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Biomedical subjects

U Meyer

Publications and source records attributed to U Meyer.

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

Temperature compensation of the circadian period length--a special case among general homeostatic mechanisms of gene expression?

In Neurospora crassa, as well as in other organisms, the expression of housekeeping genes is transiently suppressed after exposure to higher temperatures (30-45 degrees C); expression is then reactivated and adapts after a few-hours to values closer to the initial rates. Adaptive mechanisms apparently exist in the processes of transcription, RNA processing, and translation and render protein synthesis rates temperature compensated. Heat shock proteins (HSPs) play an important role within these mechanisms ("acquired thermotolerance of protein synthesis"), but their function is as yet not exactly known. Adaptive mechanisms seem also to involve intracellular ion changes after exposure to moderate temperature elevation. The expression of heat shock genes is transiently enhanced after exposure to higher temperatures and also adapts after a few hours. The adaptation mechanism includes inactivation of the heat shock transcription factor (HSF) by means of phosphorylation changes and possibly by binding of a gene product (HSP70)-a mechanism representing a negative feedback control. These examples demonstrate the existence of general adaptive mechanisms at different levels of gene expression that may also be at work in the temperature compensation of clock gene expression. Apart from such adaptation processes, antagonistic reactions within the processes of gene expression and protein modification might be equally enhanced or suppressed by temperature changes, leaving the equilibrium unaffected or balanced (antagonistic balance, see Ruoff et al., this issue of Chronobiology International). This principle is shown to apply to the effect of temperature elevation on total protein synthesis and degradation. It may also apply to other antagonistic processes such as phosphorylation-dephosphorylation or monomer-dimer formation. The circadian clock mechanism is assumed to consist of several processes that can either adapt or produce a balance. Single amino acid changes in a clock protein are assumed to partially upset this adaptation or balance.

Circadian Rhythm↗
PubMed1997

No mechanical role for vinculin in strain transduction in primary bovine osteoblasts.

Vinculin is thought to play a central role in linking the actin cytoskeleton to the integrin adhesion proteins of focal contacts and also in cell-cell adhesion sites. We have investigated aspects of attachment and the transduction of mechanical stimulation on the function of vinculin and its assembly in primary bovine osteoblasts. The dynamic attachment process was concomitant with the reassembly of vinculin from a soluble cytoplasmic pool into Triton-insoluble focal adhesions. Immunoblotting experiments demonstrated a slight increase in the amount of vinculin concentrated in focal contacts that was paralleled by a discrete decrease in the Triton-soluble fraction of cytoplasmic vinculin. Sixty cycles of 1 Hz deformations at 0.02% (hypophysiological, no change in cell division rate), 0.2% (within the normal physiological range), and 1% (hyperphysiological) resulted in a rapid and reversible disassembly of vinculin from focal contacts to a homogeneous cytoplasmic localization, although alterations in the shape and morphology of cells could not be detected. Although all mechanical loading protocols dramatically depleted vinculin from focal contacts, its initial distribution in adhesion plaques was fully restored within the next 60 min, demonstrating the highly dynamic and reversible shift of this protein from a membrane-associated pool to the cytoplasm. By first depleting vinculin from the focal adhesion sites by applying 0.02% strain, waiting 60 s, and then applying 0.2% strain, we show that the transduction of mechanical deformation was identical with controls that had not been pretreated. This indicates that vinculin does not play a role in mechanical transduction, that significant mechanical forces are not transmitted through vinculin, and also that loss of vinculin at the focal adhesion site does not have significant effects, in the short term, on cell adhesion.

Animals↗
PubMed1996

Effect of organic nitrates on ex vivo platelet aggregation and fibrinolysis in man.

