Search PubMed⌕ Search

Biomedical subjects

A Probst

Publications and source records attributed to A Probst.

At least 91 records · Page 5Linked to original sources
PubMed1996

Activation of meningeal 5-HT2B receptors: an early step in the generation of migraine headache?

Several pharmaceuticals are frequently dispensed to prevent or reduce the occurrence of migraine attacks. The prophylactic effect of these drugs has been suggested to be caused through blockade of serotonin (5-HT) receptors of type 5-HT2B or 5-HT2C. To elucidate which of these receptors is involved, we first used radioligand binding assays to determine the pharmacological profile of the human and rat-5-HT2B receptor. Furthermore, the potency of drugs used in migraine prophylaxis to stimulate or inhibit 5-HT2B or 5-HT2C receptor-mediated potency of drugs used in migraine prophylaxis to stimulate or inhibit 5-HT2B or 5-HT2C receptor-mediated phosphatidyl inositol hydrolysis was measured. All these drugs were found to block both human receptors. Correlation of the receptor affinities with the potencies used in migraine prophylaxis showed significant correlations, which were better for the 5-HT2B (P = 0.001) than for the 5-HT2C receptor (P = 0.005). Migraine headache is thought to be transmitted by the trigeminal nerve from the meninges and their blood vessels. Using the reverse transcription-polymerase chain reaction, the expression patterns of all cloned G-protein-coupled serotonin receptors were analysed in various human meningeal tissues. All tissues expressed 5-HT1Dbeta, 5-HT2A, 5-HT2B, 5-HT4 and 5-HT7 mRNAs. Only trace amounts of 5-HT2C receptor mRNA were found. With organ bath experiments we showed that the 5-HT2B receptor stimulated the relaxation of the pig cerebral artery via the release of nitric oxide. Our data support the hypothesis that 5-HT2B receptors located on endothelial cells of meningeal blood vessels trigger migraine headache through the formation of nitric oxide.

Animals↗
PubMed1996

Fatal vascular leak syndrome with extensive hemorrhage, peripheral neuropathy and reactive erythrophagocytosis: an unusual complication of recombinant IL-3 therapy.

A 39-year-old patient with severe aplastic anemia (AA), resistant to therapy, received recombinant human IL-3 (rhIL-3) on a phase I/II trial. During treatment she developed disseminated skin lesions, suggestive of vasculitis, and severe progressive peripheral neuropathy culminating in complete paralysis. She died 25 days after beginning treatment from profuse bleeding. On autopsy, evidence of vascular leaks with widespread bleeding and extensive hemorrhagic involvement of peripheral nerves was found. An additional feature was massive reactive erythrophagocytosis in lymph nodes, spleen and bone marrow. The coincidence between rhIL-3 administration and the dramatic events suggest a causal relation. As a possible pathogenic mechanism, an rhIL-3 induced excessive stimulation of macrophages and production of secondary cytokines such as tumor necrosis factor (TNF) is suggested. TNF is considered as a major factor in the development of both a vascular leak and reactive erythrophagocytosis. This case report can be regarded as an example of the possible unusual pathologic phenomena we may expect to see in the near future with increasing use of growth factors.

Adult↗
PubMed1996

Acute disseminated encephalomyelitis: MR and CT features.

We describe three cases of acute disseminated encephalomyelitis (an immune-mediated inflammatory demyelinating disease of the central nervous system) and their histology, showing different radiological features. One appearance is a few ring-shaped enhancing lesions, which are found predominantly in the supratentorial white matter, the other is solid disseminated lesions.

Adult↗
PubMed1995

Somatodendritic localization and hyperphosphorylation of tau protein in transgenic mice expressing the longest human brain tau isoform.

