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P L Lantos

Publications and source records attributed to P L Lantos.

At least 19 recordsLinked to original sources
PubMed1992

Prion protein immunocytochemistry helps to establish the true incidence of prion diseases.

Creutzfeldt-Jakob disease (CJD) and Gerstmann-Strüssler-Scheinker disease (GSSD) are transmissible spongiform encephalopathies or prion diseases affecting man. It has been reported that prion diseases may occur without the histological hallmarks of spongiform encephalopathies: vacuolation of the cerebral grey matter, neuronal loss and astrocytosis. These cases without characteristic neuropathology may go undiagnosed and consequently the true incidence of transmissible dementias is likely to have been under-estimated. Immunocytochemistry using antibodies to prion protein gives positive staining of these cases, albeit the pattern of immunostaining differs from that seen in typical forms. Accumulation of prion protein is a molecular hallmark of prion diseases, and thus a reproducible, speedy and cost-efficient immunocytochemical screening of unusual dementias may help to establish the true incidence of prion diseases.

Adult↗
PubMed1992

Familial Alzheimer's disease with the amyloid precursor protein position 717 mutation and sporadic Alzheimer's disease have the same cytoskeletal pathology.

The cytoskeletal pathology of a patient with familial Alzheimer's disease (AD) associated with the probably causal amyloid precursor protein (APP) codon 717 Val----Ile mutation is described. In addition to moderately extensive beta A4 protein deposition within the substance of the brain and in blood vessel walls (congophilic angiopathy), there was abundant cytoskeletal pathology in the form of neurofibrillary tangles, plaque neurites and neuropil threads. Interestingly, plentiful cortical and subcortical Lewy bodies were also seen. In order to compare the cytoskeletal pathology in this case with that seen in sporadic cases of AD we (1) studied the immunohistochemical profile of the amyloid and cytoskeletal pathology with antibodies to beta A4 protein, tau, phosphorylated neurofilament epitopes and ubiquitin and (2) performed a biochemical fractionation and Western blot analysis for the abnormally phosphorylated form of tau (A68) characteristically seen in AD. No substantial difference between the familial case and sporadic cases could be found. We conclude that it is now reasonable to hypothesise that an abnormality in APP metabolism is responsible not only for the deposition of beta A4 protein, but also for the range of cytoskeletal pathology, typical of AD.

Alzheimer Disease↗
PubMed1992

Beta A4 deposition in the temporal cortex of adults with Down's syndrome.

The deposition of beta A4 has been quantified in the temporal cortex of 9 adults (4 male, 5 female) with Down's syndrome (DS), mean age (+/- SD) 54.7 +/- 8.8 years (range 41-67 years) at the time of death. Immunostaining with antibodies, raised to different portions of the beta A4 protein, showed a greater number of deposits than were seen with traditional silver impregnation or amyloid stains. Antibody to beta A4(1-10) identified fewer plaques than the antibody to beta A4(12-28), the mean ratio of beta A4(1-10)/beta A4(12-28) plaques being 0.30 +/- 0.10 (mean +/- SD). Morphologically, 'diffuse' and 'neuritic' deposits could be distinguished but there was no significant difference in the beta A4(1-10)/beta A4(12-28) ratio according to plaque morphology, nor did the ratio change with age. Quantitatively, the beta A4(12-28) load in the temporal cortex of DS patients was high, occupying some 14% of the field area, and it was not related to the age of the subject over the range studied. Similarly, the total beta A4(12-28) plaque count was high and not age-related. The proportion of morphological plaque types visualised by the Glees and Marsland silver impregnation and by beta A4(12-28) immunostaining were compared. In both techniques 'diffuse' plaques (D) were predominant in the younger subjects and the proportion of 'neuritic' plaques (N) increased with age. The relative proportions of cored plaques (Cp) and plaque cores (C) did not change significantly with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Astrocytosis, beta A4-protein deposition and paired helical filament formation in Alzheimer's disease.

