Biomedical subjects

M Wiedemann

Publications and source records attributed to M Wiedemann.

At least 19 recordsLinked to original sources

PubMed2006

Microgravity dependence of excitable biological and physicochemical media.

Neuronal tissue and especially the central nervous system (CNS) is an excitable medium. Self-organisation, pattern formation, and propagating excitation waves as typical characteristics in excitable media consequently have been found in neuronal tissue. The properties of such phenomena in excitable media do critically depend on the parameters (i.e., electromagnetic fields, temperature, chemical drugs) of the system and on small external forces to which gravity belongs. The spreading depression, a propagating excitation depression wave of neuronal activity, is one of the best described of the those wave phenomena in the CNS. Especially in the retina as a true part of the CNS it can be easily observed with optical techniques due to the high intrinsic optical signal of this tissue. Another of such waves in neuronal tissue is the propagating action potential in nerve fibres. In this paper, data from our laboratories concerning the influence of gravity on the velocity of propagating waves in excitable media are summarized mainly in terms of the retinal spreading depression and propagating action potentials. Additionally, we have used waves in gels of the Belousov-Zhabotinsky reaction as the physicochemical model system of biological activity as the properties of these waves follow the same theories as the spreading depression and action potentials and they have some striking similarities in wave behavior. Thus propagating Belousov-Zhabotinsky waves are described by their gravity dependence.

Action Potentials↗

PubMed2001

The mouse Fgfrl1 gene coding for a novel FGF receptor-like protein.

The mouse Fgfrl1 gene codes for a novel cell surface protein that is closely related to the family of the FGF receptors. It contains three extracellular Ig C2 loops and an acidic box, which share 29-33% sequence identity (48-50% similarity) with FGF receptors 1-4. The intracellular portion of the novel protein, however, lacks a tyrosine kinase domain required for signal transduction by transphosphorylation. The gene for Fgfrl1 comprises six exons and is located on mouse chromosome 5 in close proximity to the Idua gene for L-iduronidase.

Amino Acid Sequence↗

PubMed2001

[A new combined surgical interventional method for univentricular palliation of congenital heart defects].

UNLABELLED: Total cavo-pulmonary anastomosis is frequently performed to palliate patients with a broad variety of congenital heart defects with functionally univentricular hearts precluding biventricular circulation. In patients with risk factors for primary repair a stepwise approach is frequently chosen with initial creation of an aorto-pulmonary shunt followed by a Glenn anastomosis or hemifontan procedure. Finally a total cavo-pulmonary connection is completed surgically. The aim of this feasibility study was to develop a combined surgical-interventional approach for creation of a total cavo-pulmonary anastomosis which reduces the number of surgical interventions, precludes extracorporeal circulation and intracardiac sutures, putting the patients at risk for subsequent rhythm disturbances. METHODS: A Glenn anastomosis was created in 10 sheep without cardio-pulmonary bypass. The superior vena cava was banded superior to the cavo-atrial junction leaving a minimal lumen for subsequent interventional balloon dilatation and implantation of a stent graft. A 15 mm Gore-Tex tube was sutured around the inferior vena cava intrapericardially to provide resistance for subsequent interventional stent implantation. Total cavo-pulmonary anastomosis was completed interventionally by dilating the banded vena cava superior and connection of the inferior vena cava to the superior vena cava by implanting an Aneurx covered stent graft. RESULTS: All animals survived the combined surgical-interventional procedure. Stent deployment was possible without causing obstruction to the hepatic veins. Neither stent dislocation nor rhythm disturbances were encountered. CONCLUSIONS: Total cavo-pulmonary anastomosis can be achieved without intracardiac sutures and cardio-pulmonary bypass by use of a combined surgical-interventional approach using the Aneurx covered stent graft.

Animals↗

PubMed2001

Control of the excitability of neuronal tissue by weak external forces.