Microtubule-associated protein tau is the major constituent of the paired helical filament, the main fibrous component of the neurofibrillary lesions of Alzheimer's disease. Tau is an axonal phosphoprotein in normal adult brain. In Alzheimer's disease brain tau is hyperphosphorylated and is found not only in axons, but also in cell bodies and dendrites of affected nerve cells. We report the production and analysis of transgenic mice that express the longest human brain tau isoform under the control of the human Thy-1 promoter. As in Alzheimer's disease, transgenic human tau protein was present in nerve cell bodies, axons and dendrites; moreover, it was phosphorylated at sites that are hyperphosphorylated in paired helical filaments. We conclude that transgenic human tau protein showed pre-tangle changes similar to those that precede the full neurofibrillary pathology in Alzheimer's disease.

Alzheimer Disease↗
PubMed1995

Alzheimer's changes in non-demented and demented patients: a statistical approach to their relationships.

The anterior hippocampus and the entorhinal cortex of 167 non-demented individuals (controls) and 22 patients with Alzheimer's dementia were investigated. Senile plaques and neurofibrillary tangles were counted on paraffin sections stained with methenamin silver and Gallyas silver iodide, respectively. The results showed that both senile plaques and neurofibrillary tangles areal densities (lesions per mm2) correlated significantly with age in the control collective. No significant correlation between Alzheimer's disease lesions and age was found in patients with Alzheimer's dementia. Positive and significant correlation between senile plaques and neurofibrillary tangles was found in the control group but not in the Alzheimer group. Control individuals (n = 43, matched for age with the Alzheimer group) displayed both plaques and tangles. In this subgroup neither plaques nor tangles correlation with age; however, there was a significant correlation between senile plaques and neurofibrillary tangles. We hypothesize that the continuous activity of underlying processes associated with senile plaques and neurofibrillary tangles formation or resolution might lead to the unbalanced production of these lesions in Alzheimer's disease.

Adult↗
PubMed1995

Alzheimer's disease-type neurofibrillary degeneration in verrucose dysplasias of the cerebral cortex.

Verrucose dysplasias, found at autopsy in the cerebral cortex of three elderly individuals (two without neurological disorders and one with motor neuron disease), are shown to present neurofibrillary degeneration of Alzheimer's disease type. This neurofibrillary degeneration immunoreacted with antibodies against abnormally phosphorylated tau (5E2 and AT8), disclosed acetyl- and butyrylcholinesterase activity, and was consistently stained with thioflavin-S. Cortical dysplasias, found either as isolated verrucose nodules or comprising multiple nodules, contained cell-sparse areas around which a peak of neurofibrillary changes was seen. Cell-sparse areas were sometimes bridged by stripes of neurons and fibers arranged in a radial fashion, and many of these neurons showed neurofibrillary degeneration. Cytoskeletal abnormalities were conspicuous in layers II and III at the external borders of the dysplasias, as well as in neurons located in layers V and VI, and in the white matter beneath layer VI in central zones of each lesion. The morphology of cells undergoing neurofibrillary changes (from early non-fibrillar stages to late extracellular ones) suggests that neurons disturbed in their migration toward the site to which they had been committed may become vulnerable to cytoskeletal changes. Micro-environmental disturbances related to hypoxia-ischemia in the affected cortex are proposed as likely contributing factors for the long-term production of this neurofibrillary degeneration.

Aged↗
PubMed1995

Frontal lobe degeneration: novel ubiquitin-immunoreactive neurites within frontotemporal cortex.

Ubiquitin-protein conjugates have been identified in filamentous inclusions in various neurodegenerative disorders. In frontal lobe degeneration (FLD) no distinctive histological features have been reported with the exception of some ubiquitin-positive intraneuronal inclusions in cases associated with motor neuron disease. In the present study, we investigated five FLD cases without motor neuron disease using immunohistochemistry. A constant feature in all cases consisted of ubiquitin-positive neurites in layers I-III of the frontotemporal neocortex. These neurites were not argyrophilic, and could not be labelled with various antibodies against tau and neurofilament proteins. Ubiquitin-protein conjugates were found in distended dendritic branches, in dendritic spines and in smooth slender neurites, probably axons. No ubiquitinated neurites were seen in corresponding areas of the brain in aged controls. The nature of ubiquitinated proteins in FLD and the reason why they are confined to nerve cell processes is unknown but may be understood as part of an ongoing process leading to cell death observed in FLD.

