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  • 1
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    German Medical Science; Düsseldorf, Köln
    In:  56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3èmes journées françaises de Neurochirurgie (SFNC); 20050507-20050511; Strasbourg; DOC11.05.-16.08 /20050504/
    Publication Date: 2005-05-05
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 2
    ISSN: 1432-0533
    Keywords: Chronic EAE ; Demyelination ; Histopathology ; Guinea pigs ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Besides the essential features of chronic lesions in experimental allergic encephalomyelitis (the chronic perivenous inflammation, the selective demyclination with relative sparing of axons and the reactive gliosis), structural aspects of demyelinating lesions in chronic EAE are variable, depending on the animal species used for the experiments, the time interval between sensitisation and plaque formation, and the localisation of the plaques in the central nervous system (CNS). Species differences mainly included the intensity of the inflammatory response in actively demyelinating lesions, the involvement of local (glial) cells in the removal of myelin debris, the lesional topography in the CNS and the extent of capillary fibrosis in chronic lesions. The extent of demyelination and tissue destruction increased with the time interval between sensitisation and lesion formation, whereas the extent of remyelination in individual lesions decreased in lesions formed at later stages after sensitisation. Brain lesions in comparison to spinal cord plaques were generally characterized by a weaker inflammatory response in active lesions, a prolonged persistence of debris-containing cells, a higher extent of secondary axonal damage, a smaller remyelinating capacity, and only minor perivascular (pericapillary) fibrosis. Since a similar variability in the structure of acute and chronic multiple sclerosis lesions is extensively described in the literature, the above mentioned observations may offer some new information on the pathogenetic mechanisms leading to the structural expression of individual aspects of inflammatory demyelinating lesions.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 77 (1989), S. 276-282 
    ISSN: 1432-0533
    Keywords: Cell kinetics ; Cell cycle ; Brain tumor ; Bromodeoxyuridine ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A newly developed in vitro labeling method with bromodeoxyuridine (BrdU) identifies S phase cells in situ in freshly obtained surgical tissue of human brain tumors which is subsequently fixed and embedded in paraffin for BrdU immunovisualization. For the first time, the BrdU labeling index (LI) is successfully compared here with the LI obtained by immunostaining of frozen sections of the same tumors with monoclonal antibody Ki-67 which identifies all proliferating cells, i.e., the growth fraction. LIs were counted in at least five different areas with high density of labeled cells; at least 1,000 cells were counted. In 13 metastatic tumors, Ki-67 LI was 8.3%–62.6%, and BrdU LI was 5.1%–28.0%. In 18 gliomas, Ki-67 LI was 1.4%–19.3%, and BrdU LI was 0.2%–11.6%. In 7 meningiomas, Ki-67 LI was 0.3%–3.0%, and BrdU LI was 0%–2.0%. Statistical comparison of Ki-67 and BrdU LIs by linear regression analysis revealed a highly significant correlation: BrdU LI=0.99+0.34 Ki-67 LI (r=0.92,P〈0.001). A significant heterogeneity of proliferation patterns may occur within one sample from area to area, as well as between different samples of the same tumor, especially in gliomas; thus, some subjective influence on LIs by arbitrary sampling and selection could occur in quantitative evaluation of in situ cell kinetics of human brain tumors. This study indicates that our in vitro BrdU-labeling method allows the in situ identification of S phase cells in excellently preserved fixed tumor tissue which is well suited for further histological examination. This method compares favorably with Ki-67 labeling of frozen sections and might emerge as a powerful new tool for the routine study of cell proliferation in surgical specimens of human brain tumors.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0533
    Keywords: Chronic relapsing experimental allergic encephalomyelitis ; Blood-brain barrier ; Tracer study ; Cerebrospinal fluid proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Blood-brain barrier (BBB) permeability in chronic relapsing experimental allergic encephalomyelitis was studied morphologically in tracer studies with horseradish peroxidase (HRP) as well as by quantitative determination of HRP, albumin, and IgG in serum and cerebrospinal fluid (CSF), BBB damage was found to be localized in demyelinating plaques and in blood vessels with vasculitis. Actively demyelinating lesions showed massive increase in BBB permeability, whereas in inactive or remyelinated lesions BBB damage was either minimal or absent. Determination of serum proteins in the CSF of animals with severe disease and a high incidence of actively demyelinating lesions showed evidence of BBB damge (reduction of Q-albumin) and an IgG-index in the normal range. In animals with only inactive lesions the Q-albumin was normal, the IgG index, however, was elevated. This finding indicates intrathecal IgG synthesis. A correlation between morphologically visualized tracer leakage in the central nervous system (CNS) with serum protein concentrations in the CSF revealed that elevated CSF albumin is a reliable indicator for BBB damage in lesions, located near the inner or outer surface of the brain and spinal cord. However, singular focal lesions with BBB damage located in the depth of the CNS parenchyma may not be accompanied by CSF protein alterations. The invariable presence of BBB damage in active inflammatory demyelinating lesions and its absence in inactive plaques or in the unaffected nervous tissue may be important in therapy, not only in experimental allergic encephalomyelitis but also in multiple sclerosis (MS).