The spreading depression (SD) is a pronounced example of excitation-depression waves in excitable media, to which neuronal tissue according to its structure and functions belongs. SD waves can especially easily be observed in the vertebrate retina which is neuronal tissue and a true part of the central nervous system (CNS). According to the high intrinsic optical signal (IOS) concomitant with the retinal spreading depression (rSD), it can be monitored with standard video imaging techniques, thus the retina has been used in our studies as a suitable model system for neuronal tissue in general. In particular, the control of wave set-up and propagation in excitable media by weak external forces is of high interest. Accordingly, the interaction of rSD waves with DC and AC electromagnetic fields of low amplitude and frequency and with gravity has been investigated in this study. The dependence of rSD-wave propagation velocity on the given parameters as one important indication of excitability control has been investigated in detail. Our results with rSD waves are partially compared to another well known excitable medium, the Belousov-Zhabotinsky reaction, where some data about the effects of electrical fields and gravity have already been published.

Animals↗

PubMed2000

Characterization of a novel protein (FGFRL1) from human cartilage related to FGF receptors.

Utilizing a subtractive cDNA cloning approach we have identified a novel protein from human cartilage. This protein represents an integral membrane protein with 504 amino acids and a molecular mass of 55 kDa. It is composed of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. The extracellular domain is closely related to the extracellular domain of FGF receptors. The intracellular domain, however, does not show any similarity to the protein tyrosine kinase domain of FGF receptors. The novel gene (FGFRL1) is located on human chromosome 4 band p16 in close proximity to the gene for FGFR3. Its mRNA is preferentially expressed in cartilaginous tissues. Owing to the structural similarity, it is conceivable that the novel protein plays a role in the modulation of FGF receptor activity.

5' Untranslated Regions↗

PubMed1999

Lubeluzole shows neuroprotective effects in an "in-vitro"-model for neuronal lesions in the chicken retina.

In this study, the isolated chicken retina was used as an "in-vitro"-model for investigation of neuronal lesions to show the neuroprotective effects of lubeluzole. Lubeluzole is a neuroprotective compound that has been shown to stereoselectively rescue sensorimotor function and reduce infarct size in photochemical stroke models in rats. In the retina, the typical cell swelling of a developing lesion is accompanied by a very strong intrinsic optical signal (IOS), occurring simultaneous with the electrical signal which is based on changes in light scattering. In the presented model, lesions were elicited electrically with a tungsten microelectrode (0.1 MOmega). The degree of damage was evaluated with optical methods by measuring area and brightness of the affected tissue. Lubeluzole was much more effective in reducing the growth of the lesions than its R-isomer. However, both compounds enhanced the possibility of the neuronal tissue to recover after excitotoxic stimuli.

Animals↗

PubMed1999

Biphasic effects of melatonin on the propagation of excitation waves in the chicken retina.

The retinal spreading depression (SD) is a propagating wave in an excitable medium, the neuronal tissue of the retina. Its velocity is about 3 mm/min and it is accompanied by a variety of changes in the tissue, including electrical and optical events. The pronounced intrinsic optical signal (IOS) of the retinal SD makes it an extremely versatile tool for the investigation of the action of drugs on neuronal tissue and more specific on propagating excitation waves in neuronal tissue. Furthermore, in the last decade increasing evidence has been collected, which shows that SD waves are the basic mechanism of the aura in classical migraine. We have investigated the influence of melatonin on the propagation of retinal SD waves as it has been postulated to have protective effects on neuronal tissue. The results demonstrate that melatonin indeed slows down the retinal SD, however, only in a defined concentration range. Additionally, it changes the IOS of the wave.

Animals↗

PubMed1999

Beta blockers: evidence versus wishful thinking.

Catecholamines and ischemia play an important role in the induction of ventricular tachyarrhythmias. Beta blockers antagonize the effect of catecholamines and have anti-ischemic properties. Several controlled studies performed in the early 1980s in patients after myocardial infarction have shown that beta-blocker therapy clearly decreases sudden and nonsudden cardiac death. Despite the lack of recent randomized trials, data from uncontrolled studies suggest that the beneficial effect of beta blockers is still present in the thrombolytic era. Thus, it is incomprehensible that today in the United States and in most parts of Europe, < 40% of post-myocardial infarction patients are treated with beta blockers. Even in patients with documented sustained ventricular tachycardias (VTs) or ventricular fibrillation (VF), clinical studies indicate that beta blockers improve survival. Thus, even in the thrombolytic era, beta blockers should be used as a basic therapy in patients who are at risk of sudden cardiac death.