Alzheimer's disease (AD) temporal cortex (Brodmann area 22) was investigated using stains for astrocytes (GFAP immunohistochemistry), paired helical filaments (Gallyas silver impregnation) and beta A4-protein deposition (beta A4-protein immunohistochemistry). Paired helical filament formation (PHF), as demonstrated by neurofibrillary tangle (NFT) and neuritic plaque (NP) density, was greatest in the pyramidal cell layers III and V. beta A4-protein deposition was greatest in layer III but was present in all neocortical layers. In a regression analysis, astrocyte density was significantly correlated with beta A4-protein deposition (R2 = 0.35, P = 0.02). Astrocyte density was also positively correlated with PHF formation as measured by NFT (R2 = 0.16, P = 0.14) and NP (R2 = 0.25, P = 0.06) density, but this was less significant. This quantitative study demonstrates that both beta A4-protein deposits and PHF formation are positively correlated with the severity of astrocytosis and that damage to the brain parenchyma in temporal cortex in AD may be slightly more strongly associated with beta A4-protein deposition than paired helical filament formation. These results demonstrate the close association of astrocytes with beta A4-protein deposition and neuritic change in AD.

Aged↗
PubMed1992

Accumulation of tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy.

In 8 brains of patients with various combinations of striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome, inclusion bodies were demonstrated in the cytoplasm and nucleus of both neuronal and oligodendroglial cells and in neuronal processes by means of silver staining, immunocytochemistry and electron microscopy. Differing from oligodendroglial cytoplasmic inclusions recognized by anti-ubiquitin, anti-alpha- and anti-beta-tubulin, and anti-tau antibodies, neuronal cytoplasmic inclusions were stained only by anti-ubiquitin antibody but not with those raised against cytoskeletal proteins. Tubular structures forming the inclusion bodies irrespective of their glial or neuronal location, have fuzzy cover and side extensions which make them similar to the linear structures described in motor neuron diseases. Our study proves that the accumulation of abnormal tubular structures in both oligodendrocytes and neurons is the basic pathological alteration in multiple system atrophy and defines multiple system atrophy as a group of diseases with similar cellular pathology or as a nosological entity.

Atrophy↗
PubMed1992

From slow virus to prion: a review of transmissible spongiform encephalopathies.

Spongiform encephalopathies include seven neurodegenerative diseases: three in man (Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease and kuru) and four in animals (scrapie, mink encephalopathy, bovine spongiform encephalopathy and chronic wasting disease in deer and elks). They are all transmissible to a variety of species, and man-to-man propagation of the diseases in the form of iatrogenic transmission has been well-documented. The infectious agent is highly unusual and the pathogenesis of infection remains controversial. The term prion was introduced to describe the proteinaceous infectious agent. Purification of this agent yielded a unique sialoglycoprotein, associated with the neuronal cell membrane, which is all or part of the infectious agent. Molecular genetics revealed variations in the prion protein; these are linked to or associated with the inherited forms of spongiform encephalopathies: familial Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease. The histological triad of spongiform change, neuronal loss and astrocytosis dominate the histological picture of spongiform encephalopathies. A recent case which did not develop any of the histological hallmarks of disease, but did have genetic abnormalities typical of the disease, indicates that the true incidence of Creutzfeldt-Jakob disease may be considerably higher than previously accepted, and a combination of molecular screening and immunohistochemistry for prion protein should complement traditional neuropathology to establish the diagnosis. The descriptive term of spongiform encephalopathy may now have to be abandoned in favour of prion disease.

Animals↗
PubMed1992

The St. George's dementia bed investigation study: a comparison of clinical and pathological diagnosis.

Sixty-four elderly patients who had been admitted to the St. George's Hospital Alzheimer's disease evaluation project during 1981-1989 were followed up to postmortem examination. Comparison between clinical diagnoses and neuropathological diagnoses indicated positive predictive values for the antemortem diagnoses of 50-67%. Existing clinical criteria may not be accurate enough to permit firm antemortem diagnosis of older people for either research or clinical purposes.

Aged↗
PubMed1991

Survival and distribution of transplanted human IMR-32 neuroblastoma cells.

