Search PubMed⌕ Search

Biomedical subjects

G Perry

Publications and source records attributed to G Perry.

At least 217 records · Page 12Linked to original sources
PubMed1991

Tropomyosin distinguishes Lewy bodies of Parkinson disease from other neurofibrillary pathology.

Research into the cellular changes in the degenerative diseases of the central nervous system has focused on the alterations in the constituent proteins of the neuronal cytoskeleton. Although both microtubule and neurofilament proteins have been implicated in the formation of neurofibrillary pathology in Alzheimer, Pick, diffuse Lewy body and Parkinson diseases and progressive supranuclear palsy (PSP), until recently there has been little consideration of whether other cytoskeletal systems are involved. With the findings that epitopes of the microfilament associated protein tropomyosin are present in the neurofibrillary pathology of Alzheimer disease, we decided to investigate the presence of this protein in these related diseases. To address whether the inclusion bodies of other degenerative diseases share this property, sections of brain were immunostained with antibodies to smooth and skeletal muscle tropomyosin. Although neurofibrillary tangles in PSP, Pick bodies and some diffuse Lewy bodies stained, Lewy bodies of idiopathic Parkinson disease did not. This property further distinguishes the Lewy body of Parkinson disease from other neurofibrillary pathologies.

Aged↗
PubMed1991

Widespread serum amyloid P immunoreactivity in cortical amyloid deposits and the neurofibrillary pathology of Alzheimer's disease and other degenerative disorders.

Amyloid P (AP) component is present in all types of systemic amyloid deposits. Recently, it has been shown to be also present in cerebral amyloid lesions of Alzheimer's disease (AD). In this study, we used immunocytochemical methods to extend these findings at the electron microscope level and characterize the spectrum of AP immunoreactivity in neurofibrillary pathology (NFP) of AD and other neurodegenerative disorders including Down's syndrome (DS), Creutzfeldt-Jakob, Parkinson's, Pick's and diffuse Lewy body diseases and progressive supranuclear palsy. In AD and DS, AP immunoreaction product was evident in all the classical amyloid lesions and NFP in a large sample of all cortical areas examined. The distribution and relative intensity of immunostaining was similar to that of thioflavin S staining in serial sections. In many cases, however, plaques and vessels stained by anti-AP serum were not apparent with thioflavin S. Serial sections immunostained with antiserum to amyloid A, C-reactive protein or to other proteins involved in systemic amyloidoses and the acute phase response showed no evidence of staining in any of the cerebral lesions. Electron microscopy confirmed that AP immunoreactivity was associated with the abnormal filaments characteristic of NFP as well as amyloid fibrils found in plaques and vessels showing congophilic amyloid angiopathy. Plaques of Creutzfeldt-Jakob disease, Pick bodies of Pick's disease, tangles and Lewy bodies in Parkinson's disease and a subpopulation of Lewy bodies in the diffuse Lewy body disease coexistent with AD were also stained. With the exception of vessels in two of the five cases, AP was not detected in age-matched controls. Our observations indicate AP to be a consistent feature of cerebral NFP and amyloid deposits.

Adult↗
PubMed1991

Basic fibroblast growth factor binding is a marker for extracellular neurofibrillary tangles in Alzheimer disease.

Neurofibrillary tangles (NFT) are abnormal filamentous inclusions that develop in neurons in Alzheimer disease and other disorders. When neurons die, the neurofibrillary tangles that persist in the extracellular space show ultrastructural and antigenic changes. Both intra- and extracellular NFT have recently been shown to contain heparan sulfate proteoglycans (HSPGs). HSPGs are also present in other amyloid deposits in the brain and in systemic amyloidoses. Basic fibroblast growth factor (bFGF) is a heparin binding growth factor which is involved in angiogenesis and also has neurite promoting activity. We now report that bFGF binds avidly to extracellular NFT. Alz-50, a monoclonal antibody (MAb) to an abnormal form of tau and bFGF binding label mutually exclusive subpopulations of neurofibrillary tangles. bFGF binding is abolished by heparinase or heparitinase treatment and therefore is most likely based on the presence of HSPG. Binding of bFGF is a specific and sensitive morphological method to distinguish intra- from extracellular NFT. As intracellular NFT, which also contain HSPGs, are not labeled by bFGF binding, this finding also suggests that HSPGs are modified when the NFT become extracellular.

