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Biomedical subjects

O Bugiani

Publications and source records attributed to O Bugiani.

At least 91 records · Page 5Linked to original sources
PubMed1991

Alzheimer patients: preamyloid deposits are immunoreactive with antibodies to extracellular domains of the amyloid precursor protein.

In patients with Alzheimer's disease, in patients with Down's syndrome and in aged non-demented individuals, anti-beta-protein antibodies label not only the fibrillary amyloid, but also preamyloid deposits. The latter are made up of amorphous material lacking the tinctorial, optical and ultrastructural properties of amyloid fibrils. To investigate the antigenic profile of preamyloid deposits, we have carried out an immunohistochemical study on specimens of cerebral cortex from 4 Alzheimer patients and two non-demented individuals, using antibodies to the beta-protein (anti-SP28), the C-terminal region of the amyloid precursor protein (APP) (anti-SP20) and an APP extracellular epitope between residues 50 and 100 (anti-preA4). Anti-preA4 and anti-SP28 immunoreactivity was found to be present in preamyloid deposits, whereas anti-SP20 immunoreactivity was not. These findings suggest that an extracellular portion of APP, close to the N-terminus of the molecule, participates with beta-protein in the composition of preamyloid deposits.

Aged↗
PubMed1991

Amyloid protein of Gerstmann-Sträussler-Scheinker disease (Indiana kindred) is an 11 kd fragment of prion protein with an N-terminal glycine at codon 58.

Gerstmann-Sträussler-Scheinker (GSS) disease is a familial neurological disorder pathologically characterized by amyloid deposition in the cerebrum and cerebellum. The GSS amyloid is immunoreactive to antisera raised against the hamster prion protein (PrP) 27-30. This is a proteinase K-resistant glycoprotein of 27-30 kd that is derived from an abnormal isoform of a neuronal glycoprotein of 33-35 kd designated PrPSc and is a molecular marker of amyloid fibrils isolated from animals with scrapie and humans with related disorders. We have purified and characterized proteins extracted from amyloid plaque cores isolated from two patients of the Indiana kindred of GSS disease. We found that the major component of GSS amyloid is an 11 kd degradation product of PrP, whose N-terminus corresponds to the glycine residue at position 58 of the amino acid sequence deduced from the human PrP cDNA. In addition, amyloid fractions contained larger PrP fragments with apparently intact N-termini and amyloid P component. These findings suggest that the disease process leads to proteolytic cleavage of PrP, generating an amyloidogenic peptide that polymerizes into insoluble fibrils. The N-terminal cleavage of PrP in GSS disease occurs at a tryptophan-glycine peptide bond identical to that cleaved by proteinase K in vitro to generate PrP 27-30 from hamster PrPSc at codon 90. Since no mutations of the structural PrP gene have been found in the Indiana family of GSS disease, it is conceivable that factors other than the primary structure of PrP play a crucial role in the process of amyloid formation and the development of clinical neurologic dysfunction.

Amino Acid Sequence↗
PubMed1991

Desferrioxamine infusion can modify EEG tracing in haemodialysed patients.

Neurological derangement has been reported in haemodialysed patients receiving intravenous desferrioxamine (DFO) for aluminium-related disorders. The possible direct effects of desferrioxamine on EEG recordings were investigated in ten haemodialysed patients who underwent a DFO test 2 h after the end of dialysis. According to a commonly accepted protocol, 40 mg/kg body-weight of desferrioxamine was infused in 60 min. EEG recording was continuously performed, starting 30 min before and stopping 30 min after the desferrioxamine infusion. Besides visual inspection, EEG records were digitised, tapered, and spectrally analysed with Digital PDP 11/73 microcomputer. Basal EEG recording was normal in all patients. In three patients a progressive EEG slowing was detected by visual inspection during desferrioxamine infusion; in these cases automatic analysis revealed a 50% increase in power of slower frequencies 30 min after starting the infusion, when no changes in plasma aluminium concentrations are detected; a complete recovery was observed 30 min after desferrioxamine withdrawal. In one patient bilateral paroxysms of slow waves appeared, so we stopped desferrioxamine infusion. Two of the three patients who developed EEG abnormalities also had an increased aluminium body burden (positive DFO test). Results indicated that desferrioxamine per se can modify EEG in haemodialysis patients and that its effect is not mediated by acute increases of plasma aluminium concentrations. The finding of a positive DFO test in two of three patients with EEG changes may suggest that an aluminium-induced blood-brain barrier derangement could have played a role. However, prompt recovery after ceasing desferrioxamine infusion strongly suggests a direct role of desferrioxamine in the induction of EEG changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1990

Alzheimer patients and Down patients: abnormal presynaptic terminals are related to cerebral preamyloid deposits.

