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Biomedical subjects

A Migheli

Publications and source records attributed to A Migheli.

70 records · Page 4Linked to original sources

Light and electron microscope localization of the microtubule-associated tau protein in rat brain.

We have studied the distribution of microtubule-associated tau proteins in rat brain using monoclonal and affinity-purified polyclonal antibodies. Tau staining is prominent in axons in white matter areas of brain, as reported by Binder et al. (1985). In addition, we also find tau protein in neuron cell bodies, especially in the brain stem and basal ganglia and in the cell bodies of interfascicular oligodendroglia. Using electron microscopy, tau antibodies and colloidal gold-labeled second antibodies, gold particles are found associated with microtubules in axons and in the cytoplasm of cell bodies, while the nuclei, mitochondria, and myelin remain unlabeled. In double-staining experiments, tau staining co-localizes with that of tubulin. Our studies indicate that tau proteins are more widely distributed in brain than previously reported and cannot be used as an exclusive marker for axons.

Animals↗

In vitro formation of amyloid fibrils from two synthetic peptides of different lengths homologous to Alzheimer's disease beta-protein.

Two synthetic peptides corresponding to the reported 28-residue sequence of Alzheimer's Disease beta-protein (SP28) and to residues 12-28 (SP17) were used to form fibrils in vitro. Synthetic fibrils bound Congo Red and closely resembled amyloid fibrils isolated from leptomeninges and senile plaques of Alzheimer's brain by electron microscopy. A polyclonal antiserum to SP28 specifically decorated both synthetic and native amyloid by colloidal gold immunoelectron microscopy. Amyloid fibrils isolated from tissue were insoluble on SDS-Polyacrylamide gels, and tended to aggregate while synthetic amyloid fibrils were completely solubilized, releasing only monomers of SP28 and SP17. Anti-SP28 immunostained cerebrovascular and plaque core amyloid, but not neurofibrillary tangles, in tissue section. Western blot analysis showed that anti-SP28 reacted with a 4 kDa band released from amyloid core-enriched preparations and leptomeninges. By contrast, a 16 kDa band corresponding to the tetramer of beta-protein was not recognized. These data suggest that as little as a 17 residue sequence of beta-protein may be required to form fibrils and that the complete sequence of the 4 kDa beta-protein may be important in determining insolubility and the formation of intermediate size polymers.

Alzheimer Disease↗

Glial fibrillary acidic protein and vimentin in the experimental glial reaction of the rat brain.

Glial reaction has been studied in the rat by the immunohistochemical demonstration of glial fibrillary acidic protein (GFAP) and vimentin (VIM) in two experimental conditions. The first was represented by a necrotic cerebral lesion obtained by laser irradiation and the second by the development of experimental tumors induced by transplacental ethylnitrosourea. Reactive astrocytes develop not only in the proximity of the lesion but also distant from it. The intensity of the glial response seems to depend upon the normal distribution of astrocytes and the perilesional edema. GFAP decorates all the reactive astrocytes, whereas VIM is positive only in those at the edges of the lesion. The significance of the different responses in the two models and between the two intermediate filaments is discussed.

Animals↗

Immunohistochemical demonstration of vimentin in human cerebral tumors.

The distribution of vimentin (VIM) has been histochemically investigated in 53 cerebral tumors and compared in gliomas to that of glial fibrillary acidic protein (GFAP). In gliomas VIM is less positive than GFAP, but shows the same distribution. It cannot be considered as indicating immaturity of glial tumor cells. VIM is also positive in glial processes of cerebellar pilocytic astrocytomas, in Schwann cells of neurinomas and in endothelial cells of all oncotypes. In medulloblastomas, VIM decorates reactive glia cells. A diffuse positive reaction has been observed in meningiomas. In hemangioblastomas, besides intervascular and endothelial cells, groups of polygonal cells are intensely positive for both VIM and GFAP. The interpretation of VIM in cerebral tumors is largely based on the distribution patterns of this intermediate filament in the developing CNS of rodents.

Astrocytoma↗

Clinical-anatomic study of a family with bulbo-spinal muscular atrophy in adults.