Aged↗
PubMed1991

Abnormal tau-reactive filaments in olfactory mucosa in biopsy specimens of patients with probable Alzheimer's disease.

We immunocytochemically analyzed pieces of olfactory mucosa removed by biopsy in 8 patients with probable Alzheimer's disease (AD) and 6 age-matched controls, with tau and ubiquitin antisera. There were tau-reactive and, partially, ubiquitin-reactive dystrophic neurites in the lamina propria of olfactory mucosa in all AD cases. The tau-reactive neurites contained abnormal straight filaments, 15 to 18 nm in diameter, morphologically identical to those found in AD cerebral brain tissue obtained at autopsy. Tau and ubiquitin immunoreactivity were absent in controls. If these neuritic alterations are confirmed in a larger number of cases, analysis of olfactory mucosa may increase the current reliability of clinical diagnosis of AD.

Alzheimer Disease↗
PubMed1991

Cytokeratin expression in human spinal meninges and ependymal cells.

The expression of intermediate filament protein in human spinal cord arachnoid cells and ependyma was studied by immunohistochemistry and immunoblotting. Monoclonal antibodies specific for individual cytokeratin polypeptides indicated a developmental change in the presence of cytokeratin 8 and 18 in spinal leptomeninx and tanycytes of the spinal cord ependyma. While in fetal material cytokeratin 8 and 18 were abundant in arachnoid cells, in adults immunoreactivity was restricted to a few cells. Immunoblots prepared from adult as well as fetal arachnoid membranes showed significant amounts of cytokeratin 8. These findings indicate that although cytokeratin is represented in both fetal and adult arachnoid cells there is development regulation of its specific localization.

Adult↗
PubMed1991

Neuropil threads of Alzheimer's disease show a marked alteration of the normal cytoskeleton.

Abnormal neurites, neuropil threads, are a widespread and characteristic lesion of Alzheimer's disease likely to play a major role in the cognitive impairment of this disease. Contrary to normal neurites, neuropil threads contain straight and paired helical filaments that contain the microtubule-associated protein tau and ubiquitin. It is not known whether these abnormal filaments are added to or replace the normal cytoskeleton. In this study, we examined the fine structure of neuropil threads and carried out a morphometric analysis of the neurofilaments and abnormal filaments contained in the neuropil threads by using an antiserum to tau and colloidal gold immuno-electron microscopy. Almost 70% of the neuropil threads contained straight or paired helical filaments with no neurofilaments. The total number of filaments in each neuropil thread remained essentially unchanged either when straight or paired helical filaments were present alone or when they coexisted either together or with neurofilaments. When the three types of filaments were expressed as a proportion of the total, a linear inverse correlation was found between neurofilaments and straight filaments as well as between straight and paired helical filaments. Approximately 10% of the neuropil threads were found to be myelinated axons. It is concluded that straight filaments are likely to replace neurofilaments, that they in turn might be replaced by paired helical filaments, and that this process occurs in axons as well as dendrites.

Aged↗
PubMed1991

Association of heparan sulfate proteoglycan with the neurofibrillary tangles of Alzheimer's disease.

The major intracytoplasmic lesion of Alzheimer's disease is the neurofibrillary tangle (NFT), which is primarily composed of paired helical filaments (PHFs). The mechanism responsible for the formation of PHFs, as well as their insolubility and apparent heterogeneity, is unknown. We found that basic fibroblast growth factor (bFGF) binds to heparinase-sensitive sites in NFTs. bFGF binding is due to a heparan sulfate proteoglycan (HSPG) immunocytochemically identified in NFTs. In the presence of polycations (e.g., Ca2+), HSPG will bind to free carboxyl groups in NFT proteins. HSPG binding may play a role in transforming normal soluble proteins into insoluble PHFs.

Aged↗
PubMed1990

Antigenic profile of plaques and neurofibrillary tangles in the amygdala in Down's syndrome: a comparison with Alzheimer's disease.