Adrenergic beta-Antagonists↗

PubMed1999

Healthcare systems--an international review: an overview.

Based on the source of their funding, three main models of healthcare can be distinguished. The first is the Beveridge model, which is based on taxation and has many public providers. The second is the Bismarck 'mixed' model, funded by a premium-financed social insurance system and with a mixture of public and private providers. Finally, the 'Private Insurance model' is only in existence in the US. The present report explores the impact of these healthcare models on the access to, quality and cost of healthcare in selected European countries. Access is nearly 100% in countries with a public provider system, while in most of the 'mixed' countries, the difference from 100% is made up by supplementary private insurance. No differences are seen between public and mixed provider systems in terms of quality of care, despite the fact that the countries with the former model spend, in general, less of their Gross National Product on healthcare. The Private Insurance/private provider model of the US produces the highest costs, but is lowest in access and is close to lowest ranking in quality parameters.

Delivery of Health Care↗

PubMed1998

Molecular cloning of avian matrix Gla protein.

Matrix Gla protein plays an essential role in preventing the calcification of blood vessel walls, cartilage and other tissues. We report here the primary structure of chicken matrix Gla protein as deduced from the cDNA sequence. The avian protein exhibited the characteristic motifs previously identified in the mammalian proteins, but its amino acid sequence shared only 51-56% identity with the latter proteins. Moreover, a region proposed to function as binding site for gamma-carboxylase in the mammalian proteins was poorly conserved in the chicken protein. Our sequence data should be helpful in the design of mutational analyses which are intended to characterize functional interactions of matrix Gla proteins with other proteins.

Amino Acid Sequence↗

PubMed1998

End-stage renal disease treatment: a European perspective.

There is presently much debate about the optimal flow chart of pre-end-stage renal disease (ESRD) and ESRD patients. This article summarizes two important nonmedical factors that affect the outcome of ESRD patients in Europe: late referral and the structure of the health care system. In a European survey, 30% of patients were referred to a nephrologist less than 1 mo before the start of renal replacement therapy (RRT). This had an impact on the modality choice, as 77.5% of late versus 51.1% of early referrals were started on hemodialysis. Hospitalization at start of RRT was longer in late versus early referrals (15.1 +/- 16.0 versus 27.8 +/- 23.7 d respectively, P < 0.001). There were more patients without antihypertensive medication in the late referral group (28.6% versus 15.5%, P = 0.004), and diastolic BP in this group was higher (83.5 +/- 15.8 versus 74.4 +/- 15.0 mmHg, P = 0.03). One year after the start of dialysis, the number of deaths in the late referrals was higher (26.7 versus 16.4%, P = 0.07) and the number of transplanted patients was lower (4.7 versus 17.5%, P = 0.02). Creatinine clearance at start of RRT was 7.0 +/- 3.5 ml/min in the patients who died during the first year after start of RRT versus 9.5 +/- 3.6 ml/min in those surviving. Only 18% of patients were started with a creatinine clearance > 10 ml/min, as recommended by the Dialysis Outcomes Quality Initiative guidelines. It is concluded that late referral to a nephrologist is still a major problem that has a negative influence on modality choice for peritoneal dialysis, and on morbidity and mortality of ESRD patients.

Europe↗

PubMed1997

The chicken retina as an experimental model for investigation of central nervous lesions.

