Expression patterns of human PNS myelin proteins in neuropathies associated with anti-myelin antibodies.
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Biomedical subjects
Publications and source records attributed to J Ulrich.
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A morphometric investigation has been carried out on the synaptic mitochondria of cerebellar glomeruli in young, adult and old rats by means of a computer-assisted image analysis technique. Mitochondrial volume density (Vv), numerical density (Nv), average volume (V) and average length (Skeleton = Sk) were investigated in tissue samples fixed, embedded and sectioned according to conventional electron microscopic methods. Vv was unchanged in the three groups of age taken into account. Nv was significantly increased in adult vs. young animals, whereas it was decreased in the old group as compared to both the other two groups investigated. V and Sk showed the same age-dependent changes: they significantly decreased in the adult vs. the young and the old groups of rats while increased significantly in the old rats vs. both the adult and young animals. A percentage distribution of Sk demonstrated that in the old group 20.6% of the population of synaptic mitochondria accounts for elongated organelles (> 5 microns) as compared to 8.6% and 5.3% in young and adult animals, respectively. The present findings match the changes previously reported by us on the ultrastructure of synaptic contact zones both in rats and human beings, and support the idea of an age-dependent dynamic adaptation in the morphology of synaptic mitochondria to cope with the metabolic needs of the pattern of synaptic connectivity they subserve.
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Nerve biopsies are useful for the etiological diagnosis of certain polyneuropathies. One of them is familial amyloidotic polyneuropathy, which can be diagnosed and specified on the basis of a Kongo-red stain and immunohistochemical analysis of the amyloid deposited in the nerve. This possibility is illustrated by a case report. A review of the various clinical, morphological and genetic aspects of these diseases is given.
To obtain an insight into the network of cytokine gene transcription in the brain tumour microenvironment, we investigated the expression of genes encoding for interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, interferon (IFN)-gamma, granulocyte-macrophage colony-stimulating factor, tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta 1, -beta 2 and -beta 3 in freshly excised brain tumour samples and autologous peripheral blood mononuclear cells. Tissue specimens from 15 primary brain tumours, three brain metastases, five meningiomas, autologous peripheral blood mononuclear cells (PBMC) and three brain tumour cell lines were tested by reverse polymerase chain reaction. Despite the presence of T-lymphocytes, cytokine gene transcripts typically detectable upon T cell receptor triggering could not be observed in central nervous system tumours of diverse histology. In primary brain neoplasms, transcription of genes encoding for the inhibitory cytokines TGF-beta and IL-10 was detectable in more than 50% of samples. IL-6 transcripts could only be detected in malignant gliomas. In brain metastases, virtually no cytokine gene transcripts could be observed. Surprisingly, TGF-beta transcripts were also detected in all meningiomas. Thus, transcription of genes encoding for inhibitory factors appears to prevail in primary brain neoplasms.
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To perform a quantitative investigation on synaptic ultrastructural features in the human hippocampus in normal old and senile demented patients we stained our tissue samples by means of the ethanol-phosphotungstic acid (E-PTA) preferential technique. In addition to the synaptic contact zones, we found that structures similar to neurofibrillary tangles (NFT) and senile plaques (SP) were remarkably positive to our staining procedure, while the background was faintly electron lucent. On the basis of the E-PTA staining properties and specificity, we support that the reactive sites of these positive structures are represented by basic amino acids. The recently demonstrated presence of 4 basic amino acids (1 arginine, 3 histidine) in the cleaved fragment of the amyloid precursor protein (APP) suggest us to hypothesise that this APP portion may represent the common constitutive element of the many morphologically different alterations found in the brains of senile demented patients.
Synaptic contact zones in the dentate gyrus supragranular layer and cerebellar glomeruli of autoptic samples from adult, old and demented patients have been investigated by means of computer-assisted morphometric techniques. In physiological aging and senile dementia, the synaptic average area was significantly increased as compared with adult values in both the CNS areas investigated. Conversely, the number of contacts and their total surface contact area per unit volume of tissue were decreased. In animal models, the enlarged contact zones are reported to undergo perforations and splitting to modify synaptic connectivity. As against these assumptions, the increased synaptic size observed in our study appears to represent a compensative reaction of old and demented CNS to counteract the decrease in number and total contact area of the synaptic junctions.
When processing data from the long-term follow-up of cardiovascular diseases in the Most district the author revealed: 1. In the course of 30 years the ratio of older subjects increased in the Most district (men above 60 years, women above 55 years) from 9.1% in 1961 to 17.3% in 1990; the ageing of the population in the Most district is more rapid than corresponds to average data from Czech Republic and the North Bohemian region. 2. In the course of 40 years (1950-1990) the rising trend of hospitalized morbidity on account of all cardiovascular diseases, ischaemic heart disease and myocardial infarction persists. 3. Analysis of the morbidity from cardiovascular diseases in 1989 in the Most district did not reveal any differences as compared with 1976. It was confirmed that the ratio of deaths from cardiovascular diseases rises with age. A limiting factor is also the necropsy rate, in particular as regards patients who did not die in hospital. Particularly alarming is the cardiovascular mortality in the group aged 40-69 years.
