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Biomedical subjects

J Wiemer

Publications and source records attributed to J Wiemer.

At least 19 recordsLinked to original sources
PubMed2003

Informatics united: exemplary studies combining medical informatics, neuroinformatics and bioinformatics.

OBJECTIVES: Medical informatics, neuroinformatics and bioinformatics provide a wide spectrum of research. Here, we show the great potential of synergies between these research areas on the basis of four exemplary studies where techniques are transferred from one of the disciplines to the other. METHODS: Reviewing and analyzing exemplary and specific projects at the intersection of medical informatics, neuroinformatics, and bioinformatics from our experience in an interdisciplinary research group. RESULTS: Synergy emerges when techniques and solutions from medical informatics, bioinformatics, or neuroinformatics are successfully applied in one of the other disciplines. Synergy was found in 1. the modeling of neurophysiological systems for medical therapy development, 2. the use of image processing techniques from medical computer vision for the analysis of the dynamics of cell nuclei, and 3. the application of neuroinformatics tools for data mining in bioinformatics and as classifiers in clinical oncology. CONCLUSIONS: Each of the three different disciplines have delivered technologies that are readily applicable in the other disciplines. The mutual transfer of knowledge and techniques proved to increase efficiency and accuracy in a manifold of applications. In particular, we expect that clinical decision support systems based on techniques derived from neuro- and bioinformatics have the potential to improve medical diagnostics and will finally lead to a personalized delivery of healthcare.

Computational Biology↗
PubMed2001

Haemodialysis monocytopenia: differential sequestration kinetics of CD14+CD16+ and CD14++ blood monocyte subsets.

In peripheral blood the majority of circulating monocytes present a CD14highCD16- (CD14++) phenotype, while a subpopulation shows a CD14lowCD16+ (CD14+CD16+) surface expression. During haemodialysis (HD) using cellulosic membranes transient leukopenia occurs. In contrast, synthetic biocompatible membranes do not induce this effect. We compared the sequestration kinetics for the CD14+CD16+ and CD14++ monocyte subsets during haemodialysis using biocompatible dialysers. Significant monocytopenia, as measured by the leucocyte count, occurred only during the first 30 min. However, remarkable differences were observed between the different monocyte subsets. CD14++ monocyte numbers dropped to 77 +/- 13% of the predialysis level after 15 min, increasing to > or = 93% after 60 min. In contrast, the CD14+CD16+ subset decreased to 33 +/- 15% at 30 min and remained suppressed for the course of dialysis (67 +/- 11% at 240 min). Approximately 6 h after the end of HD the CD14+CD16+ cells returned to basal levels. Interestingly, the CD14+CD16+ monocytes did not show rebound monocytosis while a slight monocytosis of CD14++ monocytes was occasionally observed during HD. A decline in CD11c surface density paralleled the sequestration of CD14+CD16+ monocytes. Basal surface densities of important adhesion receptors differed significantly between the CD14+CD16+ and CD14++ subsets. In conclusion, during HD the CD14+CD16+ subset revealed different sequestration kinetics, with a more pronounced and longer disappearance from the blood circulation, compared with CD14++ monocytes. This sequestration kinetics may be due to a distinct surface expression of major adhesion receptors which facilitate leucocyte-leucocyte, as well as leucocyte-endothelial, interactions.

CD18 Antigens↗
PubMed2000

Self-organizing maps for visual feature representation based on natural binocular stimuli.

We model the stimulus-induced development of the topography of the primary visual cortex. The analysis uses a self-organizing Kohonen model based on high-dimensional coding. It allows us to obtain an arbitrary number of feature maps by defining different operators. Using natural binocular stimuli, we concentrate on discussing the orientation, ocular dominance, and disparity maps. We obtain orientation and ocular dominance maps that agree with essential aspects of biological findings. In contrast to orientation and ocular dominance, not much is known about the cortical representation of disparity. As a result of numerical simulations, we predict substructures of orientation and ocular dominance maps that correspond to disparity maps. In regions of constant orientation, we find a wide range of horizontal disparities to be represented. This points to geometrical relations between orientation, ocular dominance, and disparity maps that might be tested in experiments.

