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At least 343 records · Page 19Linked to original sources
PubMed1981

Progressive supranuclear palsy in the course of subclavian steal syndrome.

A 70-year-old man manifested during four years a progressive clinical picture consisting in palsy of gaze, axial rigidity, disorders of standing and gait, dysarthria, dysphagia. Neuroradiological investigations demonstrated proximal thrombosis of the left subclavian artery with subclavian steal. At necropsy, degenerative changes in several areas of the basal ganglia and brain stem, with presence of globose neurofibrillary tangles, were found, consistently with the pathologic pattern of the Progressive Supranuclear Palsy (PSP). The association of PSP and subclavian steal syndrome has not been previously reported, to our knowledge. We hypothesize that chronic ischemia, due to subclavian steal syndrome, in the vertebral basilar system and its watershed versus carotid system may have favoured the appearance, in these same areas, of the changes of the PSP.

Aged↗
PubMed1981

Melanosis cerebelli.

Melanosis cerebelli (melanic pigmentation involving the dentate nuclei and the granular layer of the cerebellar cortex) is described in three patients, aged between 72 and 99 years. In two cases atrophic changes of the Alzheimer type co-existed in the cerebral cortex. One patient had a history of tremors, possibly cerebellar in origin.

Aged↗
PubMed1975

Atypical progressive multifocal leukoencephalopathy with plasma-cell infiltrates.

In rare cases of progressive multifocal leukoencephalopathy (PML) the lesions are atypical in that the characteristic alteration of oligodendrocytic nuclei is infrequent or absent, and the demyelinated foci contain mononuclear inflammatory infiltrates including numerous plasma cells. Otherwise these cases, both as to the topographic features of the lesions, and the background of chronic lymphoproliferative or myeloproliferative disease or immunosuppressive treatment, conform to the usual pattern. In the case here reported, that of a 54-year-old man receiving immunosuppressive drugs for chronic polymyositis, electron microscopy showed papovavirions in astrocytic nuclei and fluorescent antibody studies indicated that these represented JC virus. In this and the 3 previously reported similar cases of atypical PML, the neurologic illness was less devastating than generally occurs in classic PML. Possibly these cases represent instances of unusually strong host-resistance against the disease.

Astrocytes↗
PubMed1998

Mechanisms of neurofibrillary degeneration and the formation of neurofibrillary tangles.

Alzheimer disease (AD) has polyetiology. Independent of the etiology the disease is characterized histopathologically by the intraneuronal accumulation of paired helical filaments (PHF), forming neurofibrillary tangles, neuropil threads and dystrophic neurites surrounding the extracellular deposits of beta-amyloid in plaques, the second major lesion. The clincal expression of AD correlates with the presence of neurofibrillary degeneration; beta-amyloid alone does not produce the disease clinically. Thus arresting neurofibrillary degeneration offers a promising key target for therapeutic intervention of AD. The major protein subunit of PHF is the microtubule-associated protein tau. Tau in AD brain, especially PHF, is abnormally hyperphosphorylated and glycosylated. With maturation, the tangles are increasingly ubiquitinated. Levels of tau and conjugated ubiquitin are elevated both in AD brain and CSF. The AD abnormally phosphorylated tau (AD P-tau) does not promote microtubule assembly, but on dephosphorylation its microtubule promoting activity is restored to approximately that of the normal tau. The AD P-tau competes with tubulin in binding to normal tau, MAP1 and MAP2 and inhibits their microtubule assembly promoting activities. Furthermore, the AD P-tau sequesters normal MAPs from microtubules. The association of AD P-tau with normal tau but not with MAP1 or MAP2 results in the formation of tangles of 3.3 +/- 0.5 mm filaments. Deglycosylation of Alzheimer neurofibrillary tangles with endoglycosidase F/N-glycosidase F untwists the PHF resulting in tangles of thin filaments similar to those formed by association between the AD P-tau and normal tau. Dephosphorylation or deglycosylation plus dephosphorylation but not deglycosylation alone restores the microtubule assembly promoting activity of tau. In vitro AD P-tau can be dephosphorylated by protein phosphatases PP-2B, PP-2A and PP-1 but not PP-2C and all the three tau phosphatases are present in brain neurons. Tau phosphatase activity is decreased by approximately 30% in AD brain. Inhibition of PP-2A and PP-1 activities in SY5Y neuroblastoma by 10 nM okadaic acid causes breakdown of microtubules and the degeneration of these cells. It is suggested (I) that a defect(s) in the protein phosphorylation/dephosphorylation system(s) leads to a hyperphosphorylation of tau, (ii) that this altered tau causes disassembly of microtubules and consequently a retrograde neuronal degeneration; (iii) a pharmacological approach to AD is to enhance the tau phosphatase activity; and (iv) that CSF tau and conjugated ubiquitin levels are promising markers of AD brain pathology.

Aged↗
PubMed2000

Mechanism of neurofibrillary degeneration and pharmacologic therapeutic approach.

