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S Patt

Publications and source records attributed to S Patt.

At least 37 records · Page 2Linked to original sources
PubMed1998

Glutamate receptor activation can trigger electrical activity in human glioma cells.

Cells from major types of gliomas, i.e. oligodendrogliomas and glioblastomas, are able to generate action potentials upon a current injection similar to neurons (Patt et al. (1996) Neuroscience, 71, 601-611; Labrakakis et al. (1997b) J. Neuropath. Exp. Neurol., 56, 243-254. Here, we report that activation of ionotropic glutamate receptors by the selective agonist, kainate, or by glutamate itself, depolarized the tumour cells in culture and living slices from tumour tissue, and can elicit volleys of action potentials, as recorded with the patch-clamp technique. Sixty-six percent of the glioblastoma cells, 44% of the astocytoma and 86% of the oligodendroglioma cells responded to glutamate and the specific agonist of AMPA/kainate receptors, kainate. The involvement of non-NMDA (N-methyl-D-aspartate) receptors is further supported by the observation that both kainate and glutamate currents were blocked by CNQX (6-cyano-7-nitroquinoxaline-2,3-dione). The receptor activation was accompanied by an increase in cytosolic Ca2+, as recorded with a fura-2 microfluorometric system. The Ca2+ elevation was mediated by the activation of Ca2+ channels due to membrane depolarization. The presence of voltage-gated Ca2+ channels was confirmed by patch-clamp experiments. Taken together, these findings imply that the electrophysiological properties of glioma cells are more reminiscent of those of neurons than of glial cells.

Calcium↗
PubMed1997

Autocrine interleukin-1 receptor antagonist can support malignant growth of glioblastoma by blocking growth-inhibiting autocrine loop of interleukin-1.

In situ hybridization (ISH) of human glioblastoma tissue sections revealed expression of interleukin-1 (IL-1)alpha and/or beta and IL-1 receptor types I and II (IL-1R I and II) in the majority of cases evaluable. To understand the function of IL-1-family members in human glioblastomas, we have studied 6 glioblastoma cell lines. RT-PCR, ISH, ELISA and 125I-IL-1-binding assays revealed expression of IL-1 and high-affinity receptors for human (h)IL-1 in all but 1 cell line. Using a colony growth assay in semi-solid media for testing serial plating efficacy (PE, number of colonies per number of cells seeded in %), only the IL-1R-negative cell line was not influenced by recombinant human (rh)IL-1alpha or -beta, whereas IL-1 down-regulated the self-renewal of clonogenic cells of the other glioblastomas. Tritiated thymidine uptake was down-regulated by rhIL-1 in all cell lines studied. Cell viability remained unchanged by rhIL-1. Wherever growth modulation by rhIL-1 was detected, it could be reversed by either soluble IL-1R I or II or by rhIL-1 receptor antagonist (ra). IL-1ra not only was able to reverse rhIL-1-induced growth modulation but alone could modulate glioblastoma growth in comparison with control in cell lines producing IL-1. Our results show the presence of public autocrine loops for IL-1 leading to growth inhibition in some glioblastomas. To understand these loops, we have studied expression and function of IL-1ra in glioblastomas. ISH of human glioblastoma tissue sections revealed expression of hIL-1ra in all 8 cases evaluable. In 4 of 6 cell lines, IL-1ra was found in the supernatant under constitutive conditions, the IL-1R-negative line being among the 2 non-producers. The other non-producing cell line, HTB 17, showed expression of hIL-1R II. Most interestingly, a neutralizing antibody against IL-1ra down-regulated growth of IL-1- and IL-1ra-producing glioblastoma cells to approx. 30% of the controls. Thus, public autocrine loops for IL-1 in human glioblastomas exist and result in growth inhibition. An autocrine production of IL-1-antagonizing molecules such as IL-1ra by these tumors can counteract this IL-1 function and represent a basic escape mechanism supporting malignant growth in some glioblastomas.

