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A Probst

Publications and source records attributed to A Probst.

At least 145 records · Page 8Linked to original sources
PubMed1989

Dopamine receptors in human brain: autoradiographic distribution of D1 and D2 sites in Parkinson syndrome of different etiology.

The distribution and density of dopamine D1 and D2 receptors were examined by autoradiography in postmortem brain tissue from patients with pathological diagnosis of Parkinson's disease, status lacunaris, clinical parkinsonism without neuropathological lesions and in age-matched controls. The D1 antagonist [3H]SCH 23390 and the D2 agonist [3H]CV 205-502 were used as ligands. No significant differences in the distribution or density of D1 or D2 receptors were found in Parkinson's disease in the areas examined, including the nucleus caudatus, putamen, globus pallidus and substantia nigra. In contrast, cases presenting lacunar lesions in the striatum showed marked decreases in D1 and D2 receptor densities in this region. Patients clinically diagnosed as parkinsonians but without Parkinson's disease lesions or striatal lacunar softenings showed reduced densities of D2 receptors in the nucleus caudatus and putamen, while in the substantia nigra the densities were comparable to controls. In the basal ganglia of these cases D1 receptors were slightly decreased.

Aged↗
PubMed1989

Substance P receptors in the human spinal cord: decrease in amyotrophic lateral sclerosis.

The distribution of substance P receptors was examined by autoradiography at all levels of the human postmortem spinal cord using the ligand [125I]Bolton-Hunter substance P. Adjacent sections were used to localize substance P-like immunoreactivity by a radioimmunohistochemical technique. In the control spinal cord substance P-like immunoreactivity was found to be highly concentrated in the superficial layers of the dorsal horn, intermediolateral cell columns and lamina X, while lower levels of immunoreactivity were observed in other areas of the grey matter of the spinal cord. In contrast, high densities of substance P binding sites were localized not only to the substantia gelatinosa of the dorsal horn but also to other regions of the grey matter of the spinal cord, particularly in the area of the preganglionic sympathetic neurons in the intermediolateral cell column and in the region of the somatic motor neurons of the ventral horn. In 5 cases of amyotrophic lateral sclerosis we found a marked reduction of substance P binding, especially in the ventral horn associated with the loss of motor neurons. These results suggest a postsynaptic localization of substance P receptors to the motor neurons of the ventral horn in the human spinal cord and a role for substance P in the function of motor neurons.

Adult↗
PubMed1989

New aspects of the pathology of neurodegenerative disorders as revealed by ubiquitin antibodies.

Ubiquitin has previously been identified as a component of neuronal inclusions in neurodegenerative disorders. In this investigation, we examined tissue from cases of Alzheimer's disease (AD), Pick's disease, Parkinson's disease (PD), and progressive supranuclear palsy (PSP) to identify previously unrecognized ubiquitinated structures and to assess the evolution of neuronal inclusions. In AD, approximately 60% of neurofibrillary tangles (NFTs) that were stained with an anti-paired helical filaments (PHF) serum were identified by the ubiquitin antibodies. Extracellular NFTs were not labelled with anti-PHF but were unlabelled or weakly labelled with anti-ubiquitin antibodies. In Pick's disease, most Pick bodies were strongly labelled by the ubiquitin antibodies, and in addition some hippocampal CA1 neurones contained granular or strand-like ubiquitin-immunoreactive (IR) inclusions associated with more typical Pick bodies. Typical Lewy bodies in PD cases showed an unlabelled central core with an outer ring intensely labelled by ubiquitin antibodies. Pale bodies in pigmented substantia nigra neurones appeared as large well-defined, rounded structures without an identifiable core or peripheral zone. Some pale bodies were unlabelled by ubiquitin antibodies, but others showed labelling of variable intensity. Pale bodies which were labelled by ubiquitin antibodies tended also to be labelled by BF10, a monoclonal antibody against phosphorylated neurofilaments. We suggest that pale bodies in PD may represent stages in the formation of Lewy bodies. In addition, we observed numerous spindle-shaped ubiquitin-IR swellings of dendrites of pigmented substantia nigra neurones. In contrast to inclusions of AD and Pick's disease, the PHF-positive fibrillary neuronal inclusions of PSP were either unlabelled or only weakly labelled by ubiquitin antibodies. No ubiquitinated structures were seen in neurones from corresponding areas in aged controls. Identification of ubiquitinated proteins in neurodegenerative disorders may provide insights into molecular events associated with cell death.