Neurofibrillary degeneration is a key histopathological brain lesion of Alzheimer disease (AD) and related neurodegenerative disorders such as frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17), commonly referred to as tauopathies. Microtubule associated protein (MAP) tau, which is a major MAP of a normal mature neuron is abnormally hyperphosphorylated in tauopathies and is the major protein subunit of paired helical filaments (PHF)/straight filaments (SF) which accumulate in the soma (as neurofibrillary tangles) and dystrophic neurites (as neuropil threads and as dystrophic neurites surrounding the beta-amyloid core in neuritic plaques in AD) of the affected neurons. Unlike normal tau which stimulates assembly and stabilizes microtubules, the abnormally hyperphosphorylated tau inhibits assembly and disrupts microtubules. The abnormally hyperphosphorylated tau competes with tubulin/microtubules in associating with normal tau, MAP1 and MAP2. This sequestration of normal MAPs by the abnormal tau results in the breakdown of the microtubules. The association of the abnormal tau with normal tau and not with MAP1 or MAP2 results in the formation of tangles of tau filaments. All these toxic properties of the abnormally hyperphosphorylated tau are eliminated by its enzymatic dephosphorylation. Activities of phosphoseryl/phosphothreonyl protein phosphatases (PP)-2A and PP-1 which can dephosphorylate the abnormal tau to a normal-like state are compromised in AD brain. Dephosphorylation by PP-2A and PP-2B and to a lesser extent by PP-1 restores the normal microtubule assembly promoting activity in AD P-tau in vitro. Neurofibrillary tangles of PHF isolated from AD brain are also dissociated on in vitro dephosphorylation with PP-2A, and the tau released by this treatment can stimulate microtubule assembly. Thus, it appears that the abnormal hyperphosphorylation of tau leads to neurodegeneration through breakdown of the microtubule network and that the abnormal tau on association with normal tau forms neurofibrillary tangles of tau filaments i.e. PHF/SF. Increase in tau phosphatase activity is a promising approach to inhibit neurofibrillary degeneration and thereby the diseases characterized by this lesion.

Alzheimer Disease↗
PubMed1996

Traumatically induced axonal damage: evidence for enduring changes in axolemmal permeability with associated cytoskeletal change.

Recent studies have demonstrated that delayed or secondary axotomy is a consistent feature of traumatic brain injury in both animals and man. Moreover, these studies have shown that the pathogenesis of this secondary axotomy involves various forms of initiating pathology, with the suggestion that, in some cases, only the axonal cytoskeleton is perturbed, while, in other cases, both the axonal cytoskeleton and related axolemma manifest traumatically induced perturbations. In the current communication, we continue in our investigation of the significance of these traumatically induced alterations in axolemmal permeability and their relation to any related intra-axonal cytoskeletal change. This was accomplished in cats which received intrathecal infusions of peroxidase, an agent normally excluded by the intact axolemma. These animals were subjected to traumatic brain injury, and sites showing altered axolemmal permeability to the peroxidase were assessed at the light and electron microscopic level. Through this approach, we recognized that a traumatic episode of moderate severity evoked changes in axolemmal permeability which surprising endured for up to 5 hrs postinjury. At such focal sites of altered permeability, the related cytoskeleton showed a statistically significantly neurofilament compaction, with the strong suggestion of concomitant neurofilament sidearm loss, microtubular dispersion, and mitochondrial abnormality. Over time, these events led to further disorganization of the axonal cytoskeleton which translated into impaired axoplasmic transport and secondary axotomy. Most likely, these alterations in axolemmal permeability result in either the direct or indirect effects upon the axonal cytoskeleton that precipitate the damaging sequences resulting in delayed axotomy.

Animals↗
PubMed1983

Immunocytochemistry of brain-reactive monoclonal antibodies in peripheral tissues.

Among a total of 135 tissue-reactive monoclonal antibodies previously prepared, 81 were brain-selective and were classified into neuronal and non-neuronal categories. The neuronal antibodies were again subdivided into antineurofibrillar, antiperikaryonal-neurofibrillar, and antisynapse-associated groups. On the basis of morphologic, developmental, biochemical, and pathologic criteria, the antibodies in at least two of these groups were found to detect heterogeneous antigens (called "neurotypes") rather than different antigenic determinants in single antigens. On examining the distribution in peripheral organs of staining patterns of 11 antineuronal brain-reactive antibodies, we now confirm that these antibodies are, indeed, largely brain-specific. In general, non-neuronal elements in liver, lung, heart, thymus, intestine, adrenal, and spleen remained unstained. However, most of the antibodies stained peripheral neural elements. Occasional antibodies did stain selected, non-neuronal structures. Four out of five antineurofibrillar antibodies stained nerve fibers in adrenal medulla, intestine and thymus. All of three antiperikaryonal-neurofibrillar antibodies also stained nerve fibers in the adrenal medulla, but not in other organs. Two out of three antisynapse-associated antibodies stained what appear to be nerve contacts on adrenal medullary cells, but not on any other peripheral cells examined. The non-neuronal peripheral staining patterns were restricted to selective nuclear staining exhibited by two out of five antineurofibrillar antibodies and the staining of macrophage and selected cardiac muscle nuclei by two of three antisynapse-associated antibodies. However, one antineurofibrillar antibody also stained the cytoplasm of selected liver cells. Among non-neuronally reacting antibodies, two antibodies stained nuclei of all cells except neurons in brain as well as peripheral organs. An antibody staining the ciliary epithelium of choroid plexus also stained basal bodies of ciliated bronchial epithelium. The overall data suggest that the specificity of brain-reactive antibodies is high and that their cross-reactivity with epitopes in non-nervous tissue is rare. In these cases, the antibodies seem to provide specific reagents for these additional structures as well as for their specific brain antigens.

Animals↗
PubMed1976

An ultrastructural examination of the action of vinblastine on microtubules, neurofilaments and muscle filaments in vitro.

In vitro incubation of autonomic nerves with vinblastine sulphate (1 times 10(-4) M) caused a disappearance of microtubules within 15 min; during the following 15 min paracrystalline arrays appeared within the axons. An increase in the abundance of microfilaments was also observed, but these did not appear to arise from disaggregated microtubules since the increase in microfilament numbers was noted at an incubation time when crystal formation was extensive. Pretreatment of autonomic nerves with colchicine (2.5 times 10(-4) M) caused a reduction of approximately 80% in the numbers of microtubules, but did not prevent the formation of crystals on subsequent exposure to vinblastine. No ultrastru"tural changes were observed in myofilaments on incubation with vinblastine.

Animals↗