Algorithms↗
PubMed2000

Learning cortical topography from spatiotemporal stimuli.

Stimulus representation is a functional interpretation of early sensory cortices. Early sensory cortices are subject to stimulus-induced modifications. Common models for stimulus-induced learning within topographic representations are based on the stimuli's spatial structure and probability distribution. Furthermore, we argue that average temporal stimulus distances reflect the stimuli's relatedness. As topographic representations reflect the stimuli's relatedness, the temporal structure of incoming stimuli is important for the learning in cortical maps. Motivated by recent neurobiological findings, we present an approach of cortical self-organization that additionally takes temporal stimulus aspects into account. The proposed model transforms average interstimulus intervals into representational distances. Thereby, neural topography is related to stimulus dynamics. This offers a new time-based interpretation of cortical maps. Our approach is based on a wave-like spread of cortical activity. Interactions between dynamics and feedforward activations lead to shifts of neural activity. The psychophysical saltation phenomenon may represent an analogue to the shifts proposed here. With regard to cortical plasticity, we offer an explanation for neurobiological findings that other models cannot explain. Moreover, we predict cortical reorganizations under new experimental, spatiotemporal conditions. With regard to psychophysics, we relate the saltation phenomenon to dynamics and interaction in early sensory cortices and predict further effects in the perception of spatiotemporal stimuli.

Animals↗
PubMed1999

[When lipids increase in dialysis: the role of heparin! Standard heparin increases, low-molecular-weight heparin lowers triglycerides].

Dyslipoproteinemia in patients on hemodialysis is characterized by a decrease in high density lipoprotein (HDL), cholesterol, hypertriglyceridemia, increased triglyceride-rich lipoproteins, such as very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL), a higher proportion of the small dense low density lipoprotein (small dense LDL) subfraction, and higher lipoprotein(a) concentration. The reason for the changes in triglyceride metabolism is an increase in the production of apolipoprotein B, and a decrease in the metabolism of VLDL as a consequence of decreased endothelial cell delipidation. The endothelial lipoprotein lipase, which plays a major role in this process, is released by heparin, which is essential for the function of the enzyme. Repeated administration of heparin for anticoagulation during hemodialysis apparently leads to an LPL depletion in the endothelium. This results in further exhaustion of lipolysis. Clinical studies in hemodialysis patients with high triglyceride and cholesterol levels indicate that a change from standard heparin to low-molecular-weight heparin improves the lipid profile by lowering triglycerides and cholesterol.

Cholesterol↗
PubMed1999

Extracellular matrix structure after heart transplantation.

Following heart transplantation remodeling of the donor heart causes changes in the extracellular myocardial matrix. We investigated 20 right ventricular endomyocardial biopsies taken 17+/-4 days (group I, n=9) and 63+/-13 days (group II, n=11) after heart transplantation from 16 patients transplanted for end-stage cardiomyopathy (15 dilated/1 ischemic). Immunohistochemical staining for collagen I, collagen III, collagen IV, and fibronectin was used. Evaluation was performed at a magnification of 400x using a computer-assisted image analyzing system measuring the relative area stained by the immunoperoxidase method, the number of cells in the given area, and the total area. Collagen I per cell was 13.9+/-5.9 microm2 in group I and increased significantly 66+/-13 days after heart transplantation in the perimysium around the myocardial cells as well as in the endocardium to 49.9+/-15.1 microm2 (P<0.05). No quantitative change in collagen III was noted (75.7+/-12.4 versus 75.5+/-16.0 microm2 n.s.). Collagen IV was found in the perimysial, in the capillary bed and in the vascular network. Significant quantitative change in the amount of collagen IV was not found (64.1+/-12.6 versus 61.0+/-8.9 microm2). Fibronectin was found in the entire perimysial extracellular matrix and in the endocardium in relationship with collagen I and III. An increased amount of fibronectin from 87.09+/-9.9 microm2 (group I) to 140.8+/-17.9 microm2 (group II, P<0.05) was found. The cell area and cell diameters were not significantly different (group I; cell area 772+/-227 microm2, diameter 31.3 microm; group II; cell area 776+/-224 microm2, diameter 31.4 microm). It is concluded that remodeling of the donor heart after transplantation is characterized by a specific increase in collagen I and fibronectin, whereas a change in other collagen subtypes was not observed.