Previous in vitro studies have suggested that nitric oxide-releasing agents can increase the fibrinolytic capacity while platelet aggregability is decreased. We have therefore directly compared the influence of organic nitrates on ex vivo platelet aggregation and the fibrinolytic system in 16 healthy volunteers. Each subject received glyceryl trinitrate (GTN, 2 x 32 mg patches), isosorbide-dinitrate (ISDN, 120 mg p.o.), isosorbide-5-mononitrate (ISMN, 50 mg p.o.), and placebo in a randomized double-blind manner. Ex vivo platelet aggregation, activities and concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured before, 90 and 150 minutes after drug intake. GTN, ISDN, and ISMN were equipotent in respect to their hemodynamic responses. Platelet aggregation induced with a low (1 microM) but not with a high (4 microM) agonist concentration (adenosine diphosphate, ADP) was reduced after GTN and ISDN. ISMN had no influence on aggregation. An increase of t-PA activity was significantly reduced after GTN and ISDN (p<0.05), whereas t-PA concentrations were not affected by the nitrates. A decrease of PAI-1 activity after ISMN and placebo was not apparent after GTN and ISDN. In the case of GTN, the decrease of PAI-1 concentration was delayed. In conclusion, GTN and ISDN did not increase the fibrinolytic capacity but decreased the reversible phase of ADP-induced platelet aggregation, while ISMN had neither an effect on the fibrinolytic system nor on platelet aggregation.

Adenosine Diphosphate↗
PubMed1996

"IR-Spectroscopy" - computer-program for the interpretation of infrared spectra.

A computer-program "IR-Spectroscopy" for the interpretation of infrared spectra of organic compounds is described. It contains the following basic items for preprocessing and execution of the computer based interpretation process: handling of the rule-base CorTab, routines for automatic rule generation and interpretation modules on the basis of the programming languages PROLOG and C.

Journal Article↗
PubMed1996

Morphometrical investigations on lamina-V-pyramidal-neurons in the frontal cortex of a case with anorexia nervosa.

Pyramidal neurons in the motor cortex of a lethal case of anorexia nervosa were investigated by means of a computer-assisted three-dimensional quantitative neuronographic method. The differentiation level of GOLGI-impregnated lamina-V/VI-pyramidal-neurons was analyzed by comparison of parameters such as the number of basal dendritic fields, ramification degree, length of dendritic segments and spine density with data estimated in another case of corresponding gender and age. In the anorexia case, as well as typical pyramids, a slim neuron type with one extremely long basal dendritic field was found to occur more frequently. In all the neurons investigated, the ramification pattern of single basal dendritic fields was found to be reduced and changes in the spine morphology as well as a reduction in spine density were observed. However, a simultaneous lengthening of the terminal dendrites of higher order give some evidence for the coincidence of regressive process with repair mechanisms and neuronal plasticity.

Adolescent↗
PubMed1995

The concept of "direct mechanical ventricular assistance" in the treatment of left-ventricular failure. Part 2. Results of the new intrathoracic implantable multi-chamber pump system (IMPS) in an animal study.

An assist device was developed which is able to support the pumping function of the heart by direct application of pressure to the left ventricle. The goal of this animal study in pigs was to determine whether it is possible to maintain sufficient blood circulation with the aid of the new system when the heart is fibrillating or its capacity has been greatly reduced. Following sternotomy complete invasive monitoring was installed. The intrathoracic implantable mechanical multi-chamber pump system (IMPS) was placed around the left ventricle. By means of the beta-blocker carazolol, systolic left-ventricular pressure (LVPsys), cardiac output, heart rate, and left-ventricular dp/dtmax (LVdp/dtmax) were gradually lowered and the pump system was tested intermittently. Then the heart was fibrillated and the system was tested again. When cardiac output, LVdp/dtmax, and systolic blood pressure were reduced by approximately 50% IMPS was able to increase LVPsys by 83% (IMPS) on: 96 +/- 9 mmHg vs. IMPS off: 63 +/- 6 mmHg), and the blood pressure in the carotid artery by 86% (IMPS on: 95/40 +/-15 mmHg vs. IMPS off: 69/38 +/- 9 mmHg). The mean cardiac output was 64% (IMPS on: 4.3 L/min vs. IMPS off: 3.9L/min); in most cases a great variability could be observed depending on the preload, the heart rate, and the mode of pressure application. When the heart was fibrillating, IMPS was able to maintain adequate circulatory conditions with LVPsys = 88%, blood pressure in the carotid artery = 85%, and LVdp/dtmax = 57% of the control values measured before fibrillation and beta-blockade. The system presented here is able to support the impaired left ventricle and to replace its pumping function. The advantages of the system are its efficiency and the lack of contact of the circulating blood with foreign surfaces. Whether the system is suited for bridging and recovery support shall be clarified in further studies.