Aging of the brain involves not only appreciable shrinkage of the cortex and other gray matter structures but above all loss of white matter. This could be due to a decline in the number of myelinated fibers or to a loss of water. To assess the role played by each of these factors we studied brains from 33 neurologically intact subjects at autopsy representing three different age groups: 15-50, 51-70, and 71-93 years. The precentral gyrus, gyrus rectus, and corpus callosum were selected for investigation, with staining for alkaline phosphatase on native cryostat sections to visualize the capillary network, and staining for myelin on semithin sections for nerve fiber visualization. Atrophy was objectified by measuring the number of capillaries, the intercapillary distance, and capillary length, since the capillary network remains constant throughout normal life. A mean difference of 16-20% was found, representing white matter atrophy, between the oldest and youngest age-groups. The cortex of the corresponding gyri, on the other hand, showed a difference of less than 6%. Morphometric investigation of sections stained for myelin showed that the brains with a mean age of 78.7 +/- 6.6 years had 10-15% fewer myelinated fibers. This was only partly offset by an increase in the volume of extracellular space. Our findings show that the age-related decline in brain volume is much more a question of white matter atrophy than of brain cortex atrophy. White matter atrophy could be an indirect indicator of nerve cell loss, since the volume of a nerve cell is much smaller than its myelinated fiber.
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Mild acid hydrolysis of Escherichia coli O104 lipopolysaccharide released an O-specific polysaccharide, a tetrasaccharide repeating unit, the corresponding dimer, and a disaccharide fragment of the repeating unit. Complete and incomplete cores, and oligosaccharides comprising fragments of the repeating unit and the core region, were also obtained. On the basis of sugar and methylation analysis, FAB-mass spectrometry and NMR spectroscopy of the hydrolysis products, the repeating unit of the O-specific polysaccharide was shown to be the tetrasaccharide:-->4)-alpha-D-Galp-(1-->4)-alpha-Neup5,7,9Ac3++ +-(2-->3)-beta-D- Galp-(1-->3)-beta-D-GalpNAc (1-->. The linkage between the O-specific polysaccharide chain and the core region, which appeared to be of the R2 type, was established. These results indicate that N-acetylneuraminic acid, located in the O-specific polysaccharide, is an inherent lipopolysaccharide component.
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Specific, high-resolution techniques (quantitative enzyme radioautography and in situ hybridisation histochemistry) have revealed distribution, abundance and cellular localization of the isoenzymes MAO-A and MAO-B and their mRNAs in human post-mortem brainstem. Whereas MAO-A protein and mRNA are expressed by noradrenergic neurons of the locus coeruleus, MAO-B protein and mRNA are expressed by serotoninergic neurons of the raphé nuclei. In the substantia nigra, MAO-B was more abundant than MAO-A; the former was localized in the reticular zone and the latter in the compact zone (where melanin-containing dopaminergic neurons are found). To date, it has not been possible to detect mRNA for either MAO-A or MAO-B in the substantia nigra or in glial cells of the brain regions investigated, suggesting either that the technique has limited sensitivity, or the possible existence of MAO-A and MAO-B subtypes.
A quantitative investigation has been carried out on synaptic contact zones of dentate gyrus supragranular layer and cerebellar glomeruli in autoptic samples from adult, old and demented patients. During physiological aging and senile dementia, the synaptic average area was significantly increased as compared to adult values in both the CNS areas investigated. Conversely, the number of contacts and their total surface contact area per unit volume of tissue were decreased. Current literature reports that, in animal models, enlarged synapses undergo perforations and splitting to modify synaptic connectivity. As against these assumptions, the increased synaptic size observed in our study appears to represent a compensative reaction of old and demented CNS to counteract the reduction in number and in total contact area of the synaptic junctions.
A1 induces neurofibrillary tangles in the perikaryon of neurons in vivo and in culture. The effect of A1 ions complexed with maltol, a plant-derived ligand of A1, on purified neurofilament preparations was studied in vitro. The binding of A1 to the arm-like projections of the high (H)- and medium (M)-molecular-weight neurofilament subunits causes a conformational change of the molecule (intrafilamentous reaction), characterized by an altered migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In addition, A1 compounds strongly stimulate the interaction between neurofilaments (interfilamentous reaction). The possibility that phosphate groups of the H and M sidearms are involved in binding A1 ions is discussed with regard to the migration on SDS-PAGE of dephosphorylated neurofilaments incubated with A1 compounds and the alteration by A1 ions of neurofilament phosphorylation in vitro by the associated kinase. Immunoblotting analysis of neurofilaments in cultivated neurons intoxicated with A1 compounds revealed a similar A1-dependent alteration of the neurofilament subunit conformation. This result suggest that the mechanism of A1-induced bundling of neurofilaments derived from in vitro studies might be involved in the formation of tangles in situ.
Senile plaques in the cerebral neocortex, entorhinal cortex and hippocampus are reactive for Acetylcholinesterase (AChE). The same types of plaques are observed, as with immunostains for beta-protein, including the very simple ones, consisting nearly exclusively of loose deposits of beta-protein. If there are many plaques, the normal network of AChE-positive axons disappears. Explanations for both, the apparent shift of AChE from the axons to the plaques on the one hand and the very early development of AChE positive deposits during the plaque development on the other hand are sought.
This is a short biography of the Polish-Ukrainian-Israelian bacteriologist and science theoretician Ludwik Fleck, whose life was marked by wars, years of captivity in concentration camps and changes of nationality. His most important insight into the way in which scientific knowledge is gained was that knowledge is not the result of an individual process of a theoretical consciousness by itself, but the result of collective social activity.