Four cases are presented, with bulbo-spinal muscular atrophy characterised by adult onset and rapid evolution. They belong to a family in which the type of inheritance is probably dominant. Two cases were studied histologically. The most striking feature was the disappearance of neurons in the lower motor nuclei of medulla and of the spinal anterior horns. An electron microscopic study was carried out in one case. Accumulation of neurofilaments was a general characteristic, in addition to the picture of different sized spheroids. The clinical-pathological relationship is discussed.

Adult↗

Immunohistochemistry in neuro-oncology.

The technical modalities of the immunohistochemical demonstration of antigens of neuroectodermal differentiation and of mesenchymal nature in neural tissue are discussed. On the main antigens (S-100 protein, GFAP, Vimentin, Neuronal specific Enolase, neurofilaments, myelin basic protein, carboanhydrase C, FVIII/RAg, laminin, fibronectin) the most important findings are described and critically considered. They are interpreted in the light of the present knowledge on the problems of differentiation of the oncotypes and on particular aspects of bio-pathology of brain tumors.

Astrocytes↗

The distribution of laminin in human brain tumors: an immunohistochemical study.

The immunohistochemical distribution of laminin in 70 cases of primary and secondary brain tumors has been studied. The sections were fixed in Carnoy, embedded in paraffin, and treated with collagenase before applying the specific immune serum. In normal neural tissue and in gliomas, the distribution of laminin overlaps with that of basement membrane, as is known from observations on ultrastructure in the literature. The overlapping was observed also in neurinomas, papillomas of the choroid plexus, ependymomas, and meningiomas. Problems arise in the interpretation of the results in the other oncotypes. In hemangiopericytomas and hemangioblastomas, laminin demonstrates a basement membrane around the vessels only; it is absent around stromal cells. In desmoplastic medulloblastomas, laminin forms a network among the tumor cells. In primary lymphomas, concentric rings of laminin are evidenced around some vessels. In discussing the results, the ultrastructural distribution of basement membranes is taken into account.

Basement Membrane↗

Collagenase in the immunohistochemical demonstration of laminin, fibronectin and factor VIII/RAg in nervous tissue after fixation.

The effects of collagenase on the immunohistochemical demonstrability of laminin, fibronectin and Factor VIII/RAg in human nervous tissue have been studied. The influence of this, and other proteolytic enzymes such as pepsin and trypsin, has been investigated in relation to different fixatives. Collagenase gave better results with Carnoy fixed material than after formalin fixation; unlike trypsin and pepsin, it did not produce tissue digestion.

Antigens↗

GFAP, F VIII/RAg, laminin, and fibronectin in gliosarcomas: an immunohistochemical study.

GFAP, Factor VIII/RAg, laminin, and fibronectin were immunohistochemically investigated in 15 glioblastomas and 15 gliosarcomas . GFAP was found variably positive in the glial areas. F VIII/RAg characterizes the endothelial cells and in gliosarcomas suggests the origin of the sarcomatous component from the endothelial proliferations. Laminin separates the two components and characterizes the inner and the outer basement membranes in the vessels. It is multiplied and thickened in endothelial proliferations, while it is often fragmented in the larger vessel wall proliferations. Our observations confirm that gliosarcoma represents the last stage of a process which starts with the endothelial hyperplasia of glioblastoma.

Antigens↗

Glial fibrillary acidic protein (GFAP) in human cerebral tumors. An immunohistochemical study.

Glial fibrillary acidic protein (GFAP) was studied in 160 cerebral tumors, mostly of neuro-epithelial nature. It was positive in astroglial tumors with an intensity proportional to the degree of cell differentiation. It was sometimes positive also in non-astroglial tumors, such as oligodendrogliomas and ependymomas, and this finding is discussed in relation to genesis and diagnostic value. In medulloblastomas, there were also positive cells, which could be reactive glia cells included in the tumors or subependymal cells. The demonstration of GFAP is very useful in gliosarcomas for identifying the glial component. It was sometimes positive in hemangioblastomas, and it is discussed in view of the nature of the stromal cells of this tumor.

Brain Neoplasms↗

Biochemical and histochemical evaluation of glycosaminoglycans in brain tumors induced in rats by nitrosourea derivatives.

