Biomedical subjects

M Schäfer

Publications and source records attributed to M Schäfer.

At least 19 recordsLinked to original sources

PubMed1992

Insulin-specific sensitization of cultured cerebrocortical neurons to glutamate excitotoxicity.

The effect of insulin on the sensitivity of neurons to excitatory amino acid-induced cytotoxic cell death was examined in primary cultures of the rat cerebral cortex. Cells developed for two weeks in serum supplemented medium in the presence or absence of insulin, insulin-like growth factor or b-fibroblast growth factor. Excitotoxic cell death was induced by 1 mmol/l glutamate, N-methyl-D-aspartate, kainate or quisqualate. The vulnerability of cells was evaluated by the measurement of lactate dehydrogenase release due to cytotoxic injury. In contrast to the moderate evaluation of protein content by all the 3 growth factors, only insulin increased the vulnerability of cells to the neurotoxic effects of glutamate and of the 3 excitatory amino acid receptor agonists examined. Our results show that the induction of vulnerability in cortical cultures is a specific action of insulin and not a general effect of growth factors. Moreover, the increased vulnerability to N-methyl-D-aspartate, quisqualate and kainate suggests that the effect of insulin is exerted through intracellular mechanisms other than a selective induction of one subpopulation of excitatory amino acid receptors.

Animals↗

PubMed1992

Setting complex tasks to single units in the avian auditory forebrain. II. Do we really need natural stimuli to describe neuronal response characteristics?

The response characteristic of auditory forebrain neurons in the European starling was established both with artificial stimuli (AS) and a conspecific territorial song as a natural stimulus (NS1). Applying experimenter-centred statistical methods for response detection and for scaling response strength, and spike-triggered analyses for the delimitation of the key sound parameters (spectrotemporal receptive field STRF, Aertsen et al. 1980) the study aimed at disclosing differences in the processing of the two stimulus classes, AS and NS. With the STRF as reference, we find congruence (1) in the best frequency with those determined under sweep and bandpass noise stimulation, (2) in response latency, and (3) in response-intensity dependence, further similarity in the overall frequency characteristic. Partitioning the song into 42 acoustically defined segments allowed to further delimit the response criteria under natural stimulation. They are easily understood from the AS response characteristics: (1) In the neuronal sample as a whole, long segments are more effective than short and, among the short, loud segments are more effective than faint; (2) Units showing their best excitatory response to AS in a certain frequency band are most probably excited by segments with a high proportion of their power concentrated upon or near this band; (3) Units with a slow (build-up) AS response react to a lower number of song segments than those dynamically following AS transients. Our data give no hint towards adaptive, feature detection properties of single neurons in field L. Instead, these neurons appear to base their response solely on the short-time spectrotemporal structure of the stimulus, irrespective of its natural or artificial origin.

Acoustic Stimulation↗

PubMed1992

[Percutaneous sonographic angioplasty. Initial experimental results].

Aim of the present study was to examine in vitro the effects of a new ultrasound catheter system on atherosclerotic and normal vessels before employing the system in humans. 141 attempts were made on 32 vascular preparations obtained at autopsy. The vessels were opened longitudinally within 24 hours of death, dilated with gelatine and were then "treated" in a waterbath using varying degrees of pressure, angle of incidence, sound intensity and duration of sound. Macroscopic and histological examinations of the preparation showed no morphological change in normal vessels except evidence of pressure by the catheter. In particular, there were no perforations of the vessel wall. In atherosclerotic segments there was significant reduction in the size of plaques following treatment.

Angioplasty, Balloon↗

PubMed1992

Heparin-associated thrombocytopenia in a patient treated with polysulphated chondroitin sulphate: evidence for immunological crossreactivity between heparin and polysulphated glycosaminoglycan.

Heparin-associated thrombocytopenia (HAT) type II, a severe side effect of heparin therapy, is thought to be induced by an immunological mechanism. By crossreactivity studies we have demonstrated that sera of patients with HAT type II activate platelets in vitro not only after the addition of heparin but also after addition of a chemically polysulphated chondroitin-like substance, Arteparon, used for treatment of degenerative joint disease. In addition here, we describe a patient who developed deep venous thrombosis and pulmonary embolism following administration of Arteparon and typical HAT type II with thrombocytopenia, 36 h after the first administration of heparin. This patient had never received heparin, but had repeatedly been treated with Arteparon for degenerative joint disease. We conclude that this patient had been presensitized by Arteparon, as indicated by his clinical course. In vitro studies again confirm crossreactivity between heparin and Arteparon.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1992

[The effect of muscle relaxants on masseter tone. An experimental study in an MH-susceptible swine model].

