography slightly underestimated the true degree of stenosis. However, these differences were not statistically significant. CONCLUSION: CT angiography is able to predict the degree of internal carotid stenosis when compared with an intact surgical specimen. It is as accurate as the "gold standard" of invasive angiography.

Angiography, Digital Subtraction↗
PubMed1996

Comparison of a unipolar defibrillation system with a dual lead system using an enlarged defibrillation anode.

The unipolar system for transvenous defibrillation, consisting of a single right ventricular lead as the cathode and the device shell as anode, has been shown to combine low defibrillation thresholds (DFTs) and simple implantation techniques. We compared the defibrillation efficacy of this system with the defibrillation efficacy of a dual lead system with a 12-cm long defibrillation anode placed in the left subclavian vein. The data of 38 consecutive patients were retrospectively analyzed. The implantation of an active can system was attempted in 20 patients (group 1), and of the dual lead system in 18 patients (group 2). Both groups had comparable demographic data, cardiac disease, ventricular function, or clinical arrhythmia. The criterion for successful implantation was a DFT of < or = 24 J. This criterion was met in all 18 patients of group 2. The active can system could not be inserted in 3 of the 20 group 1 patients because of a DFT > 24 J. In these patients, the implantation of one (n = 2) or two (n = 1) additional transvenous leads was necessary to achieve a DFT < or = 24 J. The DFTs of the 17 successfully implanted group 1 patients were not significantly different from the 18 patients in group 2 (12.3 +/- 5.7 J vs 10.8 +/- 4.8 J). The defibrillation impedance was similar in both groups (50.1 +/- 6.1 omega vs 48.9 +/- 5.2 omega). In group 1, both operation duration (66.8 +/- 17 min vs 80.8 +/- 11 min; P < 0.05) and fluoroscopy time (3.3 +/- 2.1 min vs 5.7 +/- 2.9 min; P < 0.05) were significantly shorter. Thus, the active can system allows reliable transvenous defibrillation and a marked reduction of operation duration and fluoroscopy time. The dual lead system, with an increased surface area defibrillation anode, seems to be a promising alternative for active can failures.

Defibrillators, Implantable↗
PubMed1996

Regeneration of plant cell protoplasts under microgravity: investigation of protein patterns by SDS-PAGE and immunoblotting.

As part of the D-2 Spacelab mission, tobacco (Nicotiana tabacum L.) protoplasts were cultured for 10 days in microgravity and successfully regenerated into microcalli, which, after further cultivation on the ground, gave rise to intact plants. Protein analysis was performed on samples taken during the initial microgravity period and compared to ground controls. Total protein content and protein patterns were monitored, as well as the cytoskeletal proteins tubulin and actin, a key enzyme of secondary metabolism, phenylalanine ammonia lyase, and the pathogenesis-related protein osmotin. None of the investigated proteins showed a gravity-dependent effect. Since relative changes due to culture age were detectable in the immunoblots as well as in the total protein pattern, an adaptation of the cells to microgravity without major modifications of their protein complement may be assumed.

Actins↗
PubMed1996

Promoter elements in the influenza vRNA terminal structure.

The role of the partially double-stranded influenza vRNA terminal structure and its constitutive elements as a promoter signal was studied in vivo in a series of nucleotide substitution and insertion derivatives. A series of single and complementary double exchanges restoring intrastrand base pairing shows that a distal promoter element consists of a six-base pair double-stranded RNA rod in long-range complementary interaction. Within the distal element, all base pair positions are freely exchangeable, and hence no nucleotide-specific recognition could be identified. The proximal promoter element consists of nine partially complementary nucleotides at the vRNA 5' and 3' end. The nine plus six base pair panhandle rod of protein-free vRNA is interrupted by a central third element, a single unpaired nucleotide: adenosine 10 or various substitute residues, which appears to cause a bulged conformation in the overall structure. Mutagenization studies in the promoter proximal element indicate that, upon binding to polymerase, nucleotides at positions 2 and 3 interact with positions 9 and 8 within each branch (5' or 3') in short-range base pairing. In this conformation, the intermediate positions 4-7 are exposed as a single-stranded tetra-loop, which includes invariant guanosine residue 5 in the top conformational position of the 5' segment loop. Altogether, the three base paired segments in angular conjunction to each other adopt a conformation that is described in a "corkscrew model" for an activated stage of vRNA/polymerase interaction.

Adenosine↗