Aged↗
PubMed1995

Brain irradiation and antioedematous dexamethasone treatment--risk factors for herpes simplex encephalitis?

Herpes simplex encephalitis (HSE) could result from the reactivation of an endogenous latent herpes simplex virus (HSV) in sensory ganglia or in brain parenchyma. Virus replication and a new lytic virus cycle may be triggered by a wide variety of factors. One of these might be irradiation as suggested by experimental evidence obtained in mouse trigeminal ganglia. Here we report the occurrence of HSE in a 52 years old woman two months after brain irradiation (40 Gray in 20 fractions) and dexamethasone administration for a metastatic brain tumor. HSE has already been observed in a clinical context very similar to that reported here, suggesting that brain irradiation together with corticoid therapy may, in some rare patients, favour the occurrence of HSV reactivation and HSE.

Antineoplastic Agents, Hormonal↗
PubMed1994

Distinct Streptococcus thermophilus bacteriophages share an extremely conserved DNA fragment.

A cross-hybridizing 2.2-kb EcoRI fragment was cloned from two lytic Streptococcus thermophilus bacteriophages with distinct phenotypes. The DNA fragments, which contained two unidentified open reading frames, differed at only 3 of 2207 nucleotide positions. Partial sequencing of a temperate S. thermophilus phage and of a further lytic phage belonging to a different lytic group isolated 20 years earlier from a different geographical area confirmed this extreme sequence conservation. Hybridization of this phage DNA with bacterial host DNA was not observed. The evolutionary implications of these observations are briefly discussed.

Amino Acid Sequence↗
PubMed1994

[The neuron theory: one of the main scientific achievements of the 19th century].

The cell theory, enunciated by Theodor Schwann in 1839, stated that all tissues in the body are composed of individual cells. The theory gained immediate acceptance for all organs except for the nervous system where some basic problems were encountered, among them the difficulties in establishing the relation between nerve cells, nerve fibers and terminal branches. Deiters observations (1865) had provided evidence that the basic structure of a nerve cell was made up of a cell body, protoplasmic prolongations (dendrites), and a single long axon. This helped to define the nerve cell as the basic unit of the nervous tissue but it remained then to understand how the nerve cells are connected since they do not make direct contact through their cell bodies and are separated by the 'neuroglia'. Two fundamentally different views of the organization of neurons arose, one holding that neurons are individual and contiguous units, connected in chains to form specific pathways (His, Forel, Nansen, Ramón y Cajal), the other that thin nerve cell branches from continuous diffuse networks through which the neuronal activity propagates (Gerlach, Golgi). The key technological advance that led to the resolution of most of these uncertainties came in 1873 with the introduction by Camillo Golgi of a new method of staining individual nerve cells. In 1887, Santiago Ramón y Cajal stumbled on the Golgi stain and began an intense study of neuronal morphology throughout the nervous system. As far back as 1887 it was shown that the nervous system is not a mass of fused cells showing a common cytoplasm, but a highly intricate network of discrete cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Europe↗
PubMed1994

Levels of water-soluble antioxidants in astrocytoma and in adjacent tumor-free tissue.