Aged↗
PubMed1989

Neuropathology of the acquired immune deficiency syndrome (AIDS): a report of 135 consecutive autopsy cases from Switzerland.

Neuropathological changes were studied in a consecutive autopsy series of 135 cases, comprising 73% of all patients who died of AIDS in Switzerland between April 1981 and December 1987. Central nervous system involvement was found in 119 patients (88%), 19 of which had multiple concomitant intracerebral lesions. Among the non-viral opportunistic infections, encephalitis due to Toxoplasma gondii was most frequent and occurred in 35 patients (26%), followed by central nervous system infection with Cryptococcus neoformans, which was found in five patients (4%). Cytomegalovirus (CMV) encephalitis was present in 14 patients (10%). Disseminated microglial nodules without morphological or immunocytochemical evidence of CMV was encountered in 18 patients (13%). However, in all but two of these patients there was evidence of extracerebral CMV infection, suggesting that CMV was responsible for these nodular encephalitides. Nine patients (7%) had progressive multifocal leukoencephalopathy (PML); in five of these, demyelination was associated with extensive tissue destruction and cyst formation. HIV-associated encephalopathy was observed in 21 patients (16%) and showed two characteristic morphological patterns: progressive diffuse leukoencephalopathy (PDL) and multifocal giant cell encephalitis (MGCE). PDL was observed in 13 cases and characterized by diffuse pallor and gliosis of the cerebral and cerebellar white matter with scattered multinucleated giant cells, but without significant inflammatory response. MGCE was found in eight patients and characterized by clusters of numerous multinucleated giant cells, rod cells, macrophages, lymphocytic infiltrates and occasional necroses. In our view, PDL and MGCE represent the two opposite variants of HIV-induced encephalopathies, with overlapping intermediate manifestations.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Senile plaque neurites fail to demonstrate anti-paired helical filament and anti-microtubule-associated protein-tau immunoreactive proteins in the absence of neurofibrillary tangles in the neocortex.

Although much work has been directed recently towards unravelling the protein chemistry of neurofibrillary tangle (NFT) and senile plaque (SP) components in Alzheimer's disease, the pathogeneses of these lesions remains largely unknown and the problem of their relationship is unresolved. In particular, although paired helical filaments (PHF) have long been documented in SP neurites, we do not know if they are of pathogenetic relevance for the formation of the SP. To investigate the relationship between NFT and SP, we examined antigenic properties of proteins in SP neurites in neocortical tissues of patients with senile dementia of Alzheimer type, in the presence or absence of NFT in the same cortical area. We used two polyclonal antibodies directed against PHF and microtubule-associated protein (MAP)-tau and three monoclonal antibodies (MAbs) (RT97, BF10, 147) to phosphorylated epitopes of human neurofilament polypeptides, as well as the Gallyas silver impregnation method which specifically stains PHF in NFT and neurites. The main finding of our investigations consists in a differential pattern of immunoreactivity of SP neurites depending on the presence or absence of NFT in the neocortex. In the presence of NFT, there were numerous neuropil threads and SP neurites containing Gallyas-positive, as well as anti-PHF- and anti-tau-labelled material. In the absence of NFT in the neocortex there was a striking absence of any Gallyas-positive or PHF- and tau-immunoreactive structure in the cortical neuropil and in SP neurites, irrespective of the maturation stage of the SP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Visualizing receptors for neurotransmitters in the human brain with autoradiography.