Analysis of Variance↗
PubMed1997

Variations of segmental endothelium-dependent and endothelium-independent vasomotor tone after cardiac transplantation (qualitative changes in endothelial function).

Endothelial dysfunction is a common phenomenon after cardiac transplantation. However, qualitative differences in endothelial vasoregulation at different coronary segments and at different postoperative times have rarely been explored. To uncover the functional variations of endothelium responses we infused the endothelium-dependent vasodilator acetyl-choline (50 micrograms) followed by the endothelium-independent vasodilator 3-morpholinosydnonimine (SIN-1) (1 mg; 16 patients) or nitroglycerin (0.3 mg; 14 patients) sequentially into the left coronary artery. We investigated the responses of 120 nonstenotic coronary segments (proximal and distal left anterior descending and right circumflex coronary arteries) in 30 patients with quantitative angiography (group 1: 13 patients, 12 +/- 1 months after cardiac transplantation; group 2: 17 patients, 55 +/- 3 months after cardiac transplantation). Continuous-flow measurement was performed to exclude significant reduction of microvascular response influencing epicardial dilation. Five responses to acetylcholine administration followed by nitrates were observed. On the one end of the spectrum, segments dilate to acetylcholine administration with no further dilation to exogenous nitric oxide, indicating completely preserved endothelial function. On the other end, segments constrict to acetylcholine with no change after endogenous nitric oxide, reflecting a defective endothelial and defective smooth muscle function. The different patterns of coronary vasomotor lone responses to endogenous nitric oxide followed by exogenous nitric oxide represent different degrees of endothelial function after cardiac transplantation. In addition, the functional assessment of endothelial integrity shows qualitative time-dependent differences between proximal and distal coronary parts. The existence of coronary segments with functioning endothelium indicates that the latter is not diffusely disturbed in all cardiac transplant recipients and that the endothelial damage is perhaps not irreversibly lost.

Acetylcholine↗
PubMed1996

[Multiplicity of clinical symptoms and manifestations of unruptured aneurysms of the sinus of Valsalva--3 case reports].

Sinus Valsalva aneurysms belong to the less common congenital or acquired structural cardiac anomalies. However, in patients with known cardiac anomalies and uncertain or uncharacteristic cardiac symptoms the existence of a sinus Valsalva aneurysm must be taken into consideration. A sinus Valsalva aneurysm can be clinically silent as in the case of the 56-year-old patient with an accompanying bacterial endocarditis. An increasing aortic regurgitation after dilatation of a coarctation of the aorta can also proceed with an ecstasy of the ascending aorta and an aneurysm of the sinus Valsalva (case 2). Furthermore, a rapid dilatation of a non-ruptured sinus Valsalva aneurysm can cause a severe compression of coronary arteries with subsequent myocardial infarction, as in the 27-year-old patient with congenital aortic stenosis and acute endocarditis in case 3.

Adult↗
PubMed1992

Biochemical and immunological properties of urinary angiotensinase A and dipeptidylaminopeptidase IV. Their use as markers in patients with renal cell injury.