Binding Sites↗
PubMed1997

Neuroligand-triggered calcium signalling in cultured human glioma cells.

Cells from primary cultures of four glioblastomas (GB), three low-grade astrocytomas (A), and four low-grade oligodendrogliomas (O) were tested for the presence of neuroligand receptors linked to Ca2+ signalling by calcium imaging. Cells of days 3 to 21 in culture were incubated with 5 microM fluo-3-acetomethylester in a bath solution and stimulated with 0.1 mM ATP, 0.01 mM angiotensin II, bradykinin, histamine, norepinephrine, serotonin, and substance P for 15 s, with 0.01 mM glutamate and 50 mM K+ for 30 s. Changes in the Ca2+ concentration were measured with a confocal laser scanning microscope. In all glioma subtypes, the majority of cells showed Ca2+ responses after application of histamine (60% of cells tested in GB, 67% in A, 86% in O), bradykinin (66% in GB, 29% in A, 55% in O) and ATP (48% in GB, 70% in A, 47% in O). The other stimuli induced Ca2+ transients in a smaller proportion (between 33% and 2%) of the cells. Our study demonstrates that histamine, bradykinin and ATP are potent inducers of [Ca2+]i signals in gliomas.

Adenosine Triphosphate↗
PubMed1997

Cerebral angiogenesis triggered by severe chronic hypoxia displays regional differences.

The blood vessels in the brains of adult rats subjected to chronic normobaric hypoxia and control animals housed under normoxic conditions were morphometrically studied. Hypoxic male inbred Wistar rats were exposed over a period of 130 days to decreasing amounts of oxygen starting from 21% down to 7% (15%: 15 days; 12%, 10%, 8%: 22 days, respectively; 7%: 49 days). Areas of cerebral cortex, striatum, hippocampus, cerebellum, and medulla oblongata were investigated. The ratio vessel number per mm2 tissue and the average vessel size were measured using a Quantimet Q570. In the hypoxic animals, cerebral cortex, striatum, and hippocampus showed a significant increase of the vessel density per mm2 tissue (P < 0.01 or P < 0.05). The differences in both groups were highest in the striatum and hippocampus. In the cerebellum and the medulla oblongata of hypoxic animals, only a tendency to higher vessel numbers per mm2 tissue was found. The average blood vessel size differed only in the cerebral cortex and the cerebellum, but not in the other brain regions tested. The results indicate that the adaptation of the brain circulation to hypoxia is achieved by both angiogenesis and dilatation of microvessels, and that the pattern of the microcirculatory changes is not homogenous in all regions.

Animals↗
PubMed1997

Action potential-generating cells in human glioblastomas.

We studied the electrophysiological properties of cells from human glioblastomas obtained after surgery. The membrane currents were compared in cells of acute tissue slices and primary cultures using the whole cell mode of the patch-clamp technique. Very strikingly, in about a third of the tumor cells in situ and in vitro, depolarizing voltage steps elicited large, tetrodotoxin-sensitive inward currents with a threshold of about -30 mV, indicating the presence of voltage-gated sodium channels. In addition, three types of potassium currents, a delayed rectifying, an A-type, and an inward rectifying, were observed. Such a set of voltage-gated channels is characteristic for neurons. Indeed, in these glioblastoma cells, depolarizing current pulses in the current clamp mode were able to generate action potentials with properties similar to those observed in neurons. We interpret this finding as the ability of glioblastoma cells to acquire neuronlike properties but retain some glial features, since they still express markers typical for astrocytes and their precursors. The role of sodium channels in glioblastoma cells is unclear at this moment and needs further investigation. Our findings, however, imply that the tumor tissue can be intrinsically excitable and that neoplastic glial cells themselves may be an etiologic factor for epileptic seizures.

Action Potentials↗
PubMed1997

p53 mutation and protein alteration in 50 gliomas. Retrospective study by DNA-sequencing techniques and immunohistochemistry.