Most patients with Down's syndrome (DS) undergo a premature cognitive decline with aging, and eventually develop the neuropathologic changes of Alzheimer's disease (AD), including amyloid-containing neuritic plaques, and the formation of neurofibrillary tangles. The amygdala is a focus of marked neuropathologic change in older patients with DS and in AD. We examined the amygdala with immunocytochemical and histochemical methods in 6 cases with DS, ages 19, 20, 27, 29, 56 and 64 years and compared them to 4 cases with AD, ages 54, 76, 77 and 80 years. An antiserum to the A4 amyloid peptide demonstrated amyloid deposition in plaques in all 10 cases. Plaques were also revealed in all cases by the Alcian blue stain for glycosaminoglycans and by the Bielschowsky and Bodian silver stains. An antiserum to alpha-1-antichymotrypsin (ACT) showed plaques in the AD cases and in the 19, 56 and 64 year old DS cases. Neurofibrillary tangles were observed with silver stains only in the older DS and in the AD cases, and not in the 19, 20, 27 and 29 year old DS cases. Likewise, antisera to paired helical filament, to microtubule associated proteins tau and microtubule associated protein-2 (MAP-2), and to ubiquitin, all of which are components of neurofibrillary tangles, reacted with tangles and abnormal neurites only in the older DS and the AD cases. An antiserum to neurofilament epitopes labeled NFTs in the older DS cases and the AD cases, but not in the younger DS cases, except for two intraneuronal NFTs in the 27 year old case.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Role of cytokeratin intermediate filaments in transhepatic transport and canalicular secretion.

The role of cytokeratin filaments in the function of hepatocytes was investigated using a nickel-treated hepatocyte in vitro model. Cytokeratin intermediate filaments were selectively dissociated from the cell cortex by nickel treatment. Cytokeratins and ubiquitin were observed using immunofluorescence and immunoelectron microscopy. Hepatocytic function was assessed by visualizing uptake, transhepatic transport and secretion of fluorescein diacetate and horseradish peroxidase into the bile canaliculi. In control primary cultures, most of the bile canaliculi were surrounded by an inner layer of actin filaments and an outer pericanalicular sheath of cytokeratin filaments and microtubules. The cytoplasmic distribution of ubiquitin was diffuse and particulate. After treatment with NiCl2 (150 micrograms/ml) for 24 hr, the cytokeratin filaments and desmoplakin became focally detached from the cell cortex and retracted to form an aggregate around the nucleus. These aggregates were associated with intense ubiquitin immunoreactivity. Only a few attachments of the cytokeratin filaments to the cell cortex remained. F-actin remained attached to the cell cortex in the areas where the cytokeratin filaments had become detached. The pericanalicular sheath of cytokeratin filaments and the bile canaliculi disappeared and actin was dispersed over the entire cell periphery. Fluorescein diacetate secretion and horseradish peroxidase uptake were almost completely absent in the hepatocytes treated with nickel. The effects of nickel persisted 24 hr after its removal from the medium. It is concluded that cytokeratin intermediate filaments play a critical role in the formation of the bile canaliculus, secretion of fluorescein diacetate and uptake of horseradish peroxidase. Further, our study indicates that cytokeratin ubiquitination occurs during collapse and aggregation of the cytokeratin filaments. The formation of cytokeratin-ubiquitin conjugates during aggregation suggests a role of ubiquitin in the control of cytokeratin organization in hepatocytes in the response to cell stress.

Animals↗
PubMed1990

Immunohistochemical recognition of ethylnitrosourea induced rat brain microtumors by anti-Leu 7 monoclonal antibody.

This immunocytochemical study was undertaken to clarify the histogenesis of ethylnitrosourea-induced rat brain tumors. The tumors induced in offspring of Sprague-Dawley rats injected with ethylnitrosourea on day 18 of gestation were used in these experiments. Controls consisted of pregnant Sprague-Dawley rats similarly injected with saline alone. Both microtumors (less than 1 mm) and macrotumors were examined immunocytochemically. The cells present in both macro- and microtumors were reactive with anti-Leu 7, an antibody which recognizes oligodendrocytes. Intermixed with, but distinct from the tumor cells were glial fibrillary acidic protein positive cells morphologically identical to astrocytes found in other areas distant to tumors in the treated animals, and in controls. These data suggest that both early and late tumors are oligodendrogliomas, not astrocytomas or mixed gliomas, and that the cell of origin of the tumor is the oligodendrocyte rather than an uncommitted stem cell as previously suggested.

Animals↗
PubMed1990

Glucose transporters are abundant in cells with "occluding" junctions at the blood-eye barriers.

