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A Probst

Publications and source records attributed to A Probst.

At least 199 records · Page 11Linked to original sources
PubMed1986

Muscarinic cholinergic receptor subtypes in the human brain. II. Quantitative autoradiographic studies.

The distribution and characteristics of M1 and M2 muscarinic cholinergic receptors as defined by their affinity for the antagonist pirenzepine were studied in the human brain using in vitro quantitative autoradiographic techniques. The binding of N-[3H]methylscopolamine ([3H]NMS) to cortical and striatal microtome tissue sections was saturable and presented a Kd of 0.25 nM. The sensitivity of [3H]NMS-binding sites to 100 microM carbachol and 300 nM pirenzepine was analyzed in 30 brain areas. In selected brain regions, complete competition curves using carbachol, pirenzepine and atropine were analyzed. Finally, the regional distribution of M1 sites was studied using [3H]pirenzepine ([3H]PZ) as ligand. The binding of [3H]NMS to striatum, hippocampus and amygdala was very sensitive to pirenzepine but not to carbachol. The opposite situation was found in thalamus, hypothalamus, substantia innominata, pons and medulla, while intermediate sensitivity to both displacers was observed in different layers of the cortex and in the claustrum. Competition experiments showed that [3H]NMS binding was displaced with the same affinity by atropine in all the regions studied, while the IC50 of carbachol varied from 5 microM in the nucleus facialis to 830 microM in the caudate. Pirenzepine IC50 values for [3H]NMS sites varied from 66 nM to 1 microM. Results using [3H]PZ further confirm this pattern of distribution, with high densities of binding observed in the striatum, hippocampus and amygdala and very low in thalamic and brainstem areas. These results show that the putative M1 and M2 muscarinic receptor subtypes present a differential anatomical distribution in the human brain. This differential distribution is comparable to that observed in the rat brain. Some basal ganglia and limbic areas are enriched in M1 sites, while thalamus, brainstem, medulla and also the hypothalamus and substantia innominata contain predominantly receptors of the M2 type. The cerebral cortex is an example of a region containing a mixed population of M1 and M2 sites. These results provide an anatomical description of the distribution of subtypes of the muscarinic receptor in the human brain, which can be related to the known pharmacological effects of muscarinic agents in brain function.

Aged↗
PubMed1986

Alzheimer's paired helical filaments share epitopes with neurofilament side arms.

A panel of monoclonal antibodies to neurofilaments have been investigated with regard to the location of their respective epitopes on neurofilament polypeptides and their ability to label the neurofibrillary tangles and paired helical filaments (PHF) which are characteristic of Alzheimer's disease. All of the neurofilament monoclonal antibodies that label tangles and PHF are directed against epitopes in the side arm domains of the two larger neurofilament polypeptides, NF-H and NF-M, and do not recognise the alpha-helical rod domains of these proteins. Immuno-electron microscopy demonstrates that the neurofilament antibodies label the constituent PHF per se and do not simply stain neurofilaments that might be admixed with PHF. These neurofilament epitopes are differentially retained by PHF, following isolation. Thus, antibody labelling of PHF is not simply due to the presence of normal neurofilament polypeptides. We propose that in tangle-bearing neurons, neurofilaments are degraded by proteases and that it is fragments of the side arms which contribute to the composition of PHF.

Alzheimer Disease↗
PubMed1986

The brain diseases causing senile dementia. A morphological study on 54 consecutive autopsy cases.

Brains from 54 patients with organic dementia were examined systematically. As in previous investigations a predominance of Alzheimer type changes was observed. Seventeen patients showed Lewy bodies in the nucleus basalis, the substantia nigra and the locus coeruleus as well as other lesions of parkinsonian type. In 5 cases these changes were thought to be responsible for dementia. In 8 patients no convincing morphological substrate of dementia was found. These patients were older than average; therefore age per se might have been responsible for dementia. It is emphasized that subjective judgements are almost unavoidable in assessing the cause of organic dementia.