Alterations of the p53 protein, which is a 53 kD phosphoprotein and gene product of the p53 gene, has been found to play a major role in the genesis of a variety of human malignancies including tumors of the central nervous system. We investigated 50 tumor specimens from primary central nervous system neoplasms. Tissue samples were screened for mutations by the single-strand conformation polymorphism method and detected mutations were sequenced. All tissue specimens were stained immunohistochemically for p53 protein, which when altered accumulates in the nucleus due to prolonged half-life. Mutations were found in six cases, including one pilocytic astrocytoma World Health Organization (WHO) grade I, two astrocytomas WHO grade II, two anaplastic astrocytomas WHO grade III, and one primitive neuroectodermal tumor (PNET). In terms of relative frequency mutations were found mostly in the group of anaplastic astrocytomas WHO grade III. Interestingly, no mutations were found in the group of investigated glioblastomas. P53 immunopositivity did not correlated with the mutations found, whereas the staining index was significantly higher in the cases with detected mutations than in those without. When p53 alterations is seen as an indicator for different pathogenic pathways in glioma formation, this study gives evidence for a difference between anaplastic astrocytoma and glioblastoma. However, since there was a great overlap in p53 immunopositivity and p53 mutation in tumors of different WHO grades and entities, it seems that p53 will not act as a marker molecule neither for tumor entities nor for tumor malignancy.

Central Nervous System Neoplasms↗
PubMed1996

Human central neurocytoma cells show neuronal physiological properties in vitro.

Central neurocytoma is a rare brain tumor composed of small round synaptophysin-positive cells, suggesting a neuronal origin of these tumor cells. Glial properties are inferred, however, from the observation that the tumor cells exhibit a strong morphological similarity to oligodendroglioma cells and show an astrocytic differentiation in vitro. To test for neuronal or glial physiological properties, we studied cultured neurocytoma cells derived from a surgical specimen from a 44-year-old man, employing the patch-clamp technique. Early primary cultures were composed of morphologically unique bi- or multipolar cells which were positive for synaptophysin and negative for the astrocyte marker glial fibrillary acidic protein. In the majority of these cells, whole-cell membrane current recordings revealed physiological properties of neurons, i.e., a high density of Na+ currents, the capacity to generate action potentials, and the expression of inotropic neurotransmitter receptors. Metabotropic neurotransmitter receptors could be demonstrated by Ca2+ imaging techniques. The remaining bi- or multipolar cells and almost all cells in later culture stages and in vitro passage lacked these neuronal properties and showed physiological features characteristic of glial cells. We conclude that the major population of neurocytoma cells shows physiological properties of neurons and that with time in culture this population is replaced by electrically passive cells.

Action Potentials↗
PubMed1996

Neuron-like physiological properties of cells from human oligodendroglial tumors.

One of the most common symptoms of patients with oligodendrogliomas is the high frequency of epileptic seizures. We thus studied the physiological properties of cells in six human oligodendrogliomas and two oligoastrocytomas obtained from surgical material. The majority of tumor cells in living brain slices can generate action potentials as recorded with the patch-clamp technique indicating that this tissue is dominated by electrically excitable cells. In cultures from the same material, the action potential generating cells prevail within the first days and are subsequently replaced by electrically inexcitable cells. From histopathological and immunohistochemical data, the histogenesis of human oligodendroglial tumor is still uncertain. Our physiological study has not settled the debate on the origin of these tumors but revealed important findings with regard to this question. Since action potential generating glial cells have not been described in situ so far their occurrence in oligodendroglial tumors implies that oligodendroglial tumor cells may belong to the neuronal cell lineage.

Adult↗
PubMed1996

p53 gene mutations in human astrocytic brain tumors including pilocytic astrocytomas.

