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  • Articles: DFG German National Licenses  (42)
  • Electronic Resource  (42)
  • 11
    ISSN: 1432-0533
    Keywords: Medulloblastoma ; S-Antigen ; Rod-opsin ; Prognosis ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Biopsy specimens of 66 medulloblastomas were investigated by means of S-antigen and rod-opsin immunocytochemistry. The patients were operated between 1969 and 1988 and the medical records were retrospectively evaluated to correlate the immunocytochemical features of the tumors to the course of the disease. S-antigen- and rod-opsin-immunoreactive tumor cells were found in 19 out of 66 cases. Since in the normal non-neoplastic state immunoreactive S-antigen and rod-opsin are restricted to retinal photoreceptors and a class of pinealocytes derived from photoreceptor cells, the occurrence of these proteins in certain tumor cells of medulloblastomas suggests a differentiation of these cells along the photoreceptor cell lineage and allows the identification of a special subtype of medulloblastoma displaying photoreceptor-specific characteristics. This subtype appears to be closely related to retinoblastomas and pineal cell tumors. The incidence of this subtype corresponds to approximately 30% of all medulloblastomas. Correlation between the demonstration of immunoreactive S-antigen and rod-opsin and the course of the disease revealed a 10-year survival rate of 50.6% for patients with medulloblastomas displaying photoreceptor-specific characteristics and maximally 11% for patients suffering from medulloblastomas devoid of these markers. Although the statistical evaluation does not provide a significant result, the estimatedP-value of 0.085 indicates a distinct trend toward a better prognosis for patients suffering from medulloblastomas with photoreceptor-specific features. The validity of this trend needs to be proven in further studies with a greater number of patients.
    Type of Medium: Electronic Resource
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  • 12
    ISSN: 1432-0533
    Keywords: Medulloblastoma ; Retinal ; Rod-opsin ; S-Antigen ; Photoreceptor cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of the present study was to evaluate the putative photoreceptor differentiation found in certain cerebellar medulloblastomas. The analyses were focussed on S-antigen, rod-opsin (the apoprotein of the visual pigment rhodopsin) and 11-cis retinal (the prosthetic group of rhodopsin). Fresh frozen and paraffinembedded biopsy specimens of three medulloblastomas were investigated by means of immunocytochemistry, enzyme-linked immunosorbent assay (ELISA), high-pressure liquid chromatography (HPLC), and immunoblotting. As shown in paraffin sections, one out of the three tumors (tumor A) contained S-antigen- and rod-opsin-immunoreactive tumor cells. The immunoblotting technique revealed in this tumor a single protein band of approximately 48–50 kDa that reacted with the S-antigen antibody and three protein bands of approximately 40, 75 and 110 kDa recognized by the rod-opsin antibody. These bands could not be detected in the two remaining tumors (tumor B and C). The rod-opsin content of tumor A was quantified by the ELISA; 11.7 pmol rod-opsin were calculated for the biopsy. The HPLC demonstrated the presence of 11-cis- and all-trans-retinal in tumor A, but not in tumors B and C. Furthermore, it was shown that 11-cis-retinal was converted to all-trans-retinal upon illumination of the tumor extract. The ratio between 11-cis-and all-trans-retinal was approximately 1:1 before illumination and 3:5 after illumination. A total of 2–3 pmol of retinal was found in the biopsy of tumor A. In addition all-trans-retinol was present in this tumor. The results indicate that certain medulloblastomas express a functional photopigment and S-antigen, another protein of the phototransduction cascade. They strongly support the concept that medulloblastoma cells may differentiate along the photoreceptor cell lineage.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 83 (1992), S. 308-314 
    ISSN: 1432-0533
    Keywords: Large T-antigen ; Transgenic mice ; Pineal cell tumors ; Pineal organ ; Primitive neuroectodermal tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Adult transgenic mice expressing the large T-antigen of the Simian virus 40 (SV 40) under the control of the Moloney murine sarcoma virus (MSV) enhancer and the SV 40 promoter develop inheritable uniform midline brain neoplasms showing features of primitive neuroectodermal tumors. The origin and histogenesis of these tumors were investigated in the present study. The brain and pineal organ of fetal and young transgenic mice less than 3 months old displayed normal macroscopic and microscopic features. In 3.5-month-old animals, the pineal organ was considerably enlarged due to hyperplasia, finally leading to tumor formation. Immunocytochemical demonstration of large T-antigen showed that this oncoprotein was already expressed in the nuclei of certain cells in the pineal organ of fetuses (16 and 18 days old) and newborn animals, but was absent from all other parts of the brain. The immunocytochemical demonstration of S-antigen (arrestin), a highly characteristic marker for pinealocytes, was used for further characterization of the large T-antigenimmunoreactive cells. The fetal pineal organ did not contain immunoreactive S-antigen. This first occurred in certain pinealocytes of newborn mice. Double immunostaining revealed that in newborn and older transgenic mice the immunoreactive large T-antigen was exclusively found in nuclei of cells containing S-antigen immunoreaction in their cytoplasm. Thus, transformed pinealocytes appear as stem cells of the experimental tumors. The results of this study suggest that primitive neuroectodermal tumors and the normal tissue from which they originate share certain molecular and immunocytochemical features.
