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Biomedical subjects

C G Honegger

Publications and source records attributed to C G Honegger.

At least 37 records · Page 2Linked to original sources

Influence of zinc, D-penicillamine and oxygen on poisoning with Amanita phalloides. Zinc accelerates liver regeneration and prevents the depletion of brain noradrenaline caused by the mushroom.

Pretreatment with zinc aspartate increased the survival rate of mice poisoned with a lyophilisate from the mushroom Amanita phalloides (APL). In the livers of the zinc-treated animals, confluent necrosis was cleared earlier. Zinc also prevented the reduction of brain noradrenaline caused by the mushroom as well as the rise of brain dopamine and brain weight. D-Penicillamine also protected against the lethal effects of APL. The survival afforded by zinc pretreatment was marginally ameliorated by additional oxygenation.

Amanita↗

The effect of age on the microheterogeneous pattern of human myelin basic protein.

Dry weight, total basic protein and myelin basic protein (MBP) in human corpus callosum tissue were found to be significantly reduced with age, confirming other reports. The heterogeneous patterns of the MBP samples were investigated and could be classified into three groups: a normal one with peak 1 larger than peak 3; an old-age pattern with peak 1 smaller than peak 3; and a pathological pattern with peak 1 greatly reduced. Because peak 1 is the only one which is significantly reduced with age, it is suggested that future investigations could be simplified. The physiological and pathophysiological role of MBP heterogeneity is discussed.

Adult↗

Studies on neurotransmitter binding in senile dementia. Comparison of Alzheimer's and mixed vascular-Alzheimer's dementias.

Binding of 3H-labeled agonists and antagonists to muscarinic-cholinergic, alpha- and beta-adrenergic, dopaminergic, serotoninergic, and opiate receptors was studied in four regions of the neocortex and in hippocampus, thalamus, putamen, and caudatus in autoptic material from patients with senile dementia of Alzheimer type and of mixed vascular-Alzheimer pathogenesis. Different patterns of changes in ligand binding were found for the two groups. Some of these changes were quantitatively correlated with the histological scores of plaques and neurofibrillary tangles.

Aged↗

The effects of human myelin basic protein (HMBP) on the bioelectrical activity of the frog spinal cord.

The effects of human myelin basic protein (HMBP) and its individual microheterogeneous components on the electrical activity of the frog spinal cord are compared with those of bovine MBP (BMBP) and glutamate (Glu). HMBP causes a dose-dependent depolarization of the ventral (VR) and dorsal (DR) roots with a reduction of the evoked root potentials. The amplitude of the depolarization induced by 0.01 mM HMBP corresponds to that observed with application of 1 mM Glu. A weaker depolarization persists during blockade of synaptic transmission by MgSO4 or tetrodotoxin, suggesting a direct depolarizing effect on motoneurones and primary afferents. HMBP causes a long-lasting tachyphylaxis. The individual microheterogeneous components of HMBP (peaks 1, 2 and 3), and a mixture of smaller myelin basic proteins elicit similar responses, whereas BMBP and its microheterogeneous components are slightly less active.

Animals↗

Influence of early phases of paralysis on microcirculation of rat skeletal muscle.

By combining tissue pO2 measurements with morphological visualization and counting of perfused capillaries, early microvascular changes were investigated in paralysis of skeletal muscle of the rat. The models included experimental allergic encephalomyelitis (EAE), experimental allergic neuritis (EAN), 6-aminonicotinamide intoxication, and peripheral denervation. The results showed that in all models tissue oxygenation was either normal or elevated. In most cases this was accompanied by a reduced perfusion of the capillary bed, supporting the hypothesis of a dysfunction in oxidative metabolism. The effects of paralysis on capillary perfusion were more marked in red than in white muscles, except in spastic paresis. Flaccid paralysis had more deleterious effects on muscle microcirculation than spastic paralysis. Our data suggest that: (1) microvascular changes occur very early after the onset of paralysis and (2) later developing changes in the skeletal muscle such as atrophy cannot be ascribed to a lack of oxygen supply but rather, at least in part, to a dysfunction in oxidative metabolism.

6-Aminonicotinamide↗

Similar kinetic characteristics of 5-hydroxytryptamine binding in blood platelets and brain membranes of rats.

Blood platelets and brain membranes of SIV and Lewis rats both exhibited two saturable binding sites for 5-hydroxytryptamine (5-HT) in the concentration range 1-100 nM. The Kd values for the high-affinity sites were 4-6 nM and for the low-affinity sites 20-40 nM in both tissues of both rat strains. Blood platelets had 100-200 times more binding sites per mg protein (Bmax) than brain membranes. Thus, 5-HT receptors of platelets may be used as models for those of cerebral 5-HT-neurons.

Animals↗

Shape change of blood platelets induced by myelin basic protein.

Myelin basic protein (MBP) isolated from bovine spinal cord caused a marked shape change reaction of human blood platelets which was not accompanied by the release reaction and not inhibited by methysergide and spiroperidol. Only those basic proteins, including MBP, which had previously shown to exert neuronal depolarisation also induced the shape change reactions. Therefore, these findings may extend the use of platelets as neuronal models.