The aim of this study was to establish an experimental model to investigate neuronal lesions. The retina is an easy accessible model system to study central nervous system (CNS) disorders or neuronal effective drugs. It consists of only a few characteristic layers and is easy to prepare as an intact piece of tissue. In the retina the typical cell swelling of a developing lesion is accompanied by a very strong intrinsic optical signal (IOS) which is simultaneous with the electrical signal and is based on changes in light scattering. The IOS can be easily observed during the whole experiment and can be recorded with non-invasive optical methods for further quantification of damage. In the developed model, the lesions are elicited electrically with a tungsten microelectrode (0.1 M[omega]). The degree of damage depends on the magnitude of the stimulus. The parameters for the quantification of damage are the area and the brightness of the affected tissue. The growth of the lesions can be influenced with drugs added to the perfusion system. In the present study we tested, glycerol, mannitol and ketamine which are known to be neuroprotective in other animal models.

Animals↗

PubMed1997

Platelet activation and signal transduction by convulxin, a C-type lectin from Crotalus durissus terrificus (tropical rattlesnake) venom via the p62/GPVI collagen receptor.

Convulxin, a powerful platelet activator, was isolated from Crotalus durissus terrificus venom, and 20 amino acid N-terminal sequences of both subunits were determined. These indicated that convulxin belongs to the heterodimeric C-type lectin family. Neither antibodies against GPIb nor echicetin had any effect on convulxin-induced platelet aggregation showing that, in contrast to other venom C-type lectins acting on platelets, GPIb is not involved in convulxin-induced platelet activation. In addition, partially reduced/denatured convulxin only affects collagen-induced platelet aggregation. The mechanism of convulxin-induced platelet activation was examined by platelet aggregation, detection of time-dependent tyrosine phosphorylation of platelet proteins, and binding studies with 125I-convulxin. Convulxin induces signal transduction in part like collagen, involving the time-dependent tyrosine phosphorylation of Fc receptor gamma chain, phospholipase Cgamma2, p72(SYK), c-Cbl, and p36-38. However, unlike collagen, pp125(FAK) and some other bands are not tyrosine-phosphorylated. Convulxin binds to a glycosylated 62-kDa membrane component in platelet lysate and to p62/GPVI immunoprecipitated by human anti-p62/GPVI antibodies. Convulxin subunits inhibit both aggregation and tyrosine phosphorylation in response to collagen. Piceatannol, a tyrosine kinase inhibitor with some specificity for p72(SYK), showed differential effects on collagen and convulxin-stimulated signaling. These results suggest that convulxin uses the p62/GPVI but not the alpha2beta1 part of the collagen signaling pathways to activate platelets. Occupation and clustering of p62/GPVI may activate Src family kinases phosphorylating Fc receptor gamma chain and, by a mechanism previously described in T- and B-cells, activate p72(SYK) that is critical for downstream activation of platelets.

Amino Acid Sequence↗

PubMed1997

Transcription of DmRP140, the gene coding for the second-largest subunit of RNA polymerase II.

To analyze transcriptional control regions of Drosophila melanogaster housekeeping genes, we have characterized the promoter of the gene coding for the second-largest subunit of RNA polymerase II (DmRP140). Upstream of DmRP140 the genomic region harbors a gene which is transcribed in the opposite direction (DmRP140up). By determination of the transcription start sites of both genes we found a short non-transcribed intergenic region of 220 bp. Functional analysis of various promoter reportergene constructs by transient transfection of cultured cells revealed that sequences important for transcription of DmRP140 are located in the untranslated leader of the upstream gene. The onset of DmRP140 transcription during embryonic development was studied in transgenic flies using beta-galactosidase as reportergene. To distinguish between the maternally provided DmRP140 transcripts and the embryonically transcribed RNA the offspring of nontransformed females and male transformants was examined. The development of a sensitive detection assay based on a chemiluminescent substrate for beta-galactosidase allowed us to determine the onset of DmRP140 transcription to between 8-10 h after oviposition. Thus, DmRP140 transcription does not start following the transcriptional transition period between 2-3 h of development but occurs much later in embryogenesis coinciding with decreasing DNA synthesis and cell division rates.

Animals↗

PubMed1997

Exogenous application of gangliosides changes the state of excitability of retinal tissue as demonstrated by retinal spreading depression experiments.