The aim of the present study was to investigate the oxidative status in astrocytoma. Samples of brain tissue from the centre to the periphery of the tumor were obtained from 11 astrocytoma patients undergoing computer tomography-guided stereotaxic operation, who had been previously treated with the corticosteroid dexamethasone. Part of the sample was investigated histologically for clarification of tumor type, and the presence of neoplastic and non-neoplastic tissue and necrosis. The rest was used for the quantification of the antioxidants ascorbic acid, uric acid, glutathione and cysteine by high performance liquid chromatography, and for quantification of DNA. Levels of antioxidants were calculated as micrograms/g fresh tissue and mumol/g DNA, a parameter related to cell content. There was significantly more DNA in neoplastic samples than in non-neoplastic ones, indicating increased cell density. Uric acid (micrograms/g fresh tissue) was significantly increased in neoplastic compared with non-neoplastic tissue, and levels were even higher in necrotic tissue. There were no significant differences between neoplastic and non-neoplastic tissue levels of ascorbic acid, glutathione or cysteine, expressed as micrograms/g fresh tissue. However, when levels of these three compounds were expressed as mumol/g DNA, i.e. taking into account the higher cell density, ascorbic acid, glutathione and cysteine were significantly reduced in neoplastic samples compared with non-neoplastic ones. Results thus show that there are differences between the antioxidant levels in astrocytoma and non-neoplastic tissue, providing additional support for the hypothesis that free radicals play a role in tumor growth.

Adult↗
PubMed1994

A comparative autoradiographic study of 5-HT1D binding sites in human and guinea-pig brain using different radioligands.

Quantitative receptor autoradiography was used to examine the 5-hydroxytryptamine (5-HT, serotonin) binding sites labelled with serotonin-5-O-carboxymethyl-glycyl-[125I]tyrosinamide ([125I]GTI) in human and guinea-pig brain. Competition experiments using 5-carboxamidotryptamine (5-CT), 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (CP 93129) and sumatriptan revealed monophasic displacement curves in various brain regions, suggesting that a homogeneous population of 5-HT1D binding sites was labelled. Displacement of [3H]5-HT (in the presence of 100 nM 8-hydroxy-2(N-dipropylamino)tetralin (8-OH-DPAT) and 100 nM mesulergine) with unlabelled GTI resulted in monophasic competition curves in substantia nigra, globus pallidus and central gray. In contrast, biphasic displacement was observed in hippocampus, nucleus accumbens, claustrum, caudate-putamen and frontal cortex. The distribution of [125I]GTI sites was compared to that of [3H]5-HT binding sites (under so-called '5-HT1D conditions', i.e. in the presence of 100 nM 8-OH-DPAT and 100 nM mesulergine, in order to block 5-HT1A and 5-HT1C sites, respectively) in human and guinea-pig brain. Qualitative analysis revealed differences in the distributions of [125I]GTI and [3H]5-HT binding sites. Regions such as CA3 and CA4 of the hippocampus, claustrum and putamen showed [3H]5-HT binding (under '5-HT1D conditions') but no [125I]GTI binding sites, indicating that [3H]5-HT labels besides a GTI sensitive (5-HT1D) receptor population, a non-5-HT1A/1B/1C/1D [3H]5-HT binding site in human and guinea-pig brain. The distribution of these non-5-HT1A/1B/1C/1D [3H]5-HT binding sites was studied with [3H]5-HT under conditions where 5-HT1A, 5-HT1C and 5-HT1D [3H]5-HT binding sites were saturated by the presence of 100 nM 8-OH-DPAT, 100 nM mesulergine and 1 microM GTI. Significant densities of these non-5-HT1A/1B/1C/1D sites were observed in cortical areas, hippocampal structures, nucleus accumbens, amygdala, caudate-putamen and claustrum. It is concluded that [125I]GTI does not label the 5-HT1E binding site, since all competition curves obtained with this radioligand were monophasic. By contrast, [3H]5-HT labels non-5-HT1A/1B/1C/1D [3H]5-HT binding sites, but it remains to be established whether these sites represent a single receptor population.

Aged↗
PubMed1994

Excitatory amino acid AMPA receptor mRNA localization in several regions of normal and neurological disease affected human brain. An in situ hybridization histochemistry study.