Adrenergic beta-Antagonists↗
PubMed1995

The concept of "direct mechanical ventricular assistance" in the treatment of left-ventricular failure. Part 1: Idea, development and construction of an implantable multi-chamber pump system partially surrounding the heart.

In this paper we present a therapeutic concept for the treatment of heart failure due to muscular inability to pump properly. The basic principle of this concept triggered numerous studies, then with the aim of cardiopulmonary resuscitation, back in the 1970s. In general, it dealt with mechanical systems which led to an increase in stroke volume, systolic blood pressure, and cardiac output through the application of pressure directly to the left ventricle. After a critical appraisal of the relevant literature from technical, physical, and medical viewpoints, and our own preliminary studies on animal hearts within the framework of mock circulation experiments, we have conceived a new functional principle for direct mechanical ventricular assistance based on squeezing the left ventricle only. We have begun development of the system which has the advantages of ease of use, high biocompatibility due to lack of contact between blood and system components, the prevention of infection through complete intrathoracic implantation (long-range goal), and the fact that the patient's own heart can be supported by the system without being removed from the circulatory system (support of the residual myocardial function). Technical as well as medical prerequisites are indicated, and the materials selection and construction principles of the control, pressure generation, pressure transduction, and ventricular compression unit are described. It has proved possible to construct a prototype system to be used in animal experiments, which, through pneumatic inflation of a chamber system partially surrounding the left ventricle, should be able to augment or take over the pumping function of the left ventricle.

Animals↗
PubMed1995

Close Correlation between Heat Shock Response and Cytotoxicity in Neurospora crassa Treated with Aliphatic Alcohols and Phenols.

In Neurospora crassa the aliphatic alcohols methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutanol, ethylene glycol, glycerol, and allyl alcohol and the phenolic compounds phenol, hydroquinone, resorcinol, pyrogallol, phloroglucinol, sodium salicylate, and acetylsalicylic acid were analyzed with respect to their capacities to induce heat shock proteins (HSP) and to inhibit protein synthesis. Both the alcohols and phenols showed the greatest levels of HSP induction at concentrations which inhibited the overall protein synthesis by about 50%. The abilities of the different alcohols to induce the heat shock response are proportional to their lipophilicities: the lipophilic alcohol isobutanol is maximally inductive at about 0.6 M, whereas the least lipophilic alcohol, methanol, causes maximal induction at 5.7 M. The phenols, in general, show a higher capability to induce the heat shock response. The concentrations for maximal induction range between 25 mM (sodium salicylate) and 100 mM (resorcinol). Glycerol (4.1 M) shifted the concentration necessary for maximal HSP induction by hydroquinone from 50 to 200 mM. The results reveal that the induction of HSP occurs under conditions which considerably constrain cell metabolism. The heat shock response, therefore, does not represent a sensitive marker for toxicity tests but provides a good estimate for the extent of cell damage.

Journal Article↗
PubMed1994

[Mexiletine in treatment of painful diabetic neuropathy].

The objective of this double-blind placebo controlled multicenter study was to prove the efficacy of mexiletine in painful diabetic neuropathy. Treatment was provided for in three dosages. For pain measurements a visual analogue scale (VAS) and McGill's verbal rating scale were chosen. 95 patients were included. A global assessment of the VAS showed no differences in treatment. The total evaluation (PRIT = Pain Rating Index Total) of the McGill scale just failed the level of significance. More specific exploratory evaluation of subclasses of the McGill scale, representing different qualities of pain, gave remarkable differences between mexiletine and placebo. According to types of complaints an evaluation showed substantial advantages of the mexiletine treatment with both the VAS and the McGill scale. There is strong evidence that particularly patients with stabbing or burning pain, heat sensations or formication will benefit most by mexiletine therapy. Concerning the dosage, a medium regimen of 450 mg per day seems to be appropriate in this indication. With an increase in dosage the efficacy does not rise proportionally. Mexiletine proved a very safe therapy with negligible side effects at the medium dose range, even less than placebo. There were no cardiovascular side effects. Further investigations should pay more attention to the variety of the complaints and include the quality of life.