Gangliosides are amphiphilic, sialic acid-containing glycosphingolipids which are found preferentially in complex composition in the cellular membranes of the nervous system of vertebrates, including the vertebrate retina as well as in other membranes. They are always exposed to the extracellular side of the membranes. By virtue of the negative charges they carry at their headgroup, they contribute to the surface charge of the membrane and may affect ion distribution, mainly that of protons and calcium ions, at the outer side of the membranes. Using retinal spreading depression (RSD) as a tool, we show in this study that the addition of exogenous gangliosides to the extracellular space can change the state of excitability of the retinal tissue. In RSD experiments it reduces the propagation velocity as well as the intrinsic optical signal of RSD waves. These effects are concentration dependent (IC50 about 20 microM) and increase with the increasing negative charge of the ganglioside headgroup. As a possible mechanistic basis of the changes found, the change of the calcium homeostasis of the extracellular space by the exogenously added gangliosides is discussed. Gangliosides have been reported to be useful in the treatment of some neuropathological syndromes, including migraine, although experimental verification has not been possible up to now. Taking into account that the retina is a true part of the CNS, our data may be interpreted as the requested verification.

Animals↗

PubMed1997

The mode of onset of ventricular tachycardia. A patient-specific phenomenon.

AIMS: The purpose of our study was to investigate the electrical trigger modes of monomorphic ventricular tachycardia, by analysing stored intracardiac electrograms, and to identify haemodynamic or electrocardiographic predictors in patients with cardioverter-defribrillators. METHODS: We recorded 286 episodes of monomorphic ventricular tachycardia in 38 patients with at least three events. The electrical triggers were characterized by the morphology number, complexity, and coupling interval of premature depolarizations preceding the ventricular tachycardia. We also evaluated clinical and electrocardiographic data. RESULTS: We found two basic electrical trigger modes. Two hundred and sixteen events (75%) were observed to have no RR-interval variations before onset, while 70 episodes (25%) had a short-long-short sequence. These episodes invariably featured increased QT disperson. In 31 of 38 patients (82%), the ventricular tachycardias were always initiated by the same mode of onset. In eight patients, the monomorphic ventricular tachycardias were always triggered by short-long-short sequences. In seven patients, more than one onset mechanism was observed. CONCLUSIONS: Two basic modes of onset were responsible for monomorphic ventricular tachycardia: one without RR-interval variations immediately prior to onset and another characterized by short-long-short sequences and increased QT dispersion. The mechanisms were largely patient-specific and not related to cardiac diagnosis or left ventricular function.

Adult↗

PubMed1996

Effects of antimigraine drugs on retinal spreading depression.

It has been suggested that spreading depression may play a role in triggering classical migraine. In this study the retinal spreading depression was used as a pharmacological tool to test the neuronal effects of several common antimigraine drugs. As the chicken retina is void of any blood vessels the observed effects must be of pure neuronal origin. It is shown that propranolol, sumatriptan, methysergide, paracetamol and acetylsalicyclic acid decrease the propagation velocity of retinal spreading depression waves, accelerate the recovery of the optical and electrical signal and reduce the amplitude of the negative potential shift, concomitant with the spreading depression. Barbiturate increases the spreading velocity, and the amplitude of the potential shift. Ergotamine, clonidine, lisuride and iprazochrome have no significant influence on retinal spreading depression.

Acetaminophen↗

PubMed1996

[Behm's T-piece for reducing anesthesia gas pollution at the anesthesia work site].

The safety standards demanded for performing anaesthesia and the increasing burden of work to be handled by OP personnel entail continuous supervision and elimination of hazards and leaks. One example illustrates this necessity: Anaesthetic agents in the circular system of the induction are pollute the atmosphere after disconnection of one patient and transport into the OP suite and are a potential risk to personnel and next patient. C. Behm developed a T-piece which connects the Y-piece with the scavenging system leading to elimination of residual anaesthetics from the circular system. A useful byproduct is the longer life of the galvanic O2 sensor.

Air Pollutants, Occupational↗