The visualisation of transplanted cell lines is essential to determine both their viability and possible functional properties. Fluorescent latex microspheres were used to label cultured human neuroblastoma IMR-32 cells prior to transplantation. IMR-32 cells were first rendered amitotic by treatment with mitomycin C and bromodeoxyuridine and subsequently incubated with fluorescent microspheres for 3 days. Cell suspensions were prepared from these cultures and transplanted into the cortex and hippocampus of male Sprague-Dawley rats bearing ibotenate lesions of forebrain cholinergic projections. The animals were perfused at 4, 8 and 12 weeks post-transplantation and tissue was prepared for electron and light microscopy. IMR-32 cells containing fluorescent microspheres were clearly visualised in cryostat sections at all time points. Greater survival was seen in the hippocampus, with evidence of migration of cells from the site of implantation. Macrophages were seen at the electron and light microscope level, and were distinct from the discrete fluorescent labelled IMR-32 cells. Ultrastructurally, transplanted IMR-32 cells resembled cells in vitro, with microspheres clearly distinguished within the cytoplasm. Fluorescent microspheres provide a simple and direct labelling technique suitable for long-term transplant experiments using characterised cell lines.

Animals↗
PubMed1991

beta-Amyloid protein load is relatively uniform throughout neocortex and hippocampus in elderly Alzheimer's disease patients.

beta-Amyloid protein immunoreactivity in neocortex and hippocampus of Alzheimer's disease and control brains has been measured using an automatic image analysis system. Successive fields from the pial surface to white matter in 4 neocortical sites, parahippocampal gyrus and along the pyramidal cell layer in the hippocampus have been measured using a number of variables including: area fraction or load, counts per unit area and deposit size. In Alzheimer's disease beta-amyloid protein load in neocortex and hippocampus was significantly greater than in non-demented age-matched controls. beta-Amyloid protein load, as measured by size variables, was relatively uniform throughout the neocortex in elderly Alzheimer's disease patients. However, greater variability in deposition was measured in parahippocampal gyrus and hippocampus than in neocortex. Size and density variables used to measure beta-amyloid protein deposition were not correlated with age although there was a tendency for the cortical load to decrease with age beyond 80 years.

Aged↗
PubMed1991

Neuronal loss in the frontal cortex in HIV infection.

In an attempt to elucidate the cause and mechanism of the dementia and other neurological disorders that can occur in HIV-1 infection, we have quantitatively assessed neuronal populations, by means of a stereological technique (the disector), in the frontal cortex of patients with HIV infection. Eleven of sixty-five brains in the Medical Research Council Central AIDS Brain Bank were selected for study. The selected patients died without opportunistic infection or neoplasm affecting the brain; they had HIV encephalitis or minimal changes. We compared their neuronal counts with those of eight control subjects (seven died of systemic illness, one of pontine haemorrhage which did not affect the cerebral hemispheres). The neuronal numerical density was significantly lower in the HIV group than in the control group (mean [SD] 307 [46] vs 499 [113] x 10(2) per mm3; p less than 0.001). This difference represents a loss of about 38%. There was no significant difference between the HIV subgroups, which suggests that neuronal loss occurs in cases of minor pathology as well as in HIV encephalitis. This finding contributes to the understanding of dementia in AIDS patients and has important implications for their future treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1991

The effects of cholinergic drugs and cholinergic-rich foetal neural transplants on alcohol-induced deficits in radial maze performance in rats.

Chronic alcohol (20% v/v in drinking water for 28 weeks) impaired acquisition of radial maze spatial and associative tasks by increasing both within-trial working and long-term reference memory errors; animals with high (above the median of 100 mg/100 ml) blood alcohol concentrations (BACs) during treatment were significantly more impaired than those with BACs below the median. Alcohol-treated rats showed improvements in radial maze performance after treatment with cholinergic agonists (arecoline and nicotine) and disruption with antagonists (scopolamine and mecamylamine) at low doses which did not affect controls. These effects were more pronounced for working than reference memory, and not manifest with the peripherally acting antagonists hexamethonium and N-methylscopolamine. Transplants into cortex and hippocampus of cholinergic-rich basal forebrain (BF) and ventral mesencephalon (VM) foetal neural tissue improved radial maze performance of alcohol-treated rats to control level over a period of 9-12 weeks after grafting. Cholinergic-poor foetal hippocampal (HC) grafts were without effect. BF and VM, but not HC, grafts showed dense acetylcholinesterase (AChE) staining, tyrosine-hydroxylase staining was most pronounced in VM sections and dopamine-beta-hydroxylase staining was minimal in all grafts. Choline acetyltransferase (ChAT) activity was significantly reduced in cortex and hippocampus of alcohol-treated rats, except those given cholinergic-rich transplants. Alcohol treatment also significantly reduced AChE-positive cell counts in the nucleus basalis, medial septal and diagonal band brain areas, at the sources of the forebrain cholinergic projection system (FCPS). Cortical levels of noradrenaline were significantly reduced in all alcohol-treated rats, regardless of transplant, whereas cortical dopamine content was significantly elevated in all rats receiving transplants, regardless of behavioural effect, but not in alcohol-treated controls. Forebrain serotonin levels were not significantly altered by grafting or alcohol treatment. These results suggest that damage to the FCPS, as shown by reduced ChAT activity in target areas, and reduced AChE cell counts in projection areas, played an important part in the radial maze deficits displayed by alcohol-treated rats, since these animals were sensitive to cholinergic drug challenge, and cholinergic-rich transplants from two different sites in foetal brain elevated ChAT activity and restored cognitive function. In contrast alcohol- or graft-induced alterations in other transmitter systems did not correlate with the pattern of behavioural deficit and recovery.