Adult↗
PubMed1994

Signal-averaged ECG in prediction of the short-term suppression of ventricular premature beats by Mexiletine.

We analyzed whether baseline parameters of time-domain and spectrotemporal analysis of a signal-averaged ECG or their changes during Mexiletine therapy can predict the antiarrhythmic efficacy of the drug. On 60 post-MI patients with > 100 ventricular premature beats per hour, signal-averaged ECGs were recorded before and after a constant infusion of Mexiletine (7 mg/kg) for 1 h and again after 4 days of oral Mexiletine therapy (Mexiletine SR, 360 mg twice daily). Spectrotemporal analysis was performed on a fixed analyzed signal duration of QRS-complex and ST-segment of X-, Y-, Z-leads using the temporal window of the rectangular type, measuring signals between 10-20 Hz. Intravenous and oral Mexiletine did not produce significant changes in mean values of any time-domain parameters. However, using informative variables of spectra of the signal-averaged ECG, we managed retrospectively to predict antiarrhythmic efficacy in 92% of the patients. Only certain frequency bands (from the range of the spectra at baseline, 10-120 Hz) were predictive for intravenous Mexiletine efficacy: 40-55 Hz in lead Y (P = 0.0116); 55-70 Hz in leads X and Z (P = 0.0063 and P = 0.0269, respectively); 70-85 Hz in lead Z, (P = 0.0227). When the treatment with intravenous Mexiletine was effective, the baseline power spectrum density was lower than when the drug was ineffective, and vice versa. Moreover, the efficacy of oral Mexiletine can be predicted by power density spectrum at baseline (10-25 Hz in lead Z, P = 0.0210; 70-85 Hz in lead Y, P = 0.0254) and by one of the possible (increased, decreased, unchanged) effects of intravenous Mexiletine on the spectra at frequency bands (70-85 Hz in lead X, P = 0.0432 and 40-120 Hz in lead Z, P = 0.0156). These results show the value of spectrotemporal signal-averaged ECG in selecting a subgroup of post-myocardial infarction patients that may benefit from Mexiletine therapy.

Administration, Oral↗
PubMed1994

[Adjuvant treatment with mitomycin eyedrops after pterygium excision: Ticino experience].

AIM OF THE STUDY: Prospective pilot-study in the canton of Ticino to evaluate the prevention of recurrence of pterygium after excision and mitomycin drops. METHODS: Mitomycin 0.02% drops have been used from 6 to 10 days after 24 cases of corneoscleral excision of the pterygium. RESULTS: After a mean observation time of 13 months, we did not see any recurrence. The vision was improved in 8 eyes over 21, was unchanged in 15 eyes and deteriorated in 1 eye due to unrelated causes. In two cases we observed a thinning of 0.3 mm deep over 1 mm2 of the sclera. CONCLUSIONS: The rate of recurrence after excision of the pterygium and followed by instillation of mitomycin drops is lower than the other described treatments. However, complications described in literature, yet not observed in our own study, underline the necessity of a prolonged perspective study.

Adult↗
PubMed1994

The effects of intravenous mexiletine on spectra of the signal-averaged ECG.