Dipeptidyl peptidase IV (EC 3.4.14.5) and angiotensinase A (EC 4.4.11.7) were purified to homogeneity from pooled urine concentrate of patients with renal damage, using ultrafiltration, ammonium sulphate precipitation, lectin affinity chromatography, FPLC-ion-exchange(Mono-Q-)chromatography, and FPLC-gel filtration (Superdex). Based on the specific enzyme activity of the starting material, dipeptidyl peptidase IV was enriched 1629 fold, angiotensinase A 1183 fold. The relative molecular masses, Michaelis constants and isoelectric points were determined. Negative staining of the purified enzymes revealed globular proteins (5-7 nm). Antisera raised against dipeptidyl peptidase IV and angiotensinase A reacted specifically with tubular and, in the case of anti-angiotensinase A sera, with tubular and glomerular structures. In addition, urinary membrane vesicles of proximal tubule origin were eluted with the void volume (Superdex-gel filtration), indicating heavy epithelial cell disintegration. Both soluble tissue enzymes (dipeptidyl peptidase IV, angiotensinase A) and vacuolar blebs shed from epithelia contribute to proteinuria, as was shown in patients with glomerulonephritis, interstitial nephritis, diabetic nephropathy and, for angiotensinase A, in patients with essential arterial hypertension.

Adolescent↗
PubMed1990

Isolation and partial characterization of angiotensinase A and aminopeptidase M from urine and human kidney by lectin affinity chromatography and high-performance liquid chromatography.

Angiotensinase A (ATA) and aminopeptidase M (APM) were partially purified from human urine specimens and human kidney particles using wheat germ lectin affinity chromatography, anion-exchange Fast Protein Liquid Chromatography (FPLC) (Mono Q), chromatofocusing (Mono P, FPLC) and Superose 12 gel filtration. APM, a globular 5-nm glycoprotein, is localized in the brush border membrane of the proximal tubule; angiotensin II-degrading ATA is present on glomerular endothelia and podocytes and, to lesser extent, in the brush border. For the first time, both peaks of ATA and APM activity from urine samples were separated by the above-mentioned techniques with only slight overlap; ATP (146,000 dalton: pI4.8) was enriched more than 20-fold and APM (153,000 dalton, pI4.7) more than 50-fold compared with the activity of the starting material. Using similar separation steps, ATA and APM solubilized from kidney particles could not be resolved into two distinct peak fractions, however, except after hydrophobic interaction chromatography. Thus urine is a major source for the preparation of individual ATA and APM fractions, necessary to generate specific anti-enzyme antibodies for diagnostic purposes.

Aminopeptidases↗
PubMed1987

Photoelectric recording of mechanical responses of cardiac myocytes.

A method to monitor contraction of isolated myocytes by transmicroscopic photometry is illustrated. Two photodiodes are mounted inside an inverse microscope used for visual control of a cell. Illumination of one diode varies in proportion to changes in cell length. The contraction signal is amplified in a comparator circuit. Spatial resolution of the device is in the order of 1 micron which corresponds to about 5% of cell shortening in the fully activated state of contraction. The method was tested on isolated myocytes from guinea-pig ventricle. Optical records of contraction in response to action potentials or during voltage clamp compare well with the contractile behavior of multicellular preparations.

Action Potentials↗
PubMed1984

Effects of the new cardiotonic agent sulmazole on the slow inward current of sheep cardiac Purkinje fibres.

The new cardiotonic agent 2-[(2-methoxy-4-methylsulfinyl)-phenyl]-1H-imidazo[4,5-b]pyridine (sulmazole, AR-L 115 BS) has marked positive inotropism but causes a depression in the plateau phase of the action potential of cardiac Purkinje fibres. This loss of plateau is known to occur with calcium antagonists which reduce contractility. In order to identify the mechanism underlying this possibly controversal effect the slow (calcium dependent) inward current (isi) was measured using the double microelectrode voltage clamp technique. In this current system, sulmazole was observed to have a slight effect on the inactivation parameter f infinity of isi by shifting it in hyperpolarizing direction. This increase in inactivation was considered when isi was determined. However, isi itself is reduced quite considerably and the linear instantaneous current voltage relationship is shifted to negative potentials. The kinetics of activation (d infinity) are not affected by sulmazole. From the more or less parallel shifts of isi we conclude that the reversal potential of isi is decreased which in turn strongly indicates an increase of intracellular calcium ion concentration. The reduction of isi by sulmazole is not the result of a specific membrane effect as in the case of some calcium antagonists. Sulmazole does not generate its positive inotropism by way of an increased slow inward current as do beta-adrenoceptor agonists but rather reduces the slow inward current by means of a negative shift of Eisi and a decrease in isi-driving force after it has affected intracellular calcium.