Acetylcholine↗
PubMed1991

Isolation and characterisation of proliferating cells from the telencephalic vesicles of gestational-day 13 rats.

A method of isolating in culture a specific subpopulation of cells in the "S" phase of the mitotic cycle, from embryonic forebrain, is described. Different enzyme treatment and different substratum pretreatment are compared quantitatively to ensure optimal yield. These cells, isolated from the telencephalic vesicles of embryonic day (E) 13 rat embryos, were maintained in culture and their morphological and immunocytochemical characteristics were investigated at one and eight days in vitro.

Animals↗
PubMed1991

Effects of cholinergic-rich neural grafts on radial maze performance of rats after excitotoxic lesions of the forebrain cholinergic projection system--I. Amelioration of cognitive deficits by transplants into cortex and hippocampus but not into basal forebrain.

After ibotenate (10.0 mg/ml) lesions to the nucleus basalis and medial septal regions, at the source of the cortical and hippocampal branches of the forebrain cholinergic projection system, rats displayed long-lasting stable impairment in reference and working memory in both spatial (place) and associative (cue) radial maze tasks. Cell suspension transplants of cholinergic-rich fetal basal forebrain tissue dissected at embryonic day 15 substantially improved all aspects of radial maze performance to a comparable degree whether sited in cortex, hippocampus, or both regions of the host brain. No additive effects were obtained with grafts in both terminal regions, but total graft volume, assessed stereologically, showed a significant negative correlation with error scores. Rats with behaviourally effective grafts, like controls, were disrupted in the place task when tested in dim light which obscured extra-maze spatial cues. Lesioned rats were not affected by change in lighting. Grafts of cholinergic-poor fetal hippocampal tissue did not improve radial maze performance; neither did grafts of cholinergic-rich tissue placed within the host basal forebrain lesion sites. In rats with cholinergic-rich terminal grafts, cortical and hippocampal choline acetyltransferase activity was restored to control level, commensurate with site of transplant, whereas it was significantly reduced in lesioned animals and those with functionally ineffective grafts. The indiscriminate error pattern and insensitivity to changes in lighting shown by lesioned rats suggested that lesioning primarily disrupted attention rather than short- or long-term spatial or associative memory processes. Since rats with cholinergic-rich grafts showed both reduced errors and recovery of stimulus control, the data indicated that grafts affected information processing, rather than changes in motor or motivational processes. Changes in choline acetyltransferase activity and the behavioural efficacy of cholinergic-rich grafts are consistent with the involvement of acetylcholine in the behavioural deficits and recovery displayed by lesioned and grafted groups, but do not rule out contributions from other factors. The equipotency of grafts within each terminal region suggests also that there may be a considerable degree of functional cooperation between the two branches of the forebrain cholinergic projection system. Functional recovery may involve local, nonspecific synaptic or paracrine mechanisms within the target regions, since grafts were efficacious only when placed in the terminal areas, but not when sited homotopically in the basal forebrain, indicating that they did not achieve any functionally significant structural repair to the host brain at that site.

Acetylcholine↗
PubMed1991

Effects of cholinergic-rich neural grafts on radial maze performance of rats after excitotoxic lesions of the forebrain cholinergic projection system--II. Cholinergic drugs as probes to investigate lesion-induced deficits and transplant-induced functional recovery.