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  • 14
    ISSN: 1432-0533
    Keywords: Interphotoreceptor retinoid-binding protein (IRBP) ; Medulloblastoma ; Retinoblastoma ; Pineocytoma (-blastoma)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previously, immunoreactive rod-opsin and S-antigen (arrestin), two highly characteristic markers of retinal photoreceptors and pinealocytes, were shown to be present in certain medulloblastoma cells. It, thus, has been suggested that such cells differentiate along the photoreceptor lineage. This is corroborated in the present immunocytochemical investigation using antibodies against another photoreceptor-cell marker, the interphotoreceptor retinoid-binding protein (IRBP). As shown in preparations of human retina and pineal organ, IRBP can be successfully demonstrated in formalinfixed and paraffin-embedded tissue: the IRBP immunoreaction is located to the outer and inner segments of retinal photoreceptor cells and to perikarya of certain pinealocytes. Examination of formalin-fixed, paraffinembedded biopsy specimens of 66 cerebellar medulloblastomas revealed varying numbers of IRBP-immunoreactive tumor cells in 19 cases that were formerly shown to contain rod-opsin and S-antigen immunoreaction. IRBP-immunoreactive tumor cells were also found in a retinoblastoma and a pineocytoma, but not in neuroblastoma, ganglioneuroblastoma, glioblastoma, oligodendroglioma and astrocytoma. The results indicate: (1) cerebellar medulloblastomas are heterogeneous in their differentiation potential; (2) one type of medulloblastoma displays photoreceptor characteristics; (3) this type appears to be closely related to retinoblastoma and pineal cell tumors; and (4) all three types of tumors may display additional common features to be explored in future studies.
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  • 15
    ISSN: 1432-0533
    Keywords: Key words Oligodendroglioma ; Grading ; MIB-1 nuclear labeling index ; Vimentin ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Histopathological, immunohistochemical and clinical parameters were correlated with survival in 89 cases of oligodendroglioma (65 patients with grade II and 24 patients with grade III of the WHO classification). Median survival time and 5-year survival rate were 3.5 years and 76% for patients with oligodendroglioma grade II and 0.875 years and 23% for patients with oligodendroglioma grade III. The tumor biopsy specimens were immunohistochemically analyzed for Ki 67 (MIB-1), vimentin, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE) and synaptophysin. MIB-1 nuclear labeling index ranged from 0.0% to 33.4%; vimentin-immunoreactive tumor cells were found in 25 cases. MIB-1 nuclear labeling index and vimentin immunoreaction showed a significant statistical correlation to the 5-year survival rate of the patients. Tumors with vimentin expression (n = 25) and/ or high MIB-1 labeling index (n = 26) had a poorer prognosis than tumors lacking vimentin expression (n = 57) and/or displaying a low MIB-1 labeling index (n = 56). The expression of immunoreactivity for GFAP (n = 53), NSE (n = 23) and synaptophysin (n = 15) appeared to be of no prognostic relevance. Patients with gross total tumor resection (n = 47) had a median survival time and 5-year survival rate of 3.3 years and 84% compared to 1.2 years and 42% for patients with subtotal resection (n = 41). The comparison between patients who underwent surgery alone (n = 53) and those who had surgery plus postoperative radiation therapy showed no significant survival benefit from postoperative radiation therapy. In conclusion, tumor grade, MIB-1 labeling index, expression of vimentin and the extent of surgery are shown to be of prognostic relevance for patients with oligodendroglioma.
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  • 16
    ISSN: 1432-0533
    Keywords: Key words Pineal parenchymal tumors ; Neuronal ; differentiation ; Tryptophan hydroxylase ; Serotonin ; N-acetyltransferase ; Hydroxyindole-O-methyltransferase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using both tumor specimen and cultured tumor cells, we have studied the differentiation of a pineocytoma by light and electron microscopy (EM) and immunohistochemical demonstration of glial, neuronal and neuroendocrine markers. Only interstitial cells were labeled with anti-glial fibrillary acidic protein and anti-S100 protein antibodies. Synaptophysin, neurofilaments and tau labeling was found in cells forming the pineocytomatous rosettes. Some cells also bound the anti-tryptophan hydroxylase antibody (TPOH), but no staining was seen after application of anti-chromogranin A or S-antigen antibodies. EM provided evidence for neurosensory differentiation demonstrating the presence of vesicle-crowned rodlets, cilia (9+0) and fibrous filaments. In culture, tumor cells proliferated slowly and showed positive immunolabeling for vimentin and TPOH. Expression of mRNA coding for TPOH, serotonin N-acetyltransferase, hydroxyindole-O-methyl-transferase and c-myc was found in the tumor using reverse transcriptase-polymerase chain reaction. These results demonstrate neuronal differentiation of this pineocytoma and suggest that the neoplastic pineal cells are capable of synthesizing serotonin and melatonin.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 69 (1986), S. 165-167 
    ISSN: 1432-0533
    Keywords: Pineocytoma ; Immunocytochemistry ; S-antigen ; Polyclonal antibody
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A pineocytoma was investigated by means of immunocytochemistry with the use of a polyclonal antibody against bovine retinal S-antigen. Several cells of this tumor displayed strong S-antigen-like immunoreaction in analogy to certain pinealocytes in normal human pineal organs. This study indicates that S-antigen immunocytochemistry may be applied to characterize tumors of the pineal region.