Malignant hyperthermia (MH) may occur, when a genetically predisposed individual or pig (MHS) is exposed to triggering agents. The increase in free, ionized sarcoplasmic calcium inducing the vicious circle of MH is believed to result from calcium-induced release with volatile anaesthetics, and from depolarization-induced calcium release with succinylcholine (SCH). The administration of SCH to susceptible humans or pigs frequently produces an increase in masticatory muscle tone. This hitherto ill-defined phenomenon is referred to as "masseter spasm" (MS). We have attempted to elucidate the pathophysiology of MS in a porcine model. METHODS. After the protocol had been approved by the state authorities, 6 MHS pigs were investigated. The pigs were mixed breeds (German Landrace and Dutch Pietrain) and were 9 +/- 1 weeks old with an average body weight of 25.5 kg. Premedication consisted of intramuscular injection of azaperone, 7.5 mg.kg-1. Anaesthesia was induced with piritramide, 1.2 mg.kg-1, administered via a cannulated ear vein. Subsequent to laryngoscopic endotracheal intubation, neuromuscular blockade was achieved with 4 mg pancuronium. Ventilation was set at 12 breaths per minute and adjusted to maintain an end-tidal CO2 concentration of 4.7% by adapting the tidal volume (PhysioFlex). Anaesthesia was maintained with piritramide, 2.25 mg.kg-1.h-1, pancuronium, 0.4 mg.kg-1.h-1, and N2O (60% in O2). Instrumentation included an arterial line, a central venous line, and a fiberoptic pulmonary artery catheter (Oximetrix). Masticatory muscle tone (MMT) was assessed with an intermolar balloon, connected to a pressure transducer and calibrated to zero prior to SCH administration. As a reference variable for effects produced by SCH, intraocular pressure (IOP) was measured manometrically in the anterior chamber. After stabilization of haemodynamic variables, the neuromuscular blockade was allowed to wear off. After recovery of the evoked masseter electromyogram, a paralyzing dose of pancuronium was administered (0.5 mg.kg-1). When paralysis was complete, SCH was administered (1.5 mg.kg-1), followed a few minutes later by dantrolene infusion (5 mg.kg-1 over 10 min). RESULTS. The administration of SCH was followed by clinically unequivocal MH episodes in all pigs, indicated by an increase in oxygen uptake (VO2; PhysioFlex; Fig. 1) and end-tidal CO2 concentration and a decrease in oxygen saturation of mixed venous blood (svO2; Fig. 2). Despite complete neuromuscular blockade (monitored with EMG), SCH produced an increase in MMT in all pigs which was reversed by dantrolene (Fig. 3). The time course of MMT paralleled that of IOP, suggesting a similar underlying mechanism. DISCUSSION. Succinylcholine is a trigger of MH in susceptible individuals; onset of the syndrome may be associated with "masseter spasm". SCH increases extraocular muscle tone, probably by means of stimulating multiply innervated fibers; the resulting IOP increase is not prevented by competitive neuromuscular blockade. The existence of multiple innervated fibers has also been shown in muscle spindles in the deep layers of the masseter, with their stimulation resulting in elevation of the jaw. We speculate that the increases in MMT and IOP observed in this study reflect the same process, i.e. a motor response, initiated by SCH-induced stimulation of the intramyocellular contractile system of multiply innervated muscle fibers, that is independent of neuromuscular transmission. Triggering of MH with SCH despite complete neuromuscular blockage suggests a mechanism other than depolarization-induced calcium increase. And, for the semantics, according to neurological terminology MS should be referred to as contracture not as spasm.

Anesthesia, Inhalation↗

PubMed1992

[A fatal intraoperative cerebral ischemia following kinking of the internal carotid artery?].