The effects of two doses of muscarinic (arecoline and scopolamine) and nicotinic (nicotine and mecamylamine) cholinergic receptor agonists and antagonists on the radial maze errors of rats, performing poorly after ibotenate lesions to the nucleus basalis and medial septal brain regions, were assessed before and after transplantation of cholinergic-rich and -poor fetal grafts, using tasks which measured short- (working) and long-term (reference) spatial and associative memory. Lesioned rats showed improvement with the agonists, and impairment with the antagonists, at low doses which did not affect the performance of controls; these effects were more marked for working than reference memory, especially in the spatial task. The peripherally acting antagonists N-methylscopolamine and hexamethonium did not affect the performance of control or lesioned rats. Effects of the cholinergic probes were re-examined 16 weeks after grafting, in groups with cholinergic-rich grafts to cortex and/or hippocampus which showed functional recovery, and groups with cholinergic-rich grafts to basal forebrain, or cholinergic-poor grafts to basal forebrain, cortex, and hippocampus, which showed no improvement. All lesioned rats, regardless of site, type, or efficacy of transplant, continued to show marked impairment with the antagonists. Poorly performing grafted animals also showed improvement with the agonists. In rats with behaviourally effective cholinergic-rich grafts, arecoline had no effect, but nicotine substantially increased working and reference memory errors, particularly spatial working memory errors. Rats with grafts in both cortex and hippocampus showed the largest increases in errors after nicotine. These results show that lesioned rats were more sensitive to the bi-directional effects of cholinergic receptor ligands than controls, consistent with a role for acetylcholine in the lesion-induced deficits. The predominant effect of drugs on working memory may also be consistent with disruption of acquisition rather than of storage or retrieval processes in memory, and may be related to impairment of attention. The results further show that, despite behavioural recovery, supersensitive responses to cholinergic drugs were not normalized in rats with cholinergic-rich grafts, and that an additive interaction between graft and host may have occurred in response to nicotine.

Acetylcholine↗
PubMed1991

Distribution and fine structural analysis of undifferentiated cells in the primate subependymal layer.

The subependymal layer (SEL) of the postnatal marmoset, a simian primate, has been investigated by histological and electron microscopic techniques. Although well documented in rodents, little is known about this layer in primates. The distribution of the SEL in marmosets is most extensive at birth around the anterior lateral ventricles, where the layer is generally 5-10 cells deep; however, there is considerable regional variation. With age the size of the SEL decreases dramatically, becoming very poorly demarcated in adult animals. Ultrastructurally, many subependymal cells in neonatal and young brains display the features of undifferentiated cells, although neurons and glia are also present. Cells displaying features intermediate between astrocytes and undifferentiated SEL cells are occasionally encountered. In adults undifferentiated cells are seen rarely and the former SEL is composed primarily of glial and neuronal processes. Thus the layer in primates probably represents a site of continued cellular differentiation in the postnatal brain and as such must play an important role in the final stages of cortical development.

Aging↗
PubMed1990

Cell proliferation in the subependymal layer of the postnatal marmoset, Callithrix jacchus.

Cells of the subependymal layer (SEL) have been shown to be capable of continued postnatal cell division throughout life in rodents. To determine if the primate brain behaves similarly, proliferative activity in the SEL of the marmoset has been investigated by tritiated thymidine autoradiography and bromodeoxyuridine immunocytochemistry. Both methods revealed the presence of DNA-synthesizing cells at all postnatal ages studied. The labelling index (LI), low at birth, reached a peak of almost 4% at one month but decreased gradually thereafter. In animals older than two years the LI was extremely low and labelled cells were rarely seen anywhere in the brain. The cell density of the SEL, in contrast to the low LI, was highest in neonates and decreased linearly with increasing age. Bromodeoxyuridine immunoreactivity revealed the distribution of proliferating cells in the SEL and neighbouring regions. Such cells were most abundant around the anterior lateral ventricle where the SEL was most evident. Proliferating cells were numerous in neonates, though not adjacent to the ependyma where counts for the LI were made, and were mainly located dorsally and ventrally at the junctions of the corpus callosum and caudate nucleus.

Aging↗