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  • 18
    ISSN: 1432-0533
    Keywords: Key words Oligodendroglioma ; Neurofilament ; Glial fibrillary acidic protein ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have characterized a new polyclonal antibody against heavy chain (H) of neurofilament which can be used to demonstrate neurofilament H in normal brain tissue and oligodendroglioma cells immunocytochemically and immunochemically. Using this antibody we found neurofilament H-immunoreactive tumor cells in 13 oligodendrogliomas (6 WHO grade II, 7 WHO grade III) out of 84 oligodendrogliomas investigated (59 WHO grade II and 25 WHO grade III). Double immunolabeling and confocal laser scanning microscopy showed colocalization of neurofilament H and glial fibrillary acidic protein in certain oligodendroglioma cells. Colocalization of neurofilament and synaptophysin was observed only rarely. The results support the notion that oligodendrogliomas consists of a heterogeneous cell population displaying various stages of differentiation and dedifferentiation. The occurrence of neurofilament H-immunoreactive tumor cells in oligodendrogliomas is not related to the survival of the patients.
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  • 19
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Immunocytochemical double-labeling methods are important tools in cell and neurobiology. Here we describe a method which is based on double immunofluorescence and allows specific detection of two different antigens located in the same cell compartment by two primary antibodies raised in the same species. As an example, we present the double-immunolabeling method for the S-antigen (SAg), a photoreceptor-specific protein, and the indoleamine serotonin (5HT) in dissociated trout and rat pineal cells immobilized on coversliped and in frozen sections of the trout pineal organ. As a first step, the preparations on the slides or coverslips were sequentially incubated with the first primary antibody (rabbit anti-SAg), the fluorescein-labeled (anti-rabbit) secondary antibody, and then with normal rabbit serum. Meanwhile, the second primary antibody (rabbit anti-5HT) was coupled to a Cy3-labeled secondary (anti-rabbit) antibody in a reaction tube and excess binding sites were quenched with normal rabbit serum. This complex was applied to the specimens after completion of the first (SAg) immunoreaction on the slide. For control experiments, the first (anti-SAg) or the second (anti-5HT) primary antibody were omitted. Most of the rat and trout pinealocytes were double immunolabeled for SAg and 5HT. In the trout, few cells contained SAg or 5HT immunoreaction only. This underlines the selectivity of each immunoreaction. The results show that the method can be used for the analysis of whole cells and tissue sections by means of conventional fluorescence and confocal laser scanning microscopy.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 239 (1985), S. 599-610 
    ISSN: 1432-0878
    Keywords: Pineal organ, Salmo gairdneri ; Pinealocytes ; Blood-brain barrier ; Tracer studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The problem of the blood-brain barrier in the pineal organ of the rainbow trout, Salmo gairdneri, was investigated following intraperitoneal or intracardial injections of several tracers and dyes with different molecular weights. As demonstrated at the light-microscopic level, repeated injections of trypan blue or horseradish peroxidase (HRP) resulted in an accumulation of these substances in the pineal epithelium (parenchyma). By use of the electron microscope, HRP was found in electron-dense bodies, probably lysosomes, in (i) the endothelial cells and perivascular macrophages 4 h after intraperitoneal injection, (ii) the supporting cells and intrapineal or luminal macrophages 8 h after injection, and (iii) the receptor cells 24 h after injection of the tracer. Ferritin particles penetrated the fenestrated endothelium of pineal capillaries. They were confined to vesicles, vacuoles and the smooth endoplasmic reticulum of the supporting cells as well as to the synaptic vesicles and the smooth endoplasmic reticulum of the pineal photoreceptors. The intercellular passage of tannic acid mixed with the fixative was blocked at the luminal junctional complex separating the pineal lumen from the basal portion of the pineal epithelium. The passive intercellular transport of substances with high molecular weight from the bloodstream to the cerebrospinal-fluid compartment is thus prevented. However, no blood-brain barrier exists for exogenously administered proteins, which are rapidly taken up by pineal cells and actively transported in a transcellular manner. The findings on the blood-brain barrier of the pineal organ of the rainbow trout are discussed with particular reference to the endocrine capacity of pineal sensory organs.
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