The occurrence, distribution and concentration of GAGs in ENU and MNU experimental brain tumors induced in the rat are reported. GAGs have been histochemically studied by Alcian Blue methods; they have been quantified and qualitatively evaluated by electrophoresis of brain extracts. The pattern of GAGs in normal rats is consistent with the data of the literature. No GAG accumulation precedes the tumor development. Early neoplastic proliferations, oligodendroglial and mixed glial microtumors are strongly alcian-positive; the alcianophilia spares clusters of cells developing a cytoplasm. In large tumors, GAGs are histochemically demonstrable in the honey-comb areas of oligodendrogliomas and in peripheral infiltration areas of polymorphic gliomas. The role of the normal nervous tissue and oligodendroglial cells in the accumulation of the GAGs is discussed. The accumulated GAGs seem to rise from the nervous tissue included in the tumors, rather than from the metabolism of tumor cells.

Age Factors↗

Contributions of immunohistochemistry to the problem of differentiation in medulloblastoma.

The problem of differentiation of medulloblastoma is considered. In this regard 43 medulloblastomas, showing cells with glial or neuronal features by routine histologic methods, were studied. The investigation was carried out by means of the immunohistochemical demonstration of the glial fibrillary acidic protein (GFAP) and the neuron-specific enolase (NSE). In most cases, GFAP-positive cells are preexisting astrocytes; in two cases they correspond to the transitional cells of the subependymal layer. NSE was demonstrated in areas filled with cells with neuroblastic features. The relationship between medulloblastoma with neuron-differentiation and cerebellar neuroblastoma is discussed.

Astrocytes↗

Glycosaminoglycans in human cerebral tumors. Part II. Histochemical findings and correlations.

The occurrence and the distribution of GAGs have been studied histochemically in 224 human cerebral tumors by means of Alcian blue techniques. In the normal peritumoral gray matter the alcianophilia is stronger than in the white matter and demonstrated the presence of HA and CS. In the glioma group the alcianophilia, due to HA and CS, is mainly related to the presence of infiltrated cortex. In the other tumors, GAGs are histochemically disclosed in relation to collagen, reticulin, mesodermic areas, etc. The vessels of every tumor show a positive staining for HA, CS and HS. The histochemical findings are consistent with the biochemical ones as reported in Part I, even though the significance of GAGs in cerebral tumors remains unknown.

Astrocytoma↗

Glial fibrillary acidic protein (GFAP) in rat brain tumors transplacentally induced by ethylnitrosourea (ENU).

The immunohistochemical distribution of glial fibrillary acidic protein (GFAP) in neoplastic lesions induced in the rat by ENU is reported. GFAP was present in hypertrophic reactive astrocytes, which were numerous in early neoplastic proliferations, in microtumors of the white matter, and in those collected at the periphery of large tumors. They were absent in cortical oligodendroglial foci and microtumors. No GFAP-positive cells were observed in hyperplasias of the white matter: astrocyte-like cells of large tumors were GFAP-negative. The significance of reactive astrocytes and the problem of the astrocytic component in transplacental ENU tumors are discussed.

Animals↗

Ultrastructural immunocytochemistry in glial tumors.

We have studied the ultrastructural distribution of GFAP, vimentin, FVIII/RAg and collagen IV in biopsies of human gliomas with various degree of anaplasia. Pre-embedding (vibratome and cryoultrathin sections) and post-embedding (LR White sections) techniques were tested. The immune reaction was demonstrated by peroxidase-DAB and gold labeling. In astrocytes, GFAP and VIM were localized in the same filament bundles; GFAP was always more expressed than vimentin, regardless of the malignancy grade. FVIII was localized in endoplasmic reticulum and in Weibel-Palade bodies. The influence of technical procedures on the optimal demonstration of each antigen is stressed.

Collagen↗

Spongiform encephalopathy in addicts inhaling pre-heated heroin.

Three subjects, inhaling pre-heated heroin, developed a severe neurological illness. The neuropathological examination at autopsy on two of them demonstrated that it was due to a spongiform encephalopathy. By light and electron microscopy a severe edema with spongiosa and myelin damage were evident. U-fibers, brainstem, spinal cord and peripheral nerves were spared. The origin of the encephalopathy was not identified. The encephalopathy of our cases is similar to that described by Wolters et al. in 1982 in Holland.

Adult↗