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Biomedical subjects

A Probst

Publications and source records attributed to A Probst.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1993

Beta APP gene expression is increased in the rat brain after motor neuron axotomy.

The response of the beta APP gene to neuronal injury was studied in the facial and hypoglossal nerve nuclei of the rat after corresponding nerve axotomy. Increased levels of beta APP 695, 714, 751 and 770 mRNAs were observed after either facial or hypoglossal nerve axotomy in the parent ipsilateral motor neurons. The increase was gradual, with maximal values 7 days after axotomy. beta APP mRNA expression returned to normal values 60 days after the lesion. Increased beta APP immunostaining was also detected in ipsilateral chromatolytic motor neurons. No change in beta APP immunoreactivity was observed in oligodendrocytes, another cell type expressing beta APP under normal conditions. A rapid increase in the expression of the GFAP gene was observed in reactive astrocytes surrounding chromatolytic neurons in the ipsilateral facial or hypoglossal nuclei. Thus, in contrast with other models of neuronal injury, where only the Kunitz protease inhibitor-containing beta APP mRNA isoforms are increased, all beta APP mRNAs are increased in the axotomy model. Furthermore, although beta APP expression has been shown to be increased in reactive astrocytes following neuronal injury, in the present study the increase was essentially found in the motor neurons reacting to axotomy.

Amyloid beta-Protein Precursor↗
PubMed1993

Increased levels of the Kunitz protease inhibitor-containing beta APP mRNAs in rat brain following neurotoxic damage.

Deposits of beta-amyloid are one of the main pathological characteristics of Alzheimer's disease. The beta-amyloid peptide (or beta/A4) constituent of these deposits is derived from the beta-amyloid precursor protein (beta APP), which is expressed in several isoforms. It has been suggested that an imbalance in the normal ratio between the Kunitz protease inhibitor (KPI)-containing beta APPs versus the non containing forms could result in altered processing of beta APP and progressive beta/A4 deposition. We have studied the expression of four beta APP isoforms in the rat brain after intracerebroventricular application of kainic acid. Increased levels of the KPI-containing beta APP and GFAP mRNAs were observed in tissues surrounding areas of neuronal damage. A parallel increase of beta APP and GFAP immunoreactivity was observed in reactive astrocytes in these areas. These results suggest that the normal ratio of beta APP isoforms may be profoundly altered as a result of neuronal damage and that non-neuronal cells may respond to neuronal injury by increased expression of the KPI-containing beta APP isoforms.

Amyloid beta-Protein Precursor↗
PubMed1993

Expression of acetylcholinesterase messenger RNA in human brain: an in situ hybridization study.

The distribution of messenger RNA coding for acetylcholinesterase was studied in human post mortem brain and rhesus monkey by in situ hybridization histochemistry and compared to the distribution of acetylcholinesterase activity. Acetylcholinesterase messenger RNA had--similar to acetylcholinesterase enzymatic activity--a widespread distribution in human bain. Acetylcholinesterase messenger RNA positive cells corresponded to perikarya rich in acetylcholinesterase activity in most but not all regions. Examples for mismatches included the inferior olive and human cerebellar cortex. The presence of hybridization signals in cerebral cortex and an enrichment in layer III and V of most isocortical areas confirmed that perikaryal acetylcholinesterase in cerebral cortex is of postsynaptic origin and not derived from cholinergic projections. In striatum the expression of high levels of acetylcholinesterase messenger RNA was restricted to a small population of large striatal neurons. In addition, low levels of expression were found in most medium sized striatal neurons. Cholinergic neurons tended to express high levels of acetylcholinesterase messenger RNA whereas in cholinoceptive neurons the levels were moderate to low. However, some noncholinergic neurons like dopaminergic cells in substantia nigra, noradrenergic cells in locus coeruleus, serotoninergic cells in raphé dorsalis, GABAergic cells in thalamic reticular nucleus, granular cells in cerebellar cortex and pontine relay neurons expressed levels comparable to cholinergic neurons in basal forebrain. It is suggested that neurons expressing high levels of acetylcholinesterase messenger RNA may synthesize acetylcholinesterase for axonal transport whereas neurons with an expression of acetylcholinesterase confined to somatodendritic regions tend to contain lower levels of acetylcholinesterase messenger RNA.

Acetylcholinesterase↗
PubMed1993

Serotoninergic terminal transporters are differentially affected in Parkinson's disease and progressive supranuclear palsy: an autoradiographic study with [3H]citalopram.