In Alzheimer's disease, in Down syndrome and in normal aging, scattered deposits of amyloid fibril precursors occur in both cerebral cortex and subcortical grey structures. Within such preamyloid deposits, no degenerating neurites with paired helical filaments have ever been observed. This study, carried out on brains from Alzheimer patients and Down patients, reports on the relationship between preamyloid deposits and neuritic changes. These changes were represented by presynaptic terminal swellings immunolabeled by antisynaptophysin and antiubiquitin antibodies, not by Alz50. These findings support the view that the deposition of amyloid fibril precursors in the neuropil is closely related to presynaptic terminals, although whether the former precedes or follows the development of presynaptic terminal changes is still undetermined.

Adult↗
PubMed1990

Neurofibrillary tangles of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease share antigenic determinants with those of Alzheimer disease.

In the Indiana kindred of Gerstmann-Sträussler-Scheinker disease, neurofibrillary tangles (NFT) with paired helical filaments (PHF) are numerous, widespread and consistently present in the cerebral cortex and several subcortical nuclei. Such tangles share antigenic determinants with those of Alzheimer disease; in fact, they are recognized by Alz50, anti-PHF and anti-ubiquitin antibodies. Thus, NFT with structural and immunocytochemical similarities are present in two distinct forms of amyloidosis of the central nervous system, i.e. the Indiana kindred of Gerstmann-Sträussler-Scheinker disease and Alzheimer disease.

Aged↗
PubMed1990

Cerebral preamyloid deposits and congophilic angiopathy in aged dogs.

The brains of 7 dogs aged 6 to 18 years have been histochemically and immunohistochemically investigated at the light- and electron microscopy levels for preamyloid deposits and amyloid fibrils to verify the hypothesis that the accumulation of cleavage products of amyloid precursor protein is related not only to Alzheimer's disease but also to the normal aging of the brain. Preamyloid deposits were detected in the neuropil of the cerebral cortex and neostriatum, whereas amyloid fibrils were found in the walls of parenchimal and leptomeningeal vessels. The densities of preamyloid deposits in the neuropil and of deposits of amyloid fibrils in the vessel walls were higher in the brains of the most aged dogs. These findings suggest that aging of the canine brain is characterized by an accumulation of intermediate cleavage products of the amyloid precursor protein in both the neuropil and the vessel walls, and by processing of these products to amyloid fibrils in the vessel walls.

Aging↗
PubMed1990

Coexistence of Alzheimer's amyloid precursor protein and amyloid protein in cerebral vessel walls.

Polyclonal antibodies to synthetic peptides homologous to amino acid residues 45-62, 597-624, and 676-695 of the predicted sequence of Alzheimer's amyloid precursor protein (APP) were used to investigate the site of origin of APP, and the relationship between APP and amyloid protein in Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D). Cortical sections as well as homogenates of isolated leptomeningeal and cortical microvessels from three patients with AD, two patients with HCHWA-D, and two nondemented controls were probed. In vessel extracts of both groups of patients and the controls, APP was detected as a set of proteins with electrophoretic mobility of 105 to 135 kilodaltons. In cortical sections of all subjects, APP immunoreactivity was found in leptomeningeal and cortical vessel walls. In patients with AD and HCHWA-D, APP and amyloid fibrils coexisted in the same vessels. Moreover, APP immunoreactivity was found in association with 50% of senile plaques in AD brains, but was not evidenced in parenchymal amyloid deposits in patients with HCHWA-D. These data suggest that the vascular system is a source of APP and that the processing of APP into insoluble fibrils in AD and HCHWA-D may take place in situ.

Aged↗
PubMed1989

Alzheimer patients and Down patients: cerebral preamyloid deposits differ ultrastructurally and histochemically from the amyloid of senile plaques.