Animals↗
PubMed1984

The response of the calcium dependent myocardial contractility to the new cardiotonic agent sulmazole.

In vitro and in vivo animal experiments to test the positive inotropism of 2-[(2-methoxy-4-methylsulfinyl)-phenyl]-1H-imidazo[4,5-b]pyridine (sulmazole, AR-L 115 BS) have shown increases of contractility of up to 220% in the mmol/l concentration range. Comparative studies designed to attribute to sulmazole mechanisms established for other positive inotropic drugs have been negative for digitalis and beta-adrenoceptor agonists but showed slight similarities to xanthine derivatives. To explore the yet unknown mode of action of sulmazole we investigated the interaction between sulmazole and non-humoral/non-drug interventions for positive inotropism in vitro. Peak tension obtained in solutions varying in calcium content between 0.36 and 7.2 mmol/l Ca2+ were normalized with respect to the tension measured at standard 1.8 mmol/l Ca2+ for control and sulmazole treated preparations (sheep interventricularis cordis muscle and guinea pig papillary muscle). Double logarithmic plots of normalized tension versus calcium concentration were linear and superimposable for control, 10(-4), and 10(-3) mol/l sulmazole. In depleted sodium solutions (choline substitution) normalized peak tension of control and 10(-4) mol/l sulmazole containing solutions did not significantly differ. In length-tension plots sulmazole behaved as did increased extracellular calcium. We assume that the positive inotropism of sulmazole is primarily due to a displacement of calcium at non-specific ligand sites within the protein matrix of the cytosol which effectively raises the apparent intracellular calcium activity.

Animals↗
PubMed1983

The influence of a new cardiotonic drug, acrihellin, on sinus node and the current underlying pacemaker activity of cardiac Purkinje fibres.

The spontaneous beating frequency of guinea pig sino-atrial preparations was observed under the influence of 3 beta, 5, 14-trihydroxy-19-oxo-5 beta-bufa-20,22-dienolide-3-(3-methylcrotonate (D 12316, acrihellin), a new cardiotonic drug. There was a slight acceleration of spontaneous frequency after administering rather high doses (10(-6) mol/l) of the drug. Voltage clamp experiments were performed in sheep cardiac Purkinje fibres. AcriheLlin strongly affected the current underlying pacemaker activity, ik2. The kinetic parameter s infinity of this current system was shifted in the hyperpolarizing direction by 4-13 mV. The amplitude of the pacemaker current in Purkinje fibres was reduced by up to 25% in voltage clamp experiments, but the reversal potential and the inward going rectification were left unchanged. After exposure to adrenaline (epinephrine) the well-known depolarizing shift of s infinity was partially restored by acrihellin. This can be interpreted as an antiadrenergic effect of the drug similar to that of beta-adrenoceptor antagonists. However, beta-blockers do not affect the pacemaker kinetics of fibres untreated with adrenaline as does acrihellin. This suggests that the interplay of acrihellin and adrenaline is not that of an agonist and antagonist at a membrane receptor but rather the overlapping of two separate membrane effects.

Animals↗
PubMed1983

Effects of acrihellin on cardiac contractility in comparison to various inotropic interventions.