Postoperative neurological deficit may result from ischaemic or hypoxic hypoxaemia. Postural cerebral hypoperfusion may ensue when a pre-existing asymptomatic vascular anomaly in combination with rotation of the head for surgical positioning compromises cerebral blood flow. CASE REPORT. A 30-year-old man was referred for recraniotomy for glioblastoma. Following uneventful induction of anaesthesia, increased diuresis and progressive hypothermia were observed. The postoperative period was complicated by a seizure, followed by apnoea requiring reintubation of the trachea. A CAT scan revealed global cerebral oedema with subtotal compression of the third ventricle. Intracranial pressure was 60 mm Hg as measured by an epidural probe. On the 1st postoperative day clinical and electroneurophysical signs of brain death were observed; the patient underwent organ explantation the next day. PATHOLOGY. Pathological examination revealed pronounced global hypoxaemic lesions and an S-shaped internal carotid artery with intimal proliferation (Fig. 1). The diagnostic conclusion was cerebral ischaemia following carotid occlusion caused by carotid kinking and completed by surgical positioning (rotation of the head). CONCLUSION. Carotid kinking is a rare abnormality, and patients at risk may not be identified preoperatively. Though it is questionable whether this disaster could have been prevented at all, electroneurophysiological monitoring would have been the only early monitoring system capable of detecting diminishing cerebral blood flow. Although a request for routine intraoperative neurophysiological monitoring seems unrealistic at present, it has to be acknowledged that only such monitoring could have provided the information needed to save this patient.

Adult↗

PubMed1992

[Clinical forms of enzootic pneumonia in calves and their effects on respiration].

Enzootic pneumonia was diagnosed in 160 of 225 bullocks in a livestock fattening unit. Within the first 10 weeks, 51 of those affected contracted the disease a second time after the symptoms had vanished. Acute catarrhal bronchopneumonia were most common (49.3%) during the first outbreak, whereas acute catarrhal purulent bronchopneumonia (39.2%) and chronic pneumonia (29.4%) were most common during the second. Arterial blood gas analysis was undertaken for 33 clinically healthy bullocks and 100 bullocks with clinically diagnosed acute bronchitis, acute catarrhal bronchopneumonia, acute catarrhal purulent bronchopneumonia and chronic pneumonia. The pO2, SATO2 and A-aDO2 levels found in blood from the abdominal aorta of all diseased animals differed significantly from those of healthy animals. The values for animals with distinct catarrhal bronchopneumonia and catarrhal purulent bronchopneumonia showed the greatest differences.

Animals↗

PubMed1991

Development of glutamate neurotoxicity in cortical cultures: induction of vulnerability by insulin.

The effect of insulin on the development of excitotoxic vulnerability in primary cultures of the rat cerebral cortex was examined. Cells were maintained for two weeks in serum-supplemented culture media, in the presence or absence of increasing insulin concentrations. Excitotoxic cell death was induced by 1 mM glutamate. The vulnerability of cells was evaluated by phase contrast microscopy and by the measurement of lactate dehydrogenase (LDH) release due to cytotoxic injury. In addition to a moderate (less than 50%) stimulation of protein and DNA synthesis, insulin produced more than a twofold increase in the excitotoxic vulnerability of cells. The effect of insulin was specific, concentration-dependent and required an intact molecular structure of insulin. Our findings indicate that insulin induces significant changes in cerebral neurons by increasing the lethal vulnerability of cortical cells to excitatory amino acids (EAAs).

Animals↗

PubMed1991

Memantine is highly potent in protecting cortical cultures against excitotoxic cell death evoked by glutamate and N-methyl-D-aspartate.

The capacity of memantine to protect cultured cerebrocortical cells against N-methyl-D-aspartate (NMDA)- and glutamate-induced cell death was examined. Excitotoxic cell death was evaluated by phase contrast microscopy and quantified by estimating the release of lactic dehydrogenase from damaged cells. Memantine showed a strong, long-lasting and concentration-dependent protective effect against the excitotoxic damage induced by glutamate and NMDA, with almost complete protection being attained at a memantine concentration of 0.1 mM. The present findings indicate that memantine has potential value as a drug against excitotoxic brain damage.

Animals↗

PubMed1991

A cluster of four genes selectively expressed in the male germ line of Drosophila melanogaster.