The preamyloid deposits found in the cerebral grey matter of Alzheimer patients and Down patients following immunostaining with anti-beta-protein antisera are neither birefringent following Congo red staining nor fluorescent after thioflavine S treatment. Further, they contain small amounts of alpha 1-antichymotrypsin, sulfated glycosaminoglycans and complement fraction C3d, but not the P component. As suggested previously, the material accumulated in these deposits may lack the molecular conformation responsible for the properties of amyloid fibrils. To test this hypothesis, we selected cortical samples from 6 Alzheimer and 4 Down patients for an electronmicroscopical study of senile plaques and of preamyloid deposits, both identified by indirect immunogold staining with anti-beta-protein antiserum. We observed the labelling of 4-8 nm wide amyloid fibrils in the plaque cores and of extracellular electrondense, flaky and irregularly distributed material in the preamyloid deposits. In the latter, amyloid fibrils were very rarely detected. These findings support the view that preamyloid deposits mostly contain amyloid precursors that are not yet organized in fibrils.

Alzheimer Disease↗
PubMed1989

Alzheimer patients: preamyloid deposits are more widely distributed than senile plaques throughout the central nervous system.

In Alzheimer's disease, anti-beta-protein antisera label not only amyloid deposits accompanied by degenerating neurites (neuritic and mature plaques) and amyloid deposits without degenerating neurites, but also preamyloid deposits lacking the optical properties of amyloid fibrils. We have carried out a study of the brains of 13 patients with Alzheimer's disease (one with the familial and 12 with the sporadic form), using anti-beta-protein and anti-paired helical filament antisera, thioflavine S, Congo red and Gallyas' silver impregnation, in order to determine whether the distribution of preamyloid deposits and amyloid deposits without degenerating neurites differs from that of amyloid deposits with degenerating neurites. Preamyloid deposits and amyloid deposits with or without degenerating neurites were present in cortex, neostriatum, medial geniculate body and thalamic (anterior and extralaminar) nuclei, whereas preamyloid deposits and amyloid deposits without degenerating neurites, but not amyloid deposits with degenerating neurites, were present in other thalamic nuclei, in the globus pallidus, brainstem, cerebellar cortex and upper spinal cord. These results support the view that preamyloid deposits evolve to senile (neuritic and mature) plaques only in specific brain regions, where neurites vulnerable to amyloid fibrils are widely distributed.

Adult↗
PubMed1989

Down patients: extracellular preamyloid deposits precede neuritic degeneration and senile plaques.

Using anti-SP28 (a polyclonal antibody to a 28 residue synthetic peptide homologous to the NH2-terminal region of the Alzheimer amyloid beta-protein) to investigate the cerebral cortex of 6 Down patients aged 6-55 y, we found that, besides senile plaques and congophilic vessels, extracellular deposits unrelated to degenerating neurites, tangle-bearing neurons or congophilic vessels were labelled. These deposits were similar to the extracellular deposits previously observed in the cerebral cortex of Alzheimer patients and non-demented individuals. The material accumulated in the deposits did not react with Congo red, thioflavine S or, on some occasions, silver salts and therefore might have been constituted by beta-protein precursors lacking the molecular conformation of amyloid fibrils. Age-related analysis of the cortical lesions in Down patients suggested that such extracellular deposits precede degenerating neurites and evolve into senile plaques.

Adult↗
PubMed1989

Cerebral extracellular preamyloid deposits in Alzheimer's disease, Down syndrome and nondemented elderly individuals.

Using anti-SP28 (a polyclonal antibody to a 28 residue synthetic peptide homologous to the NH2-terminal region of Alzheimer amyloid beta-protein) to investigate the cerebral cortex of 8 Alzheimer and 6 Down patients and 13 nondemented individuals, we found that, besides senile plaques and congophilic vessels, extracellular deposits unrelated to degenerating neurites, tangle-bearing neurons or congophilic vessels were labelled. These deposits were observed in all Alzheimer and 4 Down patients, and in 5 nondemented individuals. The material accumulated in these deposits did not react with Congo red, thioflavine S or, on some occasions, silver salts and therefore might have been constituted by beta-protein and/or beta-protein precursors lacking the conformation of amyloid fibrils.

Aged↗
PubMed1988

Preamyloid deposits in the cerebral cortex of patients with Alzheimer's disease and nondemented individuals.