Receptors for neurotransmitters and drugs are now well characterized at the molecular level. Thanks to the development of numerous radiolabeled molecules and to the use of autoradiography it is possible to study the characteristics and distribution of these receptors with the anatomical resolution of the microscope. We have used quantitative receptor autoradiography to examine receptors in the human brain and to study receptor alterations in neurodegenerative diseases of the human brain. Alterations in the density and distribution of receptors have been found in diseases such as amyothrophic lateral sclerosis, Huntington's Chorea, Parkinson's disease and Alzheimer's disease. In these diseases different types of receptor alterations have been found. The most characteristic ones are selective receptor losses associated with neuronal losses. Alterations such as receptor hypersensitivity due to degeneration of target areas have also been observed. In some cases no correlations between alterations of the neurotransmitters and receptors have been found. These results indicate that different receptors are associated with specific neuronal systems and could be used as markers for these neuronal populations in different pathological studies. The possibility of visualizing receptors in the living human with non-invasive techniques such as PET could lead to the future use of receptor alterations as a diagnostic tool.

Autoradiography↗
PubMed1989

Dopamine receptors in human brain: autoradiographic distribution of D1 sites.

The distribution of dopamine D1 receptors has been determined in post mortem human brain tissues using in vitro receptor autoradiography, with ([3H]N-methyl) SCH 23390 as ligand. The highest densities of dopamine D1 sites were seen in the nucleus caudatus, putamen, globus pallidus pars medialis and substantia nigra. Intermediate densities were associated with the amygdala, mammillary bodies, cerebral cortex and CA1. The remaining part of the hippocampus as well as the diencephalon, brainstem and cerebellum contained low levels of [3H]SCH 23390 binding sites. The distribution of D1 receptors in the human brain closely resembles that reported for the rat brain. In addition, there was a good correlation between the anatomical localization of D1 sites and the distribution of dopaminergic nerve terminals in the central nervous system. The densities of D1 receptors in the human brain were observed to markedly decrease with age during the first decades of life. However, no further modifications were found beyond the age of 40 years. We did not observe any significant influence of other parameters such as gender and post mortem delay in our samples.

Aging↗
PubMed1989

Dopamine receptors in human brain: autoradiographic distribution of D2 sites.

We have studied the detailed anatomical distribution of D2 receptors in human post mortem brain tissue using quantitative autoradiographic techniques. D2 receptors were labeled using the specific D2 agonist [3H]CV 205-502 and the antagonist [3H]spiroperidol. The pattern of D2 receptor distribution observed with the two ligands was very similar. The highest densities were found in the nucleus caudatus, putamen, nucleus accumbens and olfactory tubercle followed by the substantia nigra, where D2 receptors were mainly concentrated in the pars compacta. Lower but still significant densities were associated with the lateral part of the globus pallidus and CA1 and CA3 fields of the hippocampus. The medial part of the globus pallidus, the dentate gyrus and the amygdala showed low to very low densities of D2 receptors. Almost negligible amounts of binding were observed in the olfactory bulb, diencephalon, brainstem, cerebellum and most parts of the neocortex. Our results are comparable with previously reported localizations of D2 receptors in the human and rat brain. We also report the lack of the so-called spirodecanone binding sites in the human brain. The localization of D2 receptors is compared with the distribution of D1 receptors.

Aging↗
PubMed1989

Biotinidase deficiency: a cause of subacute necrotizing encephalomyelopathy (Leigh syndrome). Report of a case with lethal outcome.