Recent molecular biological studies have shown evidence for a distinct pathogenesis of pilocytic astrocytomas based on alterations other than mutations of the tumor suppressor gene p53. To prove these data, the authors screened a series of 42 astrocytic human brain tumors with a relatively high proportion (16.6%) of the pilocytic variant for the presence of p53 mutations, using the polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis, followed by DNA sequencing. Mutations were found in one of seven (14.3%) pilocytic astrocytomas, in one of 18 (5.6%) low grade astrocytomas, and in one of four (25%) anaplastic astrocytomas, but in none of 13 glioblastomas. Sites of missense mutations were in exon 8 (codons 281 and 282), and exon 5 (codon 151). Silent mutation was found in exon 9 (codon 324), which was related to pilocytic astrocytoma. This is, to the authors' knowledge, the first report that shows a p53 mutation in pilocytic astrocytomas. However, the p53 mutation was only found in one of seven tumors of this entity and was a silent mutation, which does not lead to change of amino acids. Thus, the significance of this alteration for the development of this special tumor type seems to be low. Nevertheless, it may be a sign of genetic instability and is thus suggested to be of certain pathogenetic relevance. The p53 findings concerning the other tumors are in accordance with the view of p53 gene mutations to be early events in astrocytoma formation.

Adolescent↗
PubMed1996

Clear cell meningioma: report of a spinal case.

A sacrococcygeal case of clear cell meningioma in a 38-year-old man is reported. Compared to the seven spinal clear cell meningiomas described so far, this case demonstrated the highest recurrency rate. Multiple recurrences were most likely due to the extensive infiltrative growth pattern of the tumor hindering complete microscopic surgical resection. Histologic parameters were not relevant to predict recurrences, since cellular anaplasia was lacking and growth fraction was low in the first operation and all subsequent recurrences. In view of what is now known of clear cell meningiomas, the tumor showed all histologic and immunohistochemical features which are typical for this tumor entity. However, the tumor was first diagnosed by capable pathologists and neuropathologists as fibroma-like mesenchymal tumor, metastatic renal carcinoma, chordoma, chondroma untypical osteosarcoma, and microcystic meningioma. Correct diagnosis was made by electron microscopy which has revealed comparable findings to those of other rare electron microscopical cases reported so far; high content of cytoplasmic glycogen diffusely distributed throughout the cytoplasm or aggregated within vacuoles, intermediate filaments, desmosomes, interdigitation of cell membranes and large amounts of collagen fibers, some of which were of the giant amianthoid type. Since meningiomatous features of clear cell meningiomas are not obvious light microscopically and the tumors may be confused with nonmeningiomatous neoplasms, electron microscopical investigation is highly recommended in each case of suspected clear cell meningioma.

Adult↗
PubMed1994

AgNOR- and PCNA-studies in astrocytomas of the optic nerve.

Nine pilocytic astrocytomas of the optic nerve were investigated with the AgNOR method and by immunohistochemistry with anti-PCNA antibodies. Four patients were male, 5 female (mean age 16.5 years, range 1-55 years). Seven pilocytic astrocytomas were low-grade tumors (grade I, WHO [2]), one tumor contained giant cells and prominent nuclei (grade II), the remaining tumor was anaplastic (grade III). In each case, 5 randomly chosen areas were investigated by light microscopy using objective 40. The PCNA staining index was defined as number of positive tumor cell nuclei divided by the total amount of tumor cell nuclei in the microscopic field. Tumors showing only one immunopositive cell nucleus at low magnification were considered to have a staining index below 0.1%. The staining index of the 7 grade I tumors was below 0,1%, the grade II tumor showed a staining index of 1%, and the anaplastic astrocytoma (grade III) demonstrated a 2.5% staining index. Investigations with the AgNOR method confirmed the above results of a low growth fraction in grade I-III grade astrocytomas of the optic nerve. Though low growth fractions have been reported in anaplastic astrocytomas and glioblastomas of the cerebrum, the low staining index in the anaplastic pilocytic astrocytoma of our series is remarkable: Instead of histological parameters like cellular and nuclear polymorphism and cellular density, the growth fraction could be a better parameter for the clinical course, which has in fact been benign in this case of an anaplastic pilocytic astrocytoma of the optic nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

A Golgi study on the red nucleus in man.