A polyclonal antibody to a 28 residue synthetic peptide, homologous to the NH2 terminal region of amyloid beta-protein, was employed in a study of the frontal and temporal cortex of 8 Alzheimer patients and 13 non-demented individuals aimed to define the relationship of immunolabelled to argyrophilic, congophilic and thioflavine S-positive cortical lesions. In Alzheimer patients, this antiserum labelled not only senile plaques and congophilic angiopathy, but also cortical deposits that were neither argyrophilic, congophilic nor thioflavine S-positive and were unrelated to degenerating neurites, tangle-bearing neurons or congophilic angiopathy. Similar lesions were observed in 4 of 13 non-demented individuals, in the absence of tangles, plaques or congophilic angiopathy, and in one in association with plaques. Such deposits might have been due to amyloid precursors still lacking the beta-pleated sheet molecular conformation responsible for amyloid tinctorial and optical properties.

Adult↗
PubMed1988

Progressive supranuclear palsy with hypertrophy of the olives. An immunocytochemical study of the cytoskeleton of argyrophilic neurons.

In a patient with progressive supranuclear palsy (PSP) and hypertrophy of the olives, neurons with different forms of argyrophilic degeneration were detected by means of Bodian's silver staining method, i.e., neurofibrillary tangle-bearing neurons in the basal ganglia and brain stem, ballooned argyrophilic neurons in the brain stem, and hypertrophied neurons in the olives. In these cells, the cytoskeleton was investigated to ascertain whether neurons with different cytoskeletal changes contained phosphorylated neurofilaments (P-Nf) in the perikaryon. This study, carried out using two monoclonal antibodies that recognize phosphorylated epitopes of the neurofilament high molecular weight subunits, showed that hypertrophied olivary neurons, most ballooned neurons and a small aliquot of tangle-bearing neurons were labelled. The immunostaining of hypertrophied and ballooned neurons was localized in the whole perikaryon and dendrites, whereas that of tangle-bearing neurons was confined to the tangle. These findings were reproduced in five additional patients (one with hypertrophy of the olives, four with PSP) and demonstrated that, in PSP, the mechanism responsible for tangle formation does not affect the ability of neurons to accumulate P-Nf. This fact suggested that perikaryonal P-Nf accumulation is likely to be part of the cell reaction to abnormal conditions affecting the neuronal cytoskeleton.

Brain↗
PubMed1987

Aluminum-induced decreases in choline acetyltransferase, tyrosine hydroxylase, and glutamate decarboxylase in selected regions of rabbit brain.

The neuropathological and neurochemical effects of intracisternally administered aluminum-powder suspensions were studied in adult rabbits. The right half of each brain was fixed for neuropathological examination, and neurotransmitter-synthesizing enzyme activities were measured in homogenates of structures dissected from the left half of each brain. The neuropathological changes associated with aluminum-induced encephalomyelopathy, including neurofibrillary degeneration, were observed in several regions of the central nervous system of the aluminum-treated rabbits. The striatum was consistently free of changes. Decreases in choline acetyltransferase and tyrosine hydroxylase activities of more than 30% were observed in the striatum of animals within 14-21 d and at longer times after aluminum injection. The decrease in striatal choline acetyltransferase activity appears to be unrelated to pathological changes in the striatal cholinergic neurons. The decrease in tyrosine hydroxylase activity in the striatum may be unrelated to neuropathological changes in dopaminergic cell bodies in the midbrain. Significant decreases in glutamate decarboxylase activity in the cerebellum may be related to cell losses in this region, whereas choline acetyltransferase activity deficits in the whole hippocampus remain unexplained.

Aluminum↗
PubMed1985

Progressive dialytic encephalopathy and the problem of aluminum neurotoxicity.

Some clinical, epidemiological, and pathological aspects of the progressive dialytic encephalopathy have been considered with the aim to clarify the nature of the disease as well as to identify factors that possibly favor the neurotoxic effect of aluminum in uremic patients. The role of the blood-brain barrier has been outlined. The concept of a delayed neurotoxicity of aluminum has been introduced to face the problem of the risk of mental deterioration and neuromyopathies in patients on oral aluminum administration. A comparison has been made with the dementias of the Alzheimer type and with amyotrophic lateral sclerosis in which aluminum is regarded as a possible etiologic factor. Finally, a proposal has been made of monitoring aluminum levels in blood serum and cerebrospinal fluid as well as the results of electrodiagnostic tests, CT scan, and language and psychometric examinations, that may help in clarifying the problem of aluminum neurotoxicity in uremic patients.

Aluminum↗