The gene Mst87F is exclusively expressed in the male germ line and is subject to translational regulation. The Mst87F mRNA is transcribed in the primary spermatocytes, stored for three days and then subsequently translated in the post-elongation period of spermiogenesis. Here we report on the isolation of a cluster of four small genes closely related in structure and function to Mst87F. These genes are located at polytene band 84D on the right arm of chromosome three and are named Mst84Da, Mst84Db, Mst84Dc and Mst84Dd. All four genes encode putative proteins composed primarily of a repetitive motif of cysteine-glycine-proline. The genes are exclusively expressed in the male germ line. The poly(A) tail of the Mst84D mRNAs increases in length at day three of pupal development, the time at which a similar change in Mst87F mRNA and translation has been shown to begin. In addition we have identified a conserved 12 base pair element within the 5' untranslated region (UTR) of each gene which is also found at an identical position in Mst87F and which has been demonstrated to be the structural element for translational control of Mst87F expression (Schäfer et al., 1990 EMBO J. 9, 4519-4525). We have mapped the gene cluster to a small deletion associated with a rotund mutation at 84D. Although flies with a homozygous deletion of the cluster still produce motile sperm, electron microscopic examination revealed numerous malformations in the ultrastructure of the axoneme resulting in a drastic reduction of motile sperm.

Amino Acid Sequence↗

PubMed1990

Trial of iloprost versus aspirin treatment for critical limb ischaemia of thromboangiitis obliterans. The TAO Study.

152 patients with thromboangiitis obliterans (Buerger's disease) and pain from critical leg ischaemia were randomly allocated to receive iloprost, a chemically stable prostacyclin analogue, or low-dose aspirin, for 28 days in a double-blind trial. On review, 19 patients did not fulfil the stringent entry criteria. Of the other 133 patients, 98 also had leg ulcers. After 21-28 days, 58 (85%) of 68 iloprost-treated patients showed ulcer healing or relief of ischaemic pain, compared with 11 (17%) of 65 in the aspirin-treated group. 43 (63%) on iloprost treatment had complete relief of pain, compared with 18 (28%) on aspirin. Ulcers healed completely in 18 of 52 (35%) who received iloprost compared with 6 of 46 (13%) who received aspirin. 6 months after the start of treatment, the response rate was 45 of 51 (88%) patients treated with iloprost compared with 12 of 44 (21%) patients treated with aspirin.

Adolescent↗

PubMed1990

A conserved element in the leader mediates post-meiotic translation as well as cytoplasmic polyadenylation of a Drosophila spermatocyte mRNA.

We have previously shown that Mst87F (previously called mst(3)g1-9), a gene which is exclusively expressed in the male germ line of Drosophila melanogaster, is subject to negative translational control. While transcription of this gene takes place premeiotically, translation occurs only after the elongation of spermatids is complete. We report here the identification of a sequence element within the first 45 nucleotides of the leader which is crucial for this translational regulation. Sequence comparison with six other genes, which form a gene family with Mst87F, shows the conservation of a twelve nucleotide element within this leader segment. It is found in all genes at positions +28 to +39 of the leader. Deletion of this element or alteration of two nucleotides by in vitro mutagenesis both lead to the breakdown of the translational control mechanism. The poly(A) tail of the Mst87F mRNA becomes longer and heterogeneous in length when the mRNA is recruited for translation. We present evidence that the control for this additional polyadenylation also resides within the conserved element of the leader.

Animals↗

PubMed1990

Ontogenesis of auditory fovea representation in the inferior colliculus of the Sri Lankan rufous horseshoe bat, Rhinolophus rouxi.

This report describes the ontogenesis of tonotopy in the inferior colliculus (IC) of the rufous horseshoe bat (Rhinolophus rouxi). Horseshoe bats are deaf at birth, but consistent tonotopy with a low-to-high frequency gradient from dorsolateral to ventromedial develops from the 2nd up to the 5th week. The representation of the auditory fovea is established in ventro-medio-caudal parts of the IC during the 3rd postnatal week (Fig. 3). Then, a narrow frequency band 5 kHz in width, comprising 16% of the bat's auditory range, captures 50-60 vol% of the IC (Fig. 3c). However, foveal tuning is 10-12 kHz (1/3 octave) lower than in adults; foveal tuning in females (65-68 kHz) is 2-3 kHz higher than in males (62-65 Khz). Thereafter, foveal tuning increases by 1-1.5 kHz per day up to the 5th postnatal week, when the adult hearing range is established (Figs. 4, 5). The increase of sensitivity and of tuning sharpness of single units also follows a low-to-high frequency gradient (Fig. 6). Throughout this development the foveal tuning matches the second harmonic of the echolocation pulses vocalised by these young bats. The results confirm the hypothesis of developmental shifts in the frequency-place code for the foveal high frequency representation in the IC.