Receptor autoradiography with [3H]citalopram as ligand was used to study the distribution of serotonin uptake binding sites in post mortem brain tissues from patients with Parkinson's disease, progressive supranuclear palsy and from age-matched controls. Significant decreases in [3H]citalopram binding sites were found in the cerebral cortex of patients with Parkinson's disease and progressive supranuclear palsy. Densities of [3H]citalopram binding sites were significantly reduced in all components of the basal ganglia of Parkinson's disease but only in the head of caudate nucleus of progressive supranuclear palsy patients. The density of [3H]citalopram binding sites in the raphe nuclei of Parkinson's disease was comparable to control values. Our results suggest that serotoninergic terminals are differentially affected in Parkinson's disease and in progressive supranuclear palsy.

Aged↗
PubMed1993

Differential regional and cellular distribution of beta-amyloid precursor protein messenger RNAs containing and lacking the Kunitz protease inhibitor domain in the brain of human, rat and mouse.

The beta-amyloid precursor protein is the precursor of the main component of senile plaques (the beta-amyloid peptide or beta/A4) found in the brain of aged humans and, in higher amounts, in the brain of Alzheimer's disease and Down's syndrome subjects. Four different forms of beta-amyloid precursor protein messenger RNAs have been described in humans and rodents: beta-amyloid precursor protein 695, beta-amyloid precursor protein 714, beta-amyloid precursor protein 751 and beta-amyloid precursor protein 770 messenger RNAs (numbers corresponding to the number of encoded amino acids). The two latter forms are characterized by containing in their sequence a region with high homology to the Kunitz family of serine protease inhibitors. We have used oligonucleotide probes to study the distribution of the different messenger RNAs encoding each of the four beta-amyloid precursor proteins by in situ hybridization histochemistry in human, rat and mouse brain. We found that beta-amyloid precursor protein 695, beta-amyloid precursor protein 714 and beta-amyloid precursor protein 751 messenger RNAs were widely distributed in the human, rat and mouse brain and that their distribution was roughly similar in most brain areas in these three species. The distribution of beta-amyloid precursor protein 770 messenger RNA was not so wide and differed among the three species studied. beta-amyloid precursor protein 751 and 770 messenger RNAs were the only forms present at significant levels in rodent choroid plexus and meninges, while beta-amyloid precursor protein messenger RNA isoforms containing and lacking the Kunitz domain were detected in the human choroid plexus. We also observed that the relative levels of beta-amyloid precursor protein 751 and 770 messenger RNAs in the rat cerebral white matter as well as in the mouse and human striatum were higher than those of the beta-amyloid precursor protein messenger RNAs lacking the Kunitz domain. While the most abundant beta-amyloid precursor protein messenger RNAs in the brain of all three species under study were, in descending order, beta-amyloid precursor protein 695 and beta-amyloid precursor protein 751 messenger RNAs, the least abundant form was not the same for all species: in human it was beta-amyloid precursor protein 714 messenger RNA and in rat and mouse brain it was beta-amyloid precursor protein 770 messenger RNA. Our results show differences both inter- and intraspecies of the relative abundance and distribution of four beta-amyloid precursor protein messenger RNAs in rat, mouse and human brain.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

["Psychogenic" bulbar paralysis].

This 58-year-old female presented with a history of difficulties in swallowing for 30 years. No diagnosis was made in spite of repeated investigations including barium-contrast radiography. A probative strumectomy and psychotherapy were unsuccessful. After an episode of major depression the swallowing disturbances increased. In addition the patient complained of mastication difficulties and was dysarthric. Finally, neurological examination and neurophysiological studies established the diagnosis of progressive bulbar palsy.

Bulbar Palsy, Progressive↗
PubMed1992

Regional distribution of neuropeptide somatostatin gene expression in the human brain.

The regional distribution of mRNA coding for the neuropeptide somatostatin has been studied in the human brain by in situ hybridization histochemistry using 32P-labeled oligonucleotides. We show that somatostatin mRNA-containing neurons are widely distributed in a number of nuclei and grey areas of the human brain, including neocortex, putamen, nucleus caudatus, nucleus accumbens, amygdala, midbrain, medulla oblongata, hippocampal formation, reticular nucleus of the thalamus, and posterior nucleus of the hypothalamus. No significant hybridization signal was observed in the substantia nigra, claustrum, globus pallidus, thalamus, and cerebellum. The topographic localization of neurons containing SOM mRNA in the human brain is in agreement with previous studies using immunocytochemical or radioimmunoassay techniques. These results show that in situ hybridization histochemistry with oligonucleotide probes can be used to map the distribution of neurons expressing SOM mRNA in human postmortem materials.