Aged↗
PubMed1986

Distribution of somatostatin receptors in the human brain: an autoradiographic study.

High affinity somatostatin receptors have been measured in postmortem brains from 18 neurologically asymptomatic patients (mean age: 67 years) using the stable somatostatin analog 125I-204-090, DPhe-Cys-Tyr-DTrp-Lys-Thr-Cys-Thr(ol), as radioligand. In homogenates from human frontal cortex, high affinity (Kd = 0.52 nM; Bmax = 557 fmol/mg protein) receptors with pharmacological specificity for somatostatin, [D-Trp8]somatostatin and somatostatin-28 were found. The CNS distribution of these receptors was studied by autoradiography. Somatostatin receptors were distributed in varying densities throughout the whole brain. High concentrations are found in all cortical layers, the deeper layers (V-VI) being usually more dense than the superficial layers (I-III). The limbic system is heavily labeled, in particular hippocampus (CA1, dentate gyrus), most of the nuclei of the amygdala, and the habenula. Also parts of the basal ganglia are very rich in somatostatin receptors: the nucleus caudatus as well as the nucleus accumbens are very dense, whereas the globus pallidus is virtually unlabeled. Interestingly, significant amounts of somatostatin receptors are found in the human cerebellum, which is devoid of endogenous somatostatin. Other discrete areas of the CNS are enriched with somatostatin receptors: locus coeruleus, tuberal nuclei of the hypothalamus, claustum, tuberculum olfactorium as well as spinal trigeminal nucleus and substantia gelatinosa of the spinal cord. The substantia innominata is poor in somatostatin receptors. In general there is a good correlation in the distribution of somatostatin receptors in the human and rat brain and there is a reasonable correlation with endogenous somatostatin levels in human brain tissue, particularly in the larger structures. The very high density and the specific localization of somatostatin receptors in strategic key points in the CNS such as cortex, basal ganglia, limbic system and substantia gelatinosa suggests an important role of somatostatin in cognitive, sensory and extrapyramidal motor functions. The significance of somatostatin receptors in the human cerebellum remains to be elucidated.

Aged↗
PubMed1986

The distribution of glycine receptors in the human brain. A light microscopic autoradiographic study using [3H]strychnine.

Glycine receptors were localized autoradiographically in postmortem human brain material using [3H]strychnine as a ligand. Slide mounted tissue sections were labeled in vitro by incubation with [3H]strychnine and autoradiograms obtained using [3H]Ultrofilm. Receptor densities were quantified by computer assisted microdensitometry. No specific binding of [3H]strychnine was observed in any of the forebrain areas studied. Low densities were seen in the midbrain except for dorsal and lateral parts of the periaqueductal grey matter and the oculomotor nuclei. In pons, medulla oblongata and upper cervical cord high densities of [3H]strychnine binding sites were associated with some nuclei including the motor and sensory trigeminal nuclei, the facial and the hypoglossal nuclei. The highest densities of grains were associated with the substantia gelatinosa of the trigeminal nucleus in the medulla oblongata. A peculiar spotty distribution of [3H]strychnine binding sites were found in the gracilis and cuneatus nuclei. The distribution of glycine receptors in the human brain is comparable to that seen in the rat brain, although densities are much higher in the rat. The distribution of glycine receptors in the human brain provides an anatomical substrate for the understanding of the effects of drugs acting in these receptors, particularly strychnine.

Accessory Nerve↗
PubMed1986

Alzheimer neurofibrillary tangles contain phosphorylated and hidden neurofilament epitopes.

Three monoclonal antibodies to neurofilaments (RT97, BF10 and 147), two of which also recognised neurofibrillary tangles (RT97 and BF10), have all been shown to be specific for phosphorylated epitopes. Treatment of histological sections with alkaline phosphatase prior to immunostaining resulted in reduction of axonal neurofilament staining with all three whilst the neurofibrillary tangles staining with BF10 was unaffected. Antibody 147 was found to recognise weakly some neurofibrillary tangles following alkaline phosphatase treatment. The results presented confirm the presence of structurally abnormal but phosphorylated neurofilaments in neurofibrillary tangles.