The inotropic effects of the new cardiotonic drug 3 beta,5,14-trihydroxy-19-oxo-5 beta-bufa-20,22-dienolide-3-(3-methylcrotonate) (D 12316, acrihellin) were investigated using twitch contractions time to peak and twitch lengths did not change. Peak tension increased by 140% on an average in 12 experiments at 10(-6) mol/l (acrihellin). In the dose-response curve half maximal positive inotropism occurred at approx. 10(-7) mol/l. Experiments on length tension relationships of resting and twitch tension confirmed that resting tension does not change at any stretch length after administering acrihellin. The position Lmax of maximal twitch contraction force also was not changed but in normalized length-tension cones the positive slope region showed an increase relative to maximal tension which is a feature of positive inotropic interventions. Measurements of contractility in various external calcium solutions between 0.45 mmol/l and 7.2 mmol/l gave evidence that the response of contraction force of fibres exposed to acrihellin to variation of external calcium differs from untreated fibres which respond more strongly. This behaviour of the cardiosteroid acrihellin was very similar to that of adrenaline (epinephrine) whereas digoxin and ouabain did not affect the response of twitch force to changes in external calcium.

Animals↗
PubMed1983

Voltage clamp study of the action of the new cardiotonic compound acrihellin on fast and slow inward currents in cardiac Purkinje fibres.

The action of 3 beta,5,14-trihydroxy-19-oxo-5 beta-bufa-20,22-dienolide-3-(3-methylcrotonate) (D 12316, acrihellin) on the fast and slow inward currents of sheep cardiac Purkinje fibres was analyzed by means of a conventional double microelectrode voltage clamp technique. Acrihellin diminished action potential duration and the plateau phase. Effective refractory periods were shortened in relation to the decrease in action potential duration. The upstroke velocity was slightly decreased; a systematic study of dV/dtmax, however, did not reveal any specific local anaesthetic side-effect of the drug. The decrease in the plateau phase of the action potential was due to a reduction in time-dependent slow inward current. The kinetics and the reversal potential of the slow inward current was not affected by acrihellin, but only the current voltage relationship, which was decreased.

Action Potentials↗
PubMed1982

Tl+-ions: influence on cardiac contractility.

Attention has recently focussed on the heavy metal thallium as an environmental contaminant of increasing importance. From accidental or suicidal ingestions of thallium it has been known for many years that cardiovascular disorders regularly emerge, and for this reason, a variety of investigations of cardiological interest have been conducted. Amongst these, the effects of thallium on the contractile force of isolated myocardial tissues have been studied. Previous experiments were all carried out at concentrations far beyond those encountered during intoxication and yielded controversal data. We therefore reinvestigated the effects of thallium on myocardial tissue at levels between l0(-8) and 10(-3) M, thus covering the range of thallium concentrations encountered after uptake from a polluted environment through those seen after unintentional or intentional ingestion to levels at which previous studies were performed. Sheep interventricular cordis muscles were used at a stimulation frequency of 0.4 Hz showing three types of responses to thallium exposure. From a total of 32 experiments in 15% of all cases thallium caused a persistent increase in contractility which tended to decrease with time and thallium concentration but always remained greater than the control value. 50% of the experiments showed a progressive loss of contractile force with time and thallium concentration, despite transient increases in contractility which lasted for only 2-5 min after the application of each new thallium concentration. A combination of these types of reaction was observed in the remaining experiments in that a low thallium concentrations myocardial contractility increased considerably but then decreased progressively with time and thallium concentration. Guinea pig papillary muscles were used to test one thallium concentration only for up to 75 min. At 10(-8) M there was no effect, at 10(-7), 10(-6), 10(-5) M Tl+ there were positive inotropic transients followed by an inotropic decay; at 10(-4) M Tl+ only a progressive decrease of contractility was observed. The relationships between time and thallium concentration at different rates of stimulation were examined in two series of experiments at 0.1, 0.2, 0.4, 1.0, and 2.0 Hz. The effects of thallium were accelerated with increased beating rate and the decay of contraction also proceeded to markedly lower levels. In the rested state, thallium was also very effectual; this was illustrated in two series of experiments in which after 10 min intervals of quiescency 15 or more test stimuli were applied at different beating rates (0.1 to 2.0 Hz). The configurations of the resulting staircase phenomena were analyzed with respect to control behavior for each frequency of the test stimuli and for each thallium concentration. These results suggested an involvement of the slow inward current. The steady state values after quiescency showed a pronounced thallium-induced decay similar to that obtained at high constant stimulation rates...

Animals↗