Animals↗

Shape change of blood platelets brought about by myelin basic protein and other basic polypeptides.

Basic proteins and polypeptides (BPP) such as myelin basic protein (MBP), polyornithine (M.W. 40,000), polylysine and protamine, which are known to cause neuronal depolarization in the central nervous system, induced a shape change reaction in blood platelets of various species, including man. This reaction was not accompanied by platelet aggregation or marked alterations of 5-hydroxytryptamine release. Cyclic nucleotide levels were also unchanged. The shape change induced by polyornithine was inhibited by heparin but not by antagonists of 5HT, catecholamines or gamma-aminobutryic acid, substances which are known to have no effect on the MBP-induced neuronal depolarization. Other basic substances, e.g. low molecular weight polyornithine (M.W. 4,000), cytochrome c, spermine and spermidine, did not induce either platelet shape change or (as shown before) neuronal depolarization. It is concluded, that 1) the shape change reaction of platelets seems to be a sensitive and simple means of detecting those BPP which induce functional changes in mammalian cells and 2) the use of platelets as models for neurons can be extended to include the action of BPP on the plasma membranes.

Animals↗

Myelin basic protein depolarizes neuronal membranes.

Bath application of 10(-5) M myelin basic protein (MBP) to various types of cultured nerve cells resulted in a membrane depolarization amounting to a change of 41 +/- 15 mV. Excitability could be restored by repolarizing the membrane by means of current injection through the recording electrode. The action of MBP persisted in the presence of tetrodotoxin (TTX), Co2+ or D-600 as well as in low Na+ and low Cl- solutions, whereas it was abolished by increasing extracellular Ca2+ concentrations. The action MBP was mimicked by ouabain. We propose that the effect of the protein might be generated by blockade of an ion pump. It is speculated that MBP may exert a direct effect on neuronal membranes in demyelinating diseases.

Animals↗

Studies on the action of myelin basic protein (MBP) in rat brain.

The specificity of I125-MBP uptake and subcellular distribution on a discontinuous sucrose density gradient, compared to those of histone H 4 and cytochrome c, showed a high affinity of MBP for mitochondria and heavy synaptosomes, and of histone H 4 for lighter synaptosomes. One heavier synaptosomal subpopulation was almost equally labelled by both proteins. Cytochrome c showed only a low uptake into particular material. Receptor interaction studies of MBP with H3-labelled 5-hydroxytryptamine and naloxone gave negative results.

Animals↗

Effect of multiple sclerosis serum on ventral root responses in isolated frog spinal cord.

Serum from patients with multiple sclerosis (MS) and other diseases was added to the medium perfusing isolated hemisected frog spinal cord, and the effect on ventral root responses (VRR) tested. As control, a standardized commercial human serum (Moni-trol I) was used. In 25 out of 40 spinal cord preparations Moni-trol gave inhibition of VRR ranging from 2.8 to 23.1%. 76% of the tests with confirmed MS sera showed inhibition of VRR, after deduction of the control serum effect, while 53% of the tests with sera from other diseases were inhibitory. Sera from cases of suspected but clinically unconfirmed MS gave strong inhibition (above 20%).

Animals↗

Transport kinetics for the uptake of (3H)glycine and (3H)L-glutamate into dorsal and ventral slices of rat spinal cord.

The uptake of [3H]glycine and [3H]L-glutamate into slices of the dorsal and ventral halves of rat spinal cord taken from the thoracal (T3-9) and lumbar (L1-6) regions was determined in the concentration range 2 - 1 000muM. For both amino acids and in all four tissue pieces (thoracal dorsal and ventral, lumbar dorsal and ventral) biphasic linear regressions were obtained from the Lineweaver-Burk plots, demonstrating saturable transport mechanisms both in the high-affinity and in the low-affinity range. No significant dorsal-ventral or lumbar-thoracal differences were found for the transport constants Km of both amino acids. For the maximum velocity V similar dorsal-ventral and lumbar-thoracal gradients were found for both glycine and L-glutamate. These results, which are not entirely in agreement with the distribution of the endogenous pools of these amino acids, are critically discussed in view of the proposed function of high affinity uptake at the synapse.

Animals↗

Partial separation of synaptosomes accumulating 4-aminobutyrate or glutamate by zonal centrifugation on a discontinuous sucrose gradient.

Rat cerebral cortex slices were incubated with 1muM [3H]4-aminobutyrate or [3H]L-glutamine. The subcellular distribution of the accumulated labelled substances were determined by fractionating the nuclei-free homogenates on a 5-step discontinuous sucrose density gradient in a B XIV zonal rotor. The gradient was designed to separate the synaptosomes into 3 subpopulations of increasing density. The patterns of distribution of [3H]4-aminobutyrate and [3H-a1L-glutamate in the three synaptosomal peaks were distinctly different. This indicates the presence of separate types of nerve ending accumulating these two potential neurotransmitters, which are known to be metabolically closely linked through the enzyme glutamate decarboxylase. Recentrifugation of the 3 synaptosomal peaks on flat step gradients in a swingout rotor did not result in any further enrichment in transmitter-specific synaptosomes.

Aminobutyrates↗