Acoustic Stimulation↗

PubMed1990

Audiovocal interactions during development? Vocalisation in deafened young horseshoe bats vs. audition in vocalisation-impaired bats.

Horseshoe bats (Rhinolophus rouxi) were deafened in their 3rd-5th postnatal week. Subsequently their vocalisations were monitored to evaluate the impact of audition on the development of echolocation pulses. Hearing impairment affected the echolocation pulses as follows: the frequency of the constant frequency (CF) component was altered by between +4 kHz and -14 kHz, and the dominance of the second harmonic of the pulses was neutralised by a relative increase in intensity of the first and third harmonics. A second experiment focused on possible influences of acoustical self-stimulation with echolocation pulses on the establishment of auditory fovea representation in the inferior colliculus (IC). Frequency control of echolocation pulses was disrupted by larynx denervation. Thereafter, the bats produced multiharmonic echolocation signals (4-11 harmonics) varying in frequency. IC tonotopy, however, as monitored by stereotaxic electrophysiology, showed the same developmental dynamics as seen in control specimens (Fig. 10). Both experiments indicate that throughout postnatal development echolocation pulses are under auditory feedback control, whereas maturation of the auditory fovea and shifts in its frequency tuning represent an innate process. The significance of this postnatal development might be the adjustment of the vocal motor system of each bat to the frequency of its 'personal' auditory fovea.

Animals↗

PubMed1990

[Subacute butyric acid exposure in cattle. 4. Clinical influence and effect on the carbohydrate-fat metabolism and liver function of cows].

Eleven cows in late lactation were exposed to butyric acid for three weeks and were compared to five controls. Two intraruminal doses were daily applied, that is 1.0 g/kg B.W. of butyric acid to six animals and 1.0 g/kg B.W. of sodium butyrate to another five. Decline in milk yield was clinically recorded in response to butyric acid, while muscle tremor and diarrhoea resulted additionally from sodium butyrate. Behaviours of the clinico-chemical parameters of beta-OH-butyrate, glucose, free fatty acids, bilirubin, ASAT, gamma-GT, AP, and cholesterol were comparable to those in fattening bulls. Liver damage was not safely established. Some of the clinico-chemical alterations were more strongly pronounced after administration of sodium butyrate. One cow fell ill with ketosis under butyric acid load.

Animals↗

PubMed1990

[Subacute butyric acid exposure in cattle. 5. Effect on the acid-base equilibrium and protein metabolism in cows].

Acid-base balanced in cows were but slightly affected by butyric acid exposure experiment over three weeks. Applications of sodium butyrate over the same period of time, on the other hand, was associated with buildup of alkalosis in the second half of the experimental period, with alternation of loading, compensation, and reloading being recordable. Nitrogen metabolism in cows was but slightly affected under the given experimental conditions. However, clearly noticeable impairment of nitrogen metabolism was exhibited by one cow that had fallen ill, in the course of experimentation.

Acid-Base Equilibrium↗

PubMed1990

[Relationship between metabolic status and results of embryo collection in high-producing cows].

Blood samples were taken from 58 high-performance cows earmarked as donors for embryo transfer, one day before artificial insemination and following superovulation. An evaluation of 16 major indices showed the yield of transferable embryos to be clearly reduced by hypocholesterolemia, hyperproteinemia, and even more by hypophosphatemia. More than one deviating metabolic findings were obtained only from few animals which had the desired high number of embryos, that is above seven.

Animals↗

PubMed1990

[Status of plasmapheresis and cyclosporin A in the treatment of systemic lupus erythematosus].

We report the history of 2 teenagers suffering from systemic lupus erythematosus for more than 5 years. Both of them were treated with total plasma exchange (TPE) and Ciclosporin A. They responded well to this therapy and achieved remissions. Especially the 2nd patient showed a dramatic clinical improvement after a relapse caused by sun exposure. Both treatment modalities are discussed and the following conclusions are drawn: TPE is an important therapeutic element in treating patients with SLE, whereas Ciclosporin A is not recommended for therapy of first choice. Further prospective and controlled studies have to show, if there is a benefit of this therapy, especially in childhood.

Adolescent↗