Alkaline Phosphatase↗
PubMed1985

Beta-adrenoceptor subtypes in the human brain: autoradiographic localization.

The distribution and characteristics of beta-adrenoceptors in postmortem human brain was studied using quantitative autoradiographic techniques. 125I-Cyanopindolol was used as a ligand. High densities of beta-adrenoceptors were found in the caudate, putamen, different cortical areas and layers and the hippocampal formation. Low densities were present in other areas such as the thalamus, hypothalamus, midbrain and cerebellar cortex. Specific beta 1 and beta 2 antagonists were used to visualize and quantify separately the two subtypes of beta-adrenoceptors. Computer analysis of the competition curves obtained revealed that the putamen was enriched in beta 1 sites while the cerebellum contained predominantly beta 2 adrenoceptors. The regional distribution of beta-adrenoceptor subtypes was found to be similar to that seen in the rat brain.

Aged↗
PubMed1985

Immunohistological study of granulovacuolar degeneration using monoclonal antibodies to neurofilaments.

Neurons undergoing granulovacuolar degeneration have been examined in paraffin sections with three monoclonal antibodies to neurofilaments. Two of these antibodies (BF10, RT97) had been shown previously to react with neurofibrillary tangles. One of these antibodies (RT97) reacted with granular component of granulovacuolar degeneration. BF10 sometimes reacted with the surrounding neuronal cytoplasm. Granulovacuolar degeneration was also detected in a few cells of the anterior olfactory nucleus.

Alzheimer Disease↗
PubMed1985

[Prophylactic antibiotic therapy using oxacillin in peripheral vascular surgery of the lower limbs. Preliminary results].

The rate of postoperative infections in lower limb vascular surgery was first evaluated in a retrospective study of 416 bypass procedures (68 venous grafts and 348 prosthetic grafts) in 400 patients seen over a two-year period. 31 postoperative infections (7.4%) were found. Outcome was fatal in three cases. 70% of cases were due to a methicillin-susceptible Staphylococcus aureus. Antibiotic prophylaxis with oxacillin given during surgery and for the first 48 postoperative hours was used for the next 112 procedures (17 venous grafts and 95 prosthetic grafts) in 107 patients. The preliminary results show a fall in the rate of postoperative infection, with only 5 cases (4.4%). The only case due to a methicillin-susceptible Staphylococcus occurred after a second surgical procedure without antibiotic prophylaxis. These preliminary results are promising although the difference does not reach statistical significance. However, it is of note that no patient undergoing vascular surgery for the first time developed postoperative infection. Further prospective studies are needed to determine the optimal antibiotic prophylaxis in lower limb vascular surgery.

Bacterial Infections↗
PubMed1984

Distribution of alpha 2-adrenergic receptors in the human brainstem: an autoradiographic study using [3H]p-aminoclonidine.

The distribution of alpha 2-adrenergic receptors in the human brainstem and some forebrain areas was examined by means of an in vitro autoradiographic technique using [3H]p-aminoclonidine as a ligand. High densities of alpha 2-adrenergic receptors were observed in the dorsal motor nucleus of the Xth nerve, the nucleus of the solitary tract, the locus coeruleus and the substantia grisea centralis. Other brainstem areas presenting significant densities of alpha 2-adrenergic receptors were the substantia gelantinosa of the Vth nerve, the nucleus cuneiformis, the superficial gray layer of the superior colliculus, the cortical mantle of the inferior colliculus and the inferior olivary nuclei. Of the forebrain areas studied, the highest density was seen in the primary visual cortex. The distribution observed presents some significant differences with that previously described for the rat. The localization of alpha 2-adrenergic receptors in the human brain correlates well with the distribution of noradrenergic neurons in the human brainstem and suggests sites of action of alpha 2-adrenergic drugs in the human brain.

Adrenergic alpha-Agonists↗
PubMed1984

[Course and complications of rhabdomyolysis following heroin poisoning].