This study examined the effects of intravenous mexiletine on the time-domain and spectrotemporal signal-averaged ECG (SAECG). SAECGs were recorded in 60 postmyocardial infarction (MI) patients with more than 100 premature ventricular beats per hour, before and after a constant infusion of mexiletine, 7 mg/kg, given over 1 hour. Spectrotemporal analysis was done on a fixed analyzed signal duration of QRS complex and ST segment of X, Y, and Z leads using a temporal window of rectangular type, measuring the signal content between 10-120 Hz. Intravenous mexiletine produced no significant change in the mean values of any of the time-domain variables. However, mexiletine either increased or decreased the power density spectrum (PDS) and PDS ratio (40-120 Hz/25-120 Hz) of the SAECG, and in rare cases only did it not alter the spectra of the SAECG. When PDS ratio in lead Z decreased after mexiletine, it was usually higher at baseline in comparison with that when the PDS ratio increased, or vice versa. When the treatment with mexiletine was effective, PDS increased in comparison with that when the drug was ineffective, or vice versa. Not all ranges (10-120 Hz) of spectra of the SAECG, but only certain frequency bands (25-40 Hz in lead Z, P = 0.0253; 40-55 Hz in lead Y, P = 0.0096; 55-70 Hz in X lead, P = 0.0018; and in lead Z, P = 0.0002; 70-85 Hz in lead X, P = 0.0025; and in lead Z, P = 0.0075, 85-100 Hz in lead X, P = 0.0033) were associated with mexiletine efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiography↗
PubMed1993

Biological evaluation of an ionomeric bone cement by osteoblast cell culture methods.

Periosteal derived bovine osteoblast-like cells migrated in culture onto an ionomeric cement. Cell cultures were maintained for 4 weeks and used to study the in vitro behaviour of cells on the ionomeric bone cement (IC). The cells produced bone matrix proteins (osteocalcin, bone sialoprotein II) and were osteoblast-like. The osteoblast-like cells colonized the substrate in monolayers and produced an extracellular matrix as seen by light and scanning electron microscopy. Morphological comparison between cells growing on the ionomeric bone cement and cortical bone revealed no significant difference in phenotypic expression. Staining for aluminium in osteoblasts growing on the IC showed an uptake and storage of aluminium in the cells. Energy dispersive X-ray microanalysis revealed high concentrations of aluminium and silicon in the periosteal tissue. Despite the known toxic effect of aluminium in vivo and in vitro on osteoblasts, no signs of toxicity were apparent on light and scanning electron microscopy analysis.

Aluminum Oxide↗
PubMed1993

[Sleep apnea screening in a pulmonary-internal medicine rural practice in Mecklenburg-Vorpommern].

In a screening study of a total of 230 patients covered on the occasion of an x-ray mass screening (Group A: 157 patients) or within the framework of a pulmonology-cardiology-orientated medical consulting-room practice (Group B: 73 patients), 178 patients said "snoring" was their major symptom, whereas 35 patients considered "apnoea" to be the main complaint. Looking at both groups more closely and with greater differentiation we find in Group B a high incidence of the characteristic symptoms "snoring" and "apnoea" and a score of more than +2, compared with Group A, concomitant with a high coincidence of a positive finding in the MESAM study (Group A: ration 55.5:1, Group B: ratio 4.3:1). 18 patients were found to be suffering from sleep apnoea syndrome. Due to limited facilities we have so far been able to adjust only two of these patients to CPAP/BiPAP in the sleep laboratory of the Hospital for Pulmonological Diseases in Schwerin. We conclude that it seems problematic to conduct mass screening on a broad basis of the population (another argument being the cost/benefit ratio), whereas it appears to be more effective to conduct an on-target search for sleep apnoea syndrome (SAS) in high-risk groups. A prerequisite for appropriate coverage and treatment of sleep apnoea patients is to provide patients with on-target and wide-scope information on the disease pattern; furthermore, both doctors and the population must be provided with examination facilities also on an outpatient basis.

Adult↗
PubMed1992

Electrophysiological and morphological changes in rabbit retina after exposure to the light of the operating microscope.

Healthy adult rabbit eyes were exposed to up to 4 h of continuous illumination with moderate light intensity, as is produced by the lamp of an ophthalmic operating microscope. Electroretinograms were recorded before and after the long period of illumination. The depression of the waves in the electroretinograms observed just following light exposure recovered within 1 h to normal values. Electron microscopy of the retina revealed changes within the cells of the pigment epithelium. These results are discussed in view of their clinical implications in human patients.

Animals↗