Adult↗
PubMed1992

Neuron-associated class III beta-tubulin isotype, retinal S-antigen, synaptophysin, and glial fibrillary acidic protein in human medulloblastomas: a clinicopathological analysis of 36 cases.

Surgical specimens from 36 medulloblastomas (25 classic and 11 desmoplastic) were studied by peroxidase-antiperoxidase (PAP) immunohistochemistry with antibodies against the class III beta-tubulin isotype (beta-tubulin), synaptophysin, retinal S-antigen (S-Ag), and glial fibrillary acidic protein (GFAP). We found that neoplastic cells expressed beta-tubulin in 91% of the tumors (23 classic and 10 desmoplastic), synaptophysin in 75% (19 classic and 8 desmoplastic), S-Ag in 44% (11 classic and 5 desmoplastic), and GFAP in 11% of medulloblastomas (2 classic and 2 desmoplastic). Synaptophysin and beta-tubulin positivities were observed in undifferentiated neoplastic cells, in cells forming neuroblastic rosettes, and in pale islands, while S-Ag immunopositivity was noted in undifferentiated cells, occasionally in beta-tubulin-negative neuroblastic rosettes, and exceptionally in pale islands. Large pale islands, in two desmoplastic medulloblastomas, exhibited distinct patterns of immunoreactivity to the above markers, suggesting neuronal and glial differentiation in the central area, and intense neuritic development in the peripheral zone. Our findings confirm the predominant capacity of medulloblastoma cells to differentiate along neuronal cell lines and indicate that large pale islands, in desmoplastic medulloblastomas, represent well-organized areas for neuronal and, to a lesser degree, astroglial differentiation. Furthermore, it appears, in our cases, that immunohistochemical features do not represent clear-cut prognostic indicators in patients with medulloblastomas.

Adolescent↗
PubMed1992

Relationships between Lewy bodies and pale bodies in Parkinson's disease.

The prevalence of pale bodies and Lewy bodies was studied in the substantia nigra of 12 patients with typical Parkinson's disease (PD), in 5 patients with diffuse Lewy body disease (DLBD), and in a group of neurologically normal controls. Anti-ubiquitin antibodies labelled pale bodies and Lewy bodies in typical PD and DLBD, and there was a strong positive correlation between numbers of ubiquitin-immunoreactive pale bodies and Lewy bodies. BF10, a monoclonal antibody against a phosphate-dependent epitope of neurofilament 155-kDa polypeptide subunit, immunolabelled 57% of Lewy bodies and 15% of pale bodies in typical PD. Some pale bodies and Lewy bodies were seen in the substantia nigra of 2 of 5 neurologically normal, aged controls, probably representing "incidental PD". We conclude that there is a close relationship between pale bodies and typical Lewy bodies in the substantia nigra in clinical varieties of PD, and that these inclusions share antigenic determinants. If pale bodies and Lewy bodies reflect separate aspects of the cellular pathology in PD, their formation probably occurs in parallel. Alternatively, these observations may suggest that pale bodies represent a stage in the formation of Lewy bodies.

Aged↗
PubMed1992

Visualization of dopamine D1, D2 and D3 receptor mRNAs in human and rat brain.

Using 32P-labelled oligonucleotides derived from the coding regions of dopamine D1, D2 and D3 receptor mRNAs we localized cells containing transcripts for these receptors in the human (hD1, hD2) and rat brain (rD1, rD2, rD3). Dopamine D1 receptor mRNA was detected at high levels in neurons of the caudate and putamen as well as in the nucleus accumbens in both human and rat brain. In the rat brain D1 receptor mRNA was also abundant in the olfactory tubercles and several thalamic nuclei. In both species D1 mRNA was absent from the neurons of the substantia nigra and the ventral tegmental area as well as from the globus pallidus medialis in humans and entopeduncular nucleus in rats. In contrast, dopamine D2 receptor mRNA was found in dopaminergic neurons of the substantia nigra pars compacta and of the ventral tegmental area. In addition high levels of D2 mRNA were detected in neurons of the caudate, putamen and accumbens nuclei, the olfactory tubercle and the anterior lobe of pituitary gland. In the rat the highest level of hybridization was found in the intermediate lobe of the pituitary gland. In the rat brain dopamine D3 mRNA was mainly detected in the Islands of Calleja and at lower levels in the anterior nucleus accumbens, the medial mammillary nucleus as well as in the bed nucleus of the stria terminalis. In general, a good agreement was found between the distribution of transcripts and binding sites labelled with the D1 antagonist SCH 23390 or with the D2 ligand SDZ 205-502. For D1 receptors, the main exceptions were the absence of mRNA in the globus pallidus and the substantia nigra despite the high densities of binding sites in these regions. For D2 receptors, regions where binding sites but not mRNA were detected included the olfactory bulb, neocortex, hippocampus and superior colliculus.