A report is presented on two patients with massive rhabdomyolysis following heroin intoxication. Due to massive muscle edema of the lower legs, both patients needed early fasciotomy to prevent compression syndrome. The two cases followed a different course as regards complications and especially renal insufficiency and disorders of serum calcium and phosphorus regulation. Pathophysiology, prevention and therapy of complications are discussed. As a result of intensive physiotherapy, the long term functional outcome was satisfactory in both cases.

Acute Kidney Injury↗
PubMed1984

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↗
PubMed1984

Quantitative light microscopic autoradiographic localization of cholinergic muscarinic receptors in the human brain: brainstem.

We have investigated the localization of muscarinic cholinergic receptors in the brainstem of eight patients free of neurological disease following quantitative autoradiography of microtome sections of postmortem tissue labeled in vitro with N-[3H]methyl scopolamine as a ligand. Receptor densities were quantified by microdensitometry with the aid of a computer assisted image analysis system. Our results reveal a heterogeneous distribution of receptor sites. High concentrations of muscarinic cholinergic receptor sites were associated with many nuclei and areas of the brainstem including the nucleus facialis (VII), hypoglossus (XII), ambiguus, the motor trigeminal nucleus (V), the nucleus solitarius, the nucleus of the lateral lemniscus, the superior and inferior colliculi, the sensory trigeminal nucleus (substantia gelatinosa), the pontine nuclei, the parabrachial nuclei, some tegmental nuclei and the periaqueductal gray matter. Very high concentrations of N-[3H]methyl scopolamine binding sites were also localized in the ventral tegmental area, the nucleus paranigralis and the nucleus ovalis. Receptor densities varied between individual brains although the relative distribution of the densities in the different nuclei was the same for all of the brains examined. Most of the brainstem nuclei containing muscarinic cholinergic receptors were enriched in high affinity agonist binding sites as shown by characteristic displacement of the ligand with carbachol. Exceptions were the substantia nigra, the nucleus olivaris inferior and the substantia gelatinosa of the fifth nerve. Receptor density values and pharmacological characteristics obtained in the cortex and basal ganglia in our cases are in good agreement with previously reported values in humans, using conventional biochemical methods. This indicates that procedures used in the autoradiographic technique are not detrimental to the pharmacological characteristics and densities of muscarinic cholinergic receptors. Our results thus clearly show the feasibility of using these techniques for the localization and quantification of muscarinic cholinergic receptors in human brain postmortem material. Furthermore, our findings indicate the potential involvement of the muscarinic cholinergic effect of acetylcholine in the normal function of many brainstem centers, including motor and sensory nuclei, visual and auditory relay nuclei and cardiovascular and respiratory-related nuclei.

Brain Stem↗
PubMed1984

How specific are periodic complexes in the diagnosis of herpes simplex encephalitis?

The specificity of localized periodic complexes (PC) in the EEG is discussed by means of a case. This patient presented rapidly evolving focal symptoms of the CNS together with fever. The EEG showed localized PCs and in the CT scan there was a hyperdense lesion in a region corresponding to the EEG finding. Postmortem examination revealed a subcortical bleeding in the temporal region. Possible mechanisms for the origin of these PCs and their diagnostic value are discussed.

Aged↗
PubMed1984

Septo-optic pituitary dysplasia. Observations on three patients.

Septo-optic pituitary dysplasia is a relatively rare but pathophysiologically interesting malformation of the brain midline structures including optic chiasm and nerves, hypothalamus, neurohypophysis and septum pellucidum. The lesion develops between the 5th and 8th week of pregnancy. The cause is unknown but heredity seems unlikely. Symptoms result from hypothalamic and neurohypophyseal insufficiency of variable severity combined with reduced vision due to hypoplasia of optic nerves and chiasm. Prognosis is variable, depending on the severity of the defect as well as on the earliest time of diagnosis followed by suitable hormone substitution and specialized care of blindness. We present the clinical course in three patients and the pathological findings in one patient who died in the 14th month of life.

Child↗