An unusual clinical course of a patient with biotinidase deficiency, causing Leigh syndrome, is reported. Laryngeal stridor was the major presenting symptom followed by progressive neurologic deterioration and death at the age of 21.5 mo. Absence of skin and hair abnormalities as well as of organic aciduria delayed the correct diagnosis. Necropsy revealed subacute necrotizing encephalopathy (Leigh syndrome). Carboxylase activities (propionyl CoA carboxylase, 3-methylcrotonyl-CoA carboxylase, pyruvate carboxylase) measured in lymphocytes 1 day before death were decreased to 10% of normal values. Propionyl-CoA carboxylase was shown to be the only stable carboxylase in human postmortem tissue; in our patient it was moderately decreased in postmortem liver (29% of control) and kidney (42%), but severely decreased in brain (3%). These findings might explain the severity of neurological symptoms in the absence of marked organic aciduria. They indicate that in biotinidase deficiency the CNS may become biotin depleted earlier and more severely than other organs. Biotinidase deficiency should be included in the differential diagnosis of Leigh syndrome and of unexplained respiratory problems.

Amidohydrolases↗
PubMed1988

Decreased densities of dopamine D1 receptors in the putamen and hippocampus in senile dementia of the Alzheimer type.

The density and distribution of dopamine D1 receptors as labeled with [3H]SCH 23390 was analyzed in post-mortem brain tissue from patients with senile dementia of the Alzheimer type (SDAT) and in controls using quantitative autoradiography. In SDAT patients D1 receptor densities were markedly decreased in parts of the hippocampus, with reductions of up to 89% compared to the control values in the molecular layer of the dentate gyrus, 57% in the strata oriens and pyramidalis of the CA1 and 74% in the CA3 subfields. Significant decreases in D1 receptors were also observed in the putamen (23%) but not in the caudate and substantia nigra. A slight but not significant decrease of D1 binding was observed in most external layers of the temporal and occipital cortices.

Aged↗
PubMed1988

Neuropeptide Y-like immunoreactive neurons in the human olfactory bulb.

Neuropeptide Y-like (NPY) immunoreactivity was localized in the adult human olfactory bulb by the unlabeled antibody enzyme (peroxidase anti-peroxidase; PAP) technique in vibratome sections. The majority of NPY-immunoreactive somata was localized in the white matter surrounding the anterior olfactory nucleus. Immunoreactive neurons were less numerous within the anterior olfactory nucleus and within the olfactory bulb layers. NPY-immunoreactive fibres were present in the white matter, the anterior olfactory nucleus, and in the olfactory bulb layers. Fibres within the white matter were generally aligned in a straight path parallel to the long axis of the olfactory bulb and tract. Fibres within the anterior olfactory nucleus showed no clear orientation and displayed numerous branching points. Coiled plexus of NPY-immunoreactive fibres were present in the glomerular layer of the olfactory bulb. Additional characteristics of the NPY-immunoreactive neurons were studied after decolouring the chromogen and restaining the sections with aldehydefuchsin to demonstrate the presence of lipofuscin granules and also with gallocyanin chrome alum to stain the Nissl substance. This analysis showed that the neurons belong to the class of non-pigmented nerve cells.

Aged↗
PubMed1988

Differential modification of muscarinic cholinergic receptors in the hippocampus of patients with Alzheimer's disease: an autoradiographic study.

We have used quantitative light microscopic autoradiographic techniques to analyze changes in muscarinic cholinergic receptors in the hippocampus in Alzheimer type dementia (ATD). The density and distribution of muscarinic cholinergic receptors has been correlated with the density of neurons, neuritic plaques and neurofibrillary tangles in the CA1 subfield of the hippocampus of control and ATD patients. The number of pyramidal cells per mm2 in the CA1 sector was significantly decreased in ATD cases as compared to controls, although there were large variations among cases. The most marked reductions in cell counts were observed in patients with a history of profound dementia. The densities of muscarinic receptors, as well as the proportions of M1 and M2 subtypes, in the CA1 sector and dentate gyrus were not significantly different between ATD and old non-demented patients. Neuritic plaques, even in high numbers, did not affect the density of muscarinic receptors; moreover, the densities of receptors over the neuritic plaques did not differ from the surrounding neuropil. However, in some ATD cases there was a marked decrease in the concentration of these receptors in the CA1 sector and subiculum, with no change in the proportions of muscarinic receptor sybtypes. These patients exhibited frequent extracellular remnants of neurofibrillary tangles (ghost tangles), but scarce neuritic plaques, and were those showing severe losses of pyramidal cells. There was a significant positive correlation between the total concentration of muscarinic receptors in the CA1 and the density of pyramidal cells, suggesting that decreases in receptor concentration result from a severe neuronal loss. We observed that the ratio of muscarinic receptors per pyramidal cell was significantly increased in ATD patients. This might indicate a possible up-regulatory mechanism for muscarinic receptors in the population of remaining neurons in ATD However, decreases of receptor numbers following severe neuronal fall out suggest that compensatory mechanisms are no longer possible in such cases. The question is raised whether these differences between cases reflect different diseases or different stages of the same disease.