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  • 5
    ISSN: 1432-0533
    Keywords: Ganglioside-antibodies ; Cholera toxin ; Cytotoxicity ; Demyelination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ganglioside-antisera, the ganglioside GM1-ligands, cholera toxin (CT), and CT subunit B, respectively, were injected into the lumbosacral subarachnoid space of normal rats. The cytotoxic effects of the injected compounds on the peripheral and central nervous system were investigated by light and electron microscopy; the severity of CNS lesions was evaluated by quantitation of macrophages containing debris. In contrast to control sera and GM2-antiserum, antisera against a mixture of the major brain gangliosides GM1, GD1a, GD1b, and GT1b (MaBG) or against GM1 induced demyelination in spinal roots and spinal cord, as well as alterations of astroglia. CT induced the same cytotoxic effects as MaBG- and GM1-antisera, whereas CT subunit B was without effect. The ineffectiveness of GM2-antiserum is obviously due to the very low concentration of the specific binding target, GM2, on cell surfaces; that of CT subunit B to the lack of the cytotoxic operator, subunit A. Our results indicate that a similar pattern of neuropathological lesions may be effected by different cytotoxic mechanisms through attachment of the cytotoxic agent onto the cell surface via a common target molecule, and further substantiate the role of GM1-antibodies in the pathogenesis of demyelination.
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  • 6
    ISSN: 1432-0533
    Keywords: Cell kinetics ; Cell cycle ; Brain tumor ; Cell proliferation ; Nucleolar organizer region proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Proliferation indices and mean number of silver-stained nucleolar organizer region-associated proteins (Ag-NORs) are compared in 65 brain tumors, including 34 gliomas, 8 meningiomas, 17 metastatic tumors, and 6 other tumors. Immunocytochemical investigations include labeling with the monoclonal antibody Ki-67 which identifies the whole growth fraction, and with a monoclonal antibody against bromodeoxyuridine (BrdUrd) which detects cells in the S phase of the cell cycle after in vitro incubation with BrdUrd. When all types of tumors are collectively considered, mean numbers of Ag-NORs did not correlate with Ki-67 and Brd-Urd labeling indices (LIs) and mitotic index. Among tumor subtypes, only meningiomas showed significant correlations between Ag-NOR counts, LIs, and malignancy. Mean number of Ag-NORs did not correlate with proliferation indices and tumor grade in low-grade and high-grade gliomas. However, recurrent high-grade gliomas showed a tendency to higher Ag-NOR counts than primary tumors. This study indicates that counting of Ag-NORs in paraffin sections is of limited value in tumor neuropathology. Correlations found in meningeal tumors should be substantiated in larger series.
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  • 7
    ISSN: 1432-0533
    Keywords: Glioma ; Macrophages ; Microglia ; Fc-receptors ; Complement receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cryostat sections of 12 gliomas and of 3 peritumoral brain tissue samples were investigated for mononuclear cell infiltration by immunohistochemistry, concentrating on cells expressing monocyte/macrophage markers. Only low numbers of T cells were detected in the tumors, whereas in average 20%–30% of all cells present in the samples were recognized by various macrophage markers. These cells carried surface epitopes with known function, like Fc-γ (Fcg) and complement receptors. Microglial cells, in comparison to typical debris laden macrophages, were only recognized by a restricted panel of macrophages markers (anti-Fcg receptors 1, 2, 3, complement receptor CR3, HLA DR, common leucocyte antigen CD45 and the monocyte marker RM3/1). In peritumoral tissue mainly dendritic, microglia-like cells were present, which revealed decreased expression of antigens CD4, RM3/1 and Fcg receptors in comparison to those in gliomas. A significant positive correlation was found between the number of RM3/1 or CR3 (CD11b)-positive cells and the proliferation rate of the tumors as documented by the number of bromodeoxyuridine-positive or Ki-67+ cells.
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  • 8
    ISSN: 1432-0533
    Keywords: Chronic relapsing EAE ; Serum-induced demyelination ; Central demyelination ; Peripheral demyelination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sera from guinea pigs with acute or chronic relapsing experimental allergic encephalomyelitis (EAE) were injected into the lumbosacral subarachnoid space of normal recipient rats. Seventeen of 37 sera induced demyelination in the CNS, and 27 of 37 sera caused demyelinated peripheral nerve fibers in the roots. The highest incidence of demyelinating activity of EAE sera was noted in those from donor animals sampled during the early chronic stage of the disease [40–100 days post sensitization (dps)]. Only few sera from animals sampled during the acute and subacute stage (10–40 dps) were able to induce demyelination. Sera from animals sampled between 100 and 200 dps showed a lower incidence of demyelinating activity as compared to those from the early chronic phase of the disease. There was no clear-cut correlation between the serum-demyelinating activity and the severity of the demyelinating disease in the donor animals. The patterns of demyelination in the central as well as peripheral nervous system of recipient animals were characterized by vesicular disruption of myelin or myelin stripping. Myelin degradation was performed mainly by macrophages. In the CNS some astrocytes also contained debris. Astrocytes increased in size, and mitosis of astrocytes was observed. Oligodendrocytes appeared to be unaffected. No demyelination was found when the sera from animals sensitized with CFA alone or with guinea pig liver tissue were injeted into the subarachnoid space of normal recipient rats. Two possible mechanisms of demyelination are diseussed: Antibody-mediated complement-dependent and antibody-dependent cell-mediated demyelination.