The different cell types comprising the human red nucleus (RN) from eight patients without neuronal diseases were investigated using the Golgi-Braitenberg method for long-stored autopsy material. No giant cells were found due to regression of the magnicellular part of the human RN. We found larger (40-50 microns) and smaller (30 microns perikaryon size) medium-sized multipolar neurons with long dendrites, mushroom spines and typical distal dendritic tufts. The larger medium-sized RN neurons had some brush-shaped dendritic end portions which could not be observed in the Golgi studies on various other mammals described in the literature. We additionally found small neurons with a perikaryon size of 15 microns. These cells were thought to be intrinsic neurons similar to those in animal investigations. The neuronal types found in the normal human RN corresponded to those in the parvicellular part of the mammalian RN. Dendritic end brushes, however, are typical only for the human RN.

Aged↗
PubMed1993

[Prenatal diagnosis of fetal polymicrogyria--case report].

Migration disorders of foetal neurons are rare conditions which are normally diagnosed after birth and may be followed by severe alterations of neurological development. We describe a case of foetal hemilateral polymicrogyria in combination with hemihypoplasia of the brain, the symptoms of which were diagnosed in the 23rd week of pregnancy, leading to termination of pregnancy. To the best of our knowledge, this is the first case report of antenatal diagnosis of this disorder by vaginal sonography.

Abortion, Eugenic↗
PubMed1993

Venous angioma with papillary endothelial hyperplasia in the superior orbital fissure.

We present the case of a 27-year-old woman with a vascular malformation localized in the superior orbital fissure. Histological diagnosis was that of a venous angioma with papillary endothelial hyperplasia. The lesion was removed completely via an intradural approach to the superior orbital fissure with subsequent recovery of the neurological deficits. To the best of our knowledge, no such case has been reported so far in the literature. The radiological, intraoperative, and histopathological findings are presented and discussed with respect to the literature.

Adult↗
PubMed1993

Nucleus pulposus regeneration after chemonucleolysis with chymopapain?

Chemonucleolysis was unsuccessful in 100 out of 519 patients with herniated lumbar discs treated within a period of 3 years. These patients were subsequently submitted to open surgery. Disc material from 88 of the 100 patients was examined by light microscopy (hematoxylin and eosin, van Gieson's, Nissl's and periodic acid-Schiff staining) to verify the effect of enzymatic activity compared to the histologic findings in a similar control group. In 84 of the 88 cases, signs of enzymatic activity were revealed by eosinophilia of the ground substance, altered Nissl staining and positive periodic acid-Schiff reaction within the chondrocyte halos. These alterations indicate that the enzyme was active and confirm the results of previous studies with smaller numbers of cases. Histologic alterations were quantified according to the intensity and extent of staining. The signs of enzymatic activity were significantly (P < 0.01) stronger after short time intervals between chemonucleolysis and surgery than after long intervals. These findings may be interpreted as indicating a regenerative potential of the nucleus pulposus.

Adult↗
PubMed1993

A Golgi study of human locus coeruleus in normal brains and in Parkinson's disease.

The locus coeruleus (LC) of eight adults without neurodegenerative disease and eight patients with Parkinson's disease was investigated by means of the Golgi-Braitenberg method for formalin-fixed human autopsy material. As with Golgi studies in the rat and cat, two main neuronal classes could be demonstrated in the human LC: (i) medium-sized fusiform and multipolar LC neurons known to contain neuromelanin and (ii) smaller neurons of widely varying somatic shape and dendritic arborization which are considered to be intermingled neurons of adjacent brain stem nuclei not containing neuromelanin. In Parkinson's disease, the Golgi-impregnated medium-sized LC neurons were reduced in number. They showed marked reduction of dendritic length, severe loss of spines, dendritic varicosities and swollen perikarya. The last two findings could be due in part to Lewy-body inclusions. The smaller non-noradrenergic neurons did not show severe pathological changes by the Golgi impregnation technique, which is in line with the fact that only neuromelanin-containing LC neurons are affected in the pathological process of Parkinson's disease.

Aged↗