Aged↗
PubMed1988

Visualization of a novel serotonin recognition site (5-HT1D) in the human brain by autoradiography.

The localization of a novel serotonin (5-hydroxytryptamine, 5-HT) recognition site named 5-HT1D was studied by autoradiography in human postmortem brain material. Serotonin-1 sites were labeled with [3H]5-HT. The different subpopulations of 5-HT1 sites were investigated by the use of unlabeled selective compounds. 8-OH-DPAT (8-hydroxy-2-[N,N-di-n-propyl-amino]tetralin) was used to block [3H]5-HT binding to 5-HT1A, the beta-blocker (-)-21 009 (4-[3-ter-butyl-amino-2-hydroxy-propoxy]indol-2-carbonic acid isopropyl ester) to 5-HT1B and the ergoline mesulergine to 5-HT1C recognition sites. 5-HT1D sites were defined as the binding sites remaining when both 8-OH-DPAT and mesulergine were added to the incubation medium. Under these conditions, 5-HT1D sites represented a high proportion of total [3H]5-HT binding sites in the basal ganglia and substantia nigra. Lower proportions were observed in other brain areas such as the hippocampal formation and raphé nuclei. 5-HT1D sites thus represent the majority of 5-HT1 binding sites in the striatonigral pathway in man. This localization suggests an involvement of these sites in the mediation of serotoninergic mechanisms in basal ganglia functions and a possible role in brain diseases where these areas are known to be involved.

Autoradiography↗
PubMed1988

Beta-adrenergic receptor mediated release of tissue plasminogen activator in anaesthetized dogs.

Drugs like epinephrine or isoproterenol can enhance fibrinolytic activity of blood. It is still a matter of debate whether this effect can be totally or only partially blocked by beta-receptor blockers. We have developed a dog model for ex vivo measurement of the fibrinolytic activity using a spectrophotometric assay employing human plasminogen, chromogenic plasmin substrate and human fibrinogen-BrCN digests for the stimulation of t-PA. After i.v. administration of isoproterenol the fibrinolytic activity increased, but this could be seen only in the presence of fibrinogen-BrCN digest in the test system. This suggests that isoproterenol caused higher levels of dog t-PA. Pretreatment with the beta-blocker propranolol completely blocked the increase in t-PA.

Anesthesia↗
PubMed1988

Identification of a 5-HT1 recognition site in human brain membranes different from 5-HT1A, 5-HT1B and 5-HT1C sites.