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  • 9
    ISSN: 1432-0533
    Keywords: Cell kinetics ; Cell cycle ; Brain tumor ; Cell proliferation ; Proliferating cell nuclear antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Alcohol- and formalin-fixed, paraffin-embedded samples of 71 brain tumors (35 gliomas, 22 metastatic carcinomas, 8 meningiomas and 6 other tumors) were investigated by immunocytochemistry with three different monoclonal antibodies against proliferating cell nuclear antigen (PCNA)/cyclin (19A2; 19F4; PC10). PC10 was found to work best; it is applicable to both alcohol- and formalin-fixed tumor samples. PCNA labeling indices (LIs) were compared in the same tumors with LIs obtained by Ki-67 immunostaining of frozen sections and by in vitro incubation with bromodeoxyuridine (BrdUrd); in the latter preparations, BrdUrd LIs could be compared with PCNA LIs in the very same areas of serial sections. In gliomas, PCNA LIs were 0.7–80.2% (mean 31.7%), in metastases 0–76.0% (mean 47.8%), and in meningiomas 0–53.0% (mean 19.3%). In general, PCNA LIs were highly significantly correlated with Ki-67 LIs (P=0.0002) and BrdUrd LIs (P=0.0001). However, when tumor subgroups are considered, only gliomas show a significant correlation with Ki-67 and BrdUrd LIs. Despite this statistical correlation, PCNA expression was out of proportion to proliferation indices as determined by both other methods in almost one third of all brain tumors. Immunocytochemistry for PCNA produces a broad spectrum of staining intensity of labeled nuclei, whose number is dependent upon the sensitivity of the immunocytochemical technique used. Thus, inter-oberserver and inter-laboratory variabilities in PCNA LI determination may occur. Overlapping of PCNA LIs between tumor subgroups of varying malignancy further limits the informational value for the individual case. In some classic meningiomas, high PCNA scores do not reflect the proliferative activity of the tumor, as Ki-67 and BrdUrd LIs are very low in these cases. We conclude that PCNA immunolabeling is of limited value in the individual tumor, mainly due to overexpression in many tumors, and at present cannot be recommended to replace Ki-67 and/or BrdUrd labeling methods for routine determination of proliferative activity in human tumor specimens.
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  • 10
    ISSN: 0942-0940
    Keywords: Keywords: Stereotactic radiosurgery; meningioma; skull base; brain tumour.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary  Background. The standart surgical treatment of meningiomas is total resection of the tumour. The complete removal of skull base meningiomas can be difficult because of the proximity of cranial nerves. Stereotactic radiosurgery (SRS) is an effective therapy, either for adjuvant treatment in case of subtotal or partial tumour resection, or as solitary treatment in asymptomatic meningiomas.  Method. Between September 1992 and October 1995, SRS using the Leksell Gamma Knife was performed on 46 patients (f:m=35:15), ranging in age from 35 to 81 years, with skull base meningiomas at the Neurosurgical Department of the University of Vienna. According to the indication of gamma knife radiosurgery (GKRS) the patients (n=46) were devided into two subgroups. Group I (combined procedure: subtotal resection followed by GKRS as a planned procedure or because of a recurrent meningioma), group II (GKRS as the primary treatment). Histological examination of tumour tissue was available for 31 patients (67%) after surgery covering 25 benign (81%) and 6 malignant (19%) meningioma subtypes.  Findings. The overall tumour control rate after a mean follow-up period of 48 months (ranging from 36 to 76 months) was 96% (97.5% in benign and 83% in malignant meningiomas). Group I displayed a 96.7% tumour control rate, followed by group II with 93.3% respectively. Neurological follow-up showed an improvement in 33%, stable clinical course in 58% and a persistant deterioration of clinical symtoms in 9%. Remarkable neurological improvement after GKRS was observed in group II (47%), whereas in group I (26%) the amelioration of symptoms was less pronounced.  Interpretation. GKRS in meningiomas is a safe and effective treatment. A good tumour control and low morbidity rate was achieved in both groups (I, II) of our series, either as a primary or adjunctive therapeutic approach. The planned combination of microsurgery and GKRS extends the therapeutic spectrum in the treatment of meningiomas. Reduction of tumour volume, increasing the distance to the optical pathways and the knowledge of the actual growing tendency by histological evaluation of the tumour minimises the risk of morbidity and local regrowth. Small and sharply demarcated tumours are in general ideal candidates for single high dose-GKRS, even after failed surgery and radiation therapy, and in special cases also in larger tumour sizes with an adapted/reduced margine dose.
    Type of Medium: Electronic Resource
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