Animals↗
PubMed1992

Mesostriatal and mesolimbic dopamine uptake binding sites are reduced in Parkinson's disease and progressive supranuclear palsy: a quantitative autoradiographic study using [3H]mazindol.

It has been suggested that not only mesostriatal but also mesolimbic pathways are involved in the degeneration of dopaminergic neurons in Parkinson's disease. Using quantitative ligand autoradiography we have investigated dopamine transporter sites in basal ganglia of patients affected by Huntington's chorea, Parkinson's disease and progressive supranuclear palsy. [3H]Mazindol, a ligand for catecholamine uptake, was used in the presence of desipramine to block the binding to norepinephrine uptake sites. Schizophrenic cases were entered in the study to take into account the effects of neuroleptics, commonly administered also to Huntington's disease patients, on dopamine uptake sites. In control cases high densities of [3H]mazindol binding sites were found in the caudate nucleus, putamen and nucleus accumbens, whereas very low densities were present in substantia nigra and ventral tegmental area. In Huntington's chorea the density of [3H]mazindol binding sites was slightly decreased in the caudate nucleus, an area severely affected by the neurodegenerative process. In schizophrenic patients the density of dopamine uptake sites in the basal ganglia was slightly reduced, mainly in the middle third of putamen. Both Parkinson's disease and progressive supranuclear palsy populations were characterized by a marked loss of [3H]mazindol binding sites in the neostriatum (about 75%) and in the nucleus accumbens (about 65%). These results suggest that in Parkinson's disease and progressive supranuclear palsy severe decreases of dopamine uptake sites occur not only in the mesostriatal pathway but also in the mesolimbic tract.

Aged↗
PubMed1992

In situ hybridization histochemistry in the human hypothalamus.

We have seen that mRNA for several neuropeptides can be visualized at the microscopic level in human post-mortem brain tissues using in situ hybridization histochemistry and oligonucleotides as probes. The specificity of the hybridization signal detected in each case is supported by several criteria such as Northern blot analysis, use of at least two oligonucleotides complementary to different regions of the same target mRNA, cohybridization of labeled and excess unlabeled oligonucleotide probes, and melting curve analysis of the formed hybrids. Furthermore, factors such as age, post-mortem delay or gender did not show a significant effect in the levels of hybridization in the control population studied. Hybridization signals comparable to those found in the control population were obtained in frozen tissues, stored for up to 6 years before analysis. The results obtained for the different neuropeptides examined are, in general, in good agreement with the available information on their distribution and cellular localization as determined by radioimmunoassay or immunohistochemistry. The use of in situ hybridization histochemistry has clearly revealed the location of neurons synthesizing these neuropeptides, adding important information to that provided by radioimmunoassay or immunohistochemistry. A typical example is the identification of peptide synthesizing neuronal cell bodies by immunohistochemistry. This requires, in some cases, the use of treatments such as colchicine, obviously impossible with human brain tissues. The abundance of mRNA could be further related to transcriptional activity and, when compared with peptide levels, can provide some clues on peptide turnover rates. Thus in the hypothalamus, the paraventricular and supraoptic nuclei were found to contain cells expressing arginine-vasopressin and oxytocin mRNAs. Their distribution was in good agreement with that determined by immunohistochemistry (Dierickx and Vandesande, 1977). We have also found that these nuclei contain transcripts for neuropeptide genes such as preproenkephalin A, neuropeptide Y and somatostatin, in agreement with previously reported immunohistochemical data (Agid and Javoy-Agid, 1985; Emson et al., 1986). In the basal ganglia, numerous cells heterogeneously distributed throughout the caudate and putamen nuclei were found to contain preproenkephalin A mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)

Basal Ganglia↗