In human caudate and cortex membranes, [3H]serotonin ([3H]5-HT) labels 5-HT1A and 5-HT1C recognition sites which show nanomolar affinity for 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin) and mesulergine respectively, whereas no 5-HT1B binding could be identified. However, the majority of the sites labelled by [3H]5-HT (greater than or equal to 60% in cortex, 90% in caudate) are different from 5-HT1A, 5-HT1B and 5-HT1C sites. Competition experiments were performed in human caudate membranes incubated with [3H]5-HT in the presence of 100 nM 8-OH-DPAT and 100 nM mesulergine. Under those conditions, [3H]5-HT labelled an apparently homogeneous population of 5-HT1-like sites which display nanomolar affinity for tryptamines (5-carboxamido-tryptamine, (5-CT) greater than 5-HT greater than or equal to 5-methoxytryptamine (5-MeOT) greater than tryptamine) and some ergolines (metergoline greater than methysergide). In contrast, these sites showed low affinity for drugs with high affinity and/or selectivity for 5-HT1A (8-OH-DPAT, buspirone), 5-HT1B (21-009, RU 24969), 5-HT1C (mesulergine, mianserin) and 5-HT2 sites (ketanserin, cinanserin). The pharmacological profile of these sites is different from that of 5-HT1A, 5-HT1B, 5-HT1C, 5-HT2 and 5-HT3 sites but is consistent with the pharmacology of a 5-HT1-like receptor. It is very similar to that of the 5-HT1D site recently described in bovine brain by Heuring and Peroutka.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Mapping dopamine receptors in the human brain.

We have investigated the anatomic localization of dopamine D1 and D2 receptors in the human brain using selective high affinity ligands for both types of dopamine receptors and the technique of receptor autoradiography. Dopamine D1 receptors were labeled in postmortem human brain tissue sections using the antagonist [3H]SCH 23390. Dopamine D2 receptors were labeled in consecutive tissue sections using the agonist [3H]205-502 and the antagonist [3H]spiroperidol. D1 and D2 dopamine receptors presented a heterogeneous distribution in the human brain. The highest concentrations of both D1 and D2 receptors were found in parts of the basal ganglia, particularly the nucleus caudatus and putamen. Lower concentrations were seen in other areas for example, the lateral globus pallidus was enriched in D2 receptors and the medial globus pallidus in D1 receptors. The substantia nigra contained intermediate densities of both D1 and D2, D1 receptors being present in higher concentrations. Dopamine D1 receptors were also localized in areas outside of the basal ganglia, particularly in the neocortex, amygdala and hippocampal formation. Dopamine D2 receptors were also present in areas outside of the basal ganglia, the most significant densities being found in the hippocampal formation. We observed a marked age-dependent decline in the density of D1 receptors during the first decades of life. In contrast, D2 receptor concentrations appeared to be unaltered with age. The distribution and densities of dopamine receptors were examined in 12 cases of Parkinson's disease and compared to a control adult population. No significant differences in density and distribution were seen for either D1 nor D2 receptors.

Adolescent↗
PubMed1988

Somatostatin-like immunoreactivity in non-pyramidal neurons of the human entorhinal region.

The distribution of somatostatin-immunoreactive cells and processes throughout the human entorhinal region and subjacent white matter was examined either by the unlabelled antibody-enzyme method or by the avidin-biotin method. The brain slices were obtained at autopsy with a short post-mortem delay. The majority of somatostatin immunoreactive nerve cells was found in the inner principal layer and subjacent white matter. In addition, individually scattered immunoreactive neurons were observed in both the outer principal layer and lamina dissecans. The immunoreactive perikarya varied in shape and ranged in size from 10 to 30 micron. Without exception the neurons could be classified as belonging to the group of non-pyramidal neurons. Each neuron gave rise to a few thick dendrites and a thin axon with a beaded appearance. In the adult human brain, the pattern formed by lipofuscin granules deposited in the nerve cells can be considered characteristic for the type of the neuron. Therefore, immunoreactive perikarya were documented, destained of chromogen and restained to demonstrate lipofuscin pigment and basophilic substance. It became evident from these studies that the previously immunoreactive cells were characterized by a large rounded and eccentrically located nucleus, sparse basophilic substance and, in most cases, a lack of lipofuscin granules. A few of the immunoreactive cells were laden with coarse pigment granules. The findings permit classification of entorhinal somatostatin-immunoreactive neurons as either non-pigmented or pigment-laden non-pyramidal neurons.

Aged↗