We studied the distribution of the "erythroid/brain" glucose transporter protein in the human and rat eye by immunocytochemistry with monoclonal and polyclonal antibodies to the C terminus of the human erythrocyte glucose transporter. We found intense immunocytochemical staining in the endothelium of microvessels of the retina, optic nerve, and iris but not in microvessels of the choroid, ciliary body, sclera, and other retro-orbital tissues. In addition, we found marked immunocytochemical staining of retinal pigment epithelium, ciliary body epithelium, and posterior epithelium of the iris. The common feature of all those endothelial and epithelial cells that stained intensely for the glucose transporter is the presence of "occluding" intercellular junctions, which constitute the anatomical bases of the blood-eye barriers. We propose that a high density of the glucose transporter is a biochemical concomitant of epithelial and endothelial cells with barrier characteristics, at least in tissues that have a high metabolic requirement for glucose.

Animals↗
PubMed1990

Tropomyosin isoform expression in normal and neoplastic astrocytes.

Changes of tropomyosin isoforms have previously been found accompanying morphologic alterations such as those associated with neoplastic transformations in mammalian cells. To determine whether an isoform change is associated with the malignancy of brain tumors, we employed both polyclonal antibodies specific to high and low molecular weight tropomyosin isoforms. We found, by using immunocytochemistry and immunoblotting, that an alteration of tropomyosin isoforms is associated with human astrocytomas. Differential staining patterns were seen for normal, reactive, and neoplastic astrocytes. Characterization of the antibodies revealed an increase in the higher molecular weight tropomyosin in more anaplastic astrocytomas than in those that were well differentiated. We also observed that the different isoforms have specific subcellular localizations. These findings suggest that neoplastic transformation is associated with alteration of tropomyosin isoforms in astrocytomas. We speculate that this change may be related to morphologic transformation in which microfilament functions, such as cell shape, interaction, and recognition are altered.

Adolescent↗
PubMed1990

Age-dependent pattern of intermediate filament protein expression in the human pineal gland.

Intermediate filament distribution was studied in children and adult human pineal glands by using immunocytochemistry and immunoblotting. The demonstration of cytokeratin positive cell clusters in the infant pineal gland may be related to ependymal cells arising from the subcommissural organ. The SCO ependymal cells and the ependymal cells in the pineal parenchyma express the neuro-ectoderm specific individual cytokeratins no. 8 and 18. Cytokeratin positive ependymocytes additionally exhibited vimentin and were serotonin negative as revealed by double immunofluorescence labelling. By contrast, in adult pineal glands cytokeratin positive cells were not clustered. An interesting but unexplained increase of neurofilament 68 KD positive nerve fibres was detectable.

Adult↗
PubMed1990

Neuronal and microglial involvement in beta-amyloid protein deposition in Alzheimer's disease.

This study was undertaken to localize amyloid precursor protein (APP) and to determine how APP might be released and proteolyzed to yield the beta-amyloid protein deposits found in senile plaques in the brains of Alzheimer's disease patients. We found that antibodies to recombinantly expressed APP labeled many normal neurons and neurites. In addition, dystrophic neurites in different types of senile plaques and degenerating neurons in the temporal cortex and hippocampus of Alzheimer's disease patients were immunostained. We also detected small clusters of dystrophic APP immunoreactive neurites that were not associated with beta-amyloid protein deposits. Microglia was involved in different types of senile plaques and often were associated closely with APP immunoreactive neurites and neurons. The greatest concurrence of APP immunoreactivity and reactive microglia was seen in the subiculum and area CA1, regions with a high density of congophilic plaques and subject to intense Alzheimer's pathology. Our findings suggest that neuronally derived APP is the source for senile plaque beta-amyloid protein, while microglia may act as processing cells.

Aged↗
PubMed1990

The relationship of amyloid plaques to cerebral capillaries in Alzheimer's disease.