In situ hybridization histochemistry was used to localize the mRNAs coding for four alpha-aminoisoxazole propionic acid-sensitive glutamate receptor subunits in human brain (age range 51-95 years, postmortem delay 4.5-10 h). High levels of the B receptor subunit mRNA were present in all the studied regions, followed by the A-subunit and the C-subunit. Only very low levels of the D-subunit mRNA were detected. In hippocampus, the mRNA coding for the B-subunits of the glutamate receptor was observed in granule cells of dentate gyrus and in the pyramidal cells of Ammon's horn. In cortex, the highest levels of glutamate receptor subunit mRNAs were found in layer I and layers III-IV of entorhinal and temporal cortex, although significant levels were also observed in the other cell layers. A differential distribution was seen in cerebellum where the A-subunit mRNA is expressed mainly by Purkinje cells, while the B-subunit mRNA is present in the internal granule cell layer. These results correlate well with previous data from autoradiographic studies on the localization of excitatory amino acid binding sites in human brain and pinpoint the cells where these receptors are synthesized. In situ hybridization in the hippocampus of patients affected by Alzheimer's disease (age range 77-82 years, postmortem delay 19-25.5 h) revealed a decrease on the content of the mRNAs coding for these excitatory amino acid receptors, while an increase was detected in surgically dissected epileptic human hippocampi. These results corroborate and extend the previous data from in vitro autoradiography and suggest alteration of the excitatory amino acid disfunction during these neurodegenerative processes.

Adolescent↗
PubMed1994

Accumulation of a 50 kDa N-terminal fragment of beta-APP695 in Alzheimer's disease hippocampus and neocortex.

Proteolytic processing of beta-amyloid precursor protein (beta-APP) is a key event in the formation of beta-amyloid deposits in Alzheimer's disease (AD) brains and is likely to be accompanied by the accumulation of cleavage products other than the beta/A4 protein. Using a beta-APP695-specific monoclonal antibody in quantitative immunoblotting, a 50 kDa N-terminal fragment of beta-APP695 was detected in neocortex, hippocampus and cerebellum of AD patients and control individuals. The mean level of this fragment was higher in AD hippocampus and neocortex as compared to controls, suggesting that beta-APP695 fragments are generated in various brain regions but that the proteolytic processing is increased in pathologically affected brain areas.

Adult↗
PubMed1994

[Preoperative MR-mammography in diagnosed breast carcinoma. Useful information or useless extravagance?].

In a retrospective study the value of MR mammography in cases of radiological well-known carcinoma of the breast was evaluated preoperatively in 76 cases of histopathologically verified carcinoma one lesion was missed by MR imaging. Compared to the results of conventional X-ray mammography additional malignant lesions were detected in 5 patients ipsilaterally and in another 8 patients contralaterally by MR mammography only. In additional 4 cases MR mammography demonstrated suspicious lesions contralaterally, but histopathology revealed benign lesions. The therapeutic procedure was changed in 15 cases (18.5%) due to the findings of MR imaging: Ipsilateral mastectomy instead of tumorectomy (n = 5) or primary chemotherapy instead of operation (n = 1); contralateral additional tumorectomy (n = 3) or mastectomy (n = 2) by carcinoma and open biopsy (n = 4) by benign finding.

Adult↗
PubMed1993

Characterization of proteases with the specificity to cleave at the secretase-site of beta-APP.

The beta-amyloid precursor protein (APP) can be proteolytically processed in at least two different ways either in a secretory pathway or in a lysosomal pathway. The proposed sites for the 'secretase' cleavage are the Gln15-Lys16 and Lys16-Leu17 peptide bonds within the beta A4 domain. Using chromogenic peptide substrates derived from these APP sites, proteolytic enzymes were investigated in the brain of AD patients and control individuals. Mean differences in enzyme activity were observed between the two groups, although no statistical significance was reached. Further analysis in rat brain allowed identification of the lysosomal cathepsin B and the cytosolic proteasome as secretase-like enzymes. They are probably not involved in APP secretion but possibly in removal of amyloidogenic fragments.

Alzheimer Disease↗