The authors examined the hypothesis that senile plaques of Alzheimer's disease (AD) are formed by abnormal leakage of amyloidogenic precursors from brain capillaries by quantitative analysis of the spatial relationship between capillaries and amyloid plaques. Vibratome sections (40 mu) of the hippocampus, including the entorhinal cortex, obtained at autopsy from AD subjects, were immunostained with a monoclonal antibody to beta-protein and counterstained with rabbit serum to either the glucose transporter protein, a cerebral endothelial marker, or collagen type IV, a basal lamina marker. The authors found that while 60% to 77% of amyloid plaques were associated with capillaries, only 8% to 13% were penetrated by a capillary, the remainder being adjacent. To test whether 1) the area occupied by amyloid plaques or 2) the border zone (10-mu rim) surrounding amyloid plaques has a statistically higher density of capillaries than 3) the remaining gray matter, similarly double-stained 6-mu sections from five AD subjects were photographed and the capillary densities in the three areas calculated. Capillary density was significantly lower in 1) than in 3) and higher in 2) than in 3), while the combined area of 1) and 2) showed the same capillary density as 3). Similar results were obtained by using either the glucose transporter or the collagen type IV antibodies. Because capillary density is low within, and high in regions that immediately surround amyloid plaques, our findings suggest that amyloid plaques exclude capillaries or lead to their degeneration, or both. The latter possibility was investigated by triple-staining tissue sections with antibodies to beta-protein, glucose transporter, and collagen type IV. The proportion of glucose transporter-negative capillaries was not significantly different in areas inside or outside of the plaques. Thus, the authors found no evidence of basal lamina remnants consistent with capillary degeneration preferential to amyloid plaques. Although a small number of capillaries showed amyloid deposition just beneath the basement membrane, the authors conclude that capillaries play only a limited direct role, if any, in amyloid plaque formation, and that the apparent association of amyloid plaques and capillaries is no more than a chance contact.

Alzheimer Disease↗
PubMed1990

Immunocytochemical localization of the erythroid glucose transporter: abundance in tissues with barrier functions.

We investigated the cellular localization and tissue distribution of the glucose transporter protein in the nervous system of the monkey and rat, and in other tissues of the rat, by immunocytochemical methods with monoclonal and polyclonal antibodies to the glucose transporter of human erythrocytes. We found intense immunostaining, indicating a high density of the glucose transporter, in all intraparenchymal blood vessels of the brain and spinal cord, in pial vessels, and in endoneurial capillaries of peripheral nerves, nerve roots, and dorsal root ganglia. Larger blood vessels at the base of the brain and in major fissures did not stain. The only intraparenchymal brain microvessels that did not immunostain were in circumventricular organs. There was no specific immunostaining of neurons or glia, except for tanycytes in the floor of the third ventricle, which immunostained intensely. Vessels of the choroid plexus did not stain, but the choroid epithelium, especially its basal membranes, stained. The only non-neural organ where immunostaining was evident in its microvessels was the testis. In addition to the endothelium of neural and testicular tissues, there was immunostaining in certain epithelial tissues, such as the perineurium of peripheral nerves and nerve roots, the epithelium of the ascending loop of Henle in the kidney, and the epidermis of the skin. Based on these findings, we hypothesize that a high density of the erythroid-type glucose transporter is inherent to many endothelial and epithelial cells that are joined by occluding junctions. However, other epithelial tissues with known occluding intercellular junctions that lack the erythroid-type of glucose transporter may have other types of glucose transporter proteins.

Animals↗
PubMed1990

Immunochemical demonstration of tropomyosin in the neurofibrillary pathology of Alzheimer's disease.

The focus of research on the neurofibrillary pathology (NFP) of Alzheimer disease has been not only to determine the component forming the paired helical filaments but also to determine whether they result from abnormal processes affecting a single protein. Therefore, although these studies have lead to controversy concerning the respective contribution of components of microtubules and neurofilaments, there has been essentially no consideration of whether other cytoskeletal systems might also be involved and of what are the common features for the incorporated components. Particularly relevant to this issue is our finding that several antisera raised to either skeletal or smooth muscle tropomyosin, a microfilament component, intensely recognize NFP. These antibodies continue to recognize NFP after affinity purification to tropomyosin or paired helical filament fractions. We show that the antibodies do not recognize NFP due to cross-reactivity with the previously identified NFP components related to neurofilaments and microtubules, tau, and MAP2, or neurofilament proteins because the antisera did not recognize these proteins on immunoblots or were not adsorbable by the proteins. Ultrastructural analysis of the immunoreaction showed that tropomyosin-related epitopes were clustered rather than uniformly distributed along paired helical and straight filaments. Although the distribution suggests that tropomyosin is an NFP-associated protein, its retention by paired helical and straight filaments after detergent extraction indicates that it is an integral component strongly and specifically associated with the filaments characteristic of NFP. These findings indicate that NFP involves the three primary neuronal cytoskeletal filament systems, microtubules, neurofilaments, as well as microfilaments, and therefore that NFP probably results from the reorganization of these normal filaments that interact to comprise the cytomatrix and may continue this interaction under the pathologic condition of Alzheimer's disease to generate novel, abnormal polymers.

Actin Cytoskeleton↗