Search PubMed⌕ Search

Biomedical subjects

W Paulus

Publications and source records attributed to W Paulus.

At least 217 records · Page 12Linked to original sources

Basement membrane invasion of glioma cells mediated by integrin receptors.

Basement membrane invasion precedes meningeal dissemination and systemic metastasis of glioma cells. In order to investigate the invasive ability of glioblastomas and the functional role of extracellular matrix receptors, the authors performed in vitro invasion assays where the number of cells was determined from freshly resected tumors (primary cultures and fifth passages) and from cell lines (U-138 MG, U-373 MG, and GaMg) that had migrated through a filter coated with a reconstituted basement membrane (Matrigel). The involvement of integrin adhesion molecules was examined by preincubation of glioma cells with blocking antibodies to specific integrin chains. Cells from all of the glioblastomas had migrated through the Matrigel after 4 to 24 hours; the number of invasive cells was highest in the cell lines. Invasion of U-138 MG cells was reduced with antibodies to alpha 7, alpha v, beta 1, and beta 3 integrin chains and markedly increased by anti-alpha 5, while invasion of U-373 MG cells was reduced by antibodies to alpha 3, alpha v, beta 1, and beta 3 and increased by anti-alpha 6. It is concluded that: 1) glioma cells are able to penetrate Matrigel, indicating that the basement membrane is not a resistant barrier for infiltrating cells; and 2) basement membrane invasion is mediated by integrins in a complex manner. Some integrins promote while others inhibit basement membrane invasion. Furthermore, the integrins involved may differ between various glioma cells.

Antibodies↗

[Increased amounts of IL-10 mRNA in anaplastic astrocytomas and glioblastoma multiforme].

Interleukin 10 (Il-10) was initially discovered on the basis of its ability to suppress cytokine synthesis. Additionally, it can exert immunosuppressive effects on a variety of cell types. Since patients with malignant gliomas present with a general impairment of the immune system, we sought to investigate if IL-10 is expressed in the glioma tissue. Using RT-PCR, IL-10 mRNA levels were determined in 37 glial tumors of different grades including 2 recurrencies, 3 specimens from normal brain tissue and 3 glioblastoma cell lines. Expression of IL-10 mRNA was demonstrable in all tumors as well as in normal brain. High grade tumors and recurrent cases expressed significantly higher amounts of IL-10 specific mRNA compared to low grade tumors, while 2 out of 3 cell lines showed only weak constitutive expression. We suggest, that IL-10 may contribute to the progression of astrocytomas by allowing the tumor cells to attenuate the T-cell immune response and evade immune detection.

Autopsy↗

Microglial reaction in Pick's disease.

Number and morphology of microglial cells (MC) were compared in 6 cases each of Pick's disease (PD), Alzheimer's disease (AD) and controls using immunohistochemistry with the monoclonal antibody Ki-M1P. The severely involved neocortex of both PD and AD, and in particular the white matter subjacent to spongy PD lesions showed a marked increase of MC density, whereas non-affected PD areas and AD white matter showed no MC changes. The PD hippocampus, particularly the dentate gyrus, showed reduction of MC density and processes. We conclude that (1) MC reaction represents a major element of PD histopathology, and (2) density, morphology and distribution of MC are different in AD and PD.

Aged↗

The use of immunomorphology to differentiate choroid plexus tumors from metastatic carcinomas.

BACKGROUND: The histologic and immunohistologic differential diagnosis of choroid plexus papillomas/plexus carcinomas (PP/PC) versus metastatic carcinoma in the brain is problematic. METHODS: Thirty-four choroid PP/PC from 28 patients, 5 normal choroid plexus, and 45 cerebral metastatic carcinomas were immunohistochemically examined with the monoclonal anti-epithelial noncytokeratin antibodies HEA 125 and Ber EP4 using the alkaline phosphatase anti-alkaline phosphatase (APAAP) method. RESULTS: Normal choroid plexus epithelium was consistently negative. Sections from PP/PC of 3 of 28 patients demonstrated immunoreactivity for these antibodies. In contrast, 43 of 45 cerebral metastatic carcinomas displayed positive immunostaining for HEA 125, and 44 of these 45 carcinomas were positive for Ber EP4. Thus, sensitivity was higher for these antibodies than for the monoclonal anticytokeratin antibody KL1 (41/45). All three HEA 125/Ber EP4-positive PP/PC contained periodic acid-Schiff (PAS)-positive, tall columnar tumor cells. The intensively HEA 125, Ber EP4, and PAS-positive PP/PC were interpreted as possible transitional forms of the mucus-secreting and acinar PP/PC: CONCLUSIONS: Despite this restriction, the authors proposed the application of HEA 125 and Ber EP4 as a reliable tool in the differential diagnosis of PP/PC versus metastatic carcinoma, especially in combination with glial fibrillary acid protein and transthyretin. Currently, all HEA 125/Ber EP4-positive PP/PC in patients older than 20 years proved to be metastatic carcinomas during their clinical course.

Adolescent↗

The time course and location of cerebral evoked activity associated with the processing of colour stimuli in man.

Area V4 has been located in man in the region of the fusiform gyrus on the inferior surface of the occipital lobe. Using multiple dipole source analysis on multichannel EEG recordings of visual evoked potentials to coloured 'Mondrian' stimuli in man, we have confirmed that activity is consistently seen in this area regardless of the retinal area stimulated and have obtained new information concerning its time course. Three different localized centres of activity follow the visual stimulus, with peak latencies of 90, 110 and 160 ms, and arising respectively in the region of visual areas V1, V2/V3 and V4. The time course and character of the V4 dipole activity to a colourless black-and-white Mondrian is indistinguishable from that to the coloured Mondrian, supporting the evidence that the cells of V4 are not exclusively concerned with colour processing.

Brain Mapping↗

Impairment of retinal increment thresholds in Huntington's disease.

We have investigated detection thresholds for a foveal blue test light using a Maxwellian view system in 61 normal subjects, 19 patients with Huntington's chorea, 14 patients with Tourette's syndrome, and 20 patients with schizophrenia. Ten measurements were made: The blue test light (1 degree diameter, 500 msec duration) was presented either superimposed on a yellow adaptation field (5 degree diameter) or 500 msec after switching off this field (transient tritanopia effect). In both cases five different background intensities were presented. The only abnormality found was in patients with Huntington's chorea. During adaptation these patients' thresholds are significantly higher than normal (p < 0.005). No change was found in the transient tritanopia effect. Huntington's disease causes degeneration of several different transmitter systems in the brain. Increment threshold testing allows for noninvasive investigation of patients and confirms the involvement of the retina in the degenerative process in Huntington's chorea.

Adaptation, Ocular↗

Identification of the visual motion area (area V5) in the human brain by dipole source analysis.

The retinal periphery of nine healthy subjects was stimulated with computer-generated random-dot kinematograms. These stimuli provided almost isolated visual motion information and minimal position cues. Pattern-reversal stimuli at the same location in the visual field were used for control. Stimulus-related electrical brain activity was recorded from 29 scalp electrodes. Total mean and individual data were analyzed with a spatiotemporal multiple dipole model. The scalp potentials showed a different spatial distribution for motion and pattern stimulation in the time range of 160-200 ms. In this epoch, the predominant motion-related source activity was localized in the region of the contralateral occipital-temporal-parietal border. A significant ipsilateral source activity was not found. The predominant source activity related to the pattern stimulus occurred in the same epoch. The corresponding equivalent dipole was localized more medially and deeper in the brain. The orientation of these major dipole activities was markedly different. These dipoles appeared to represent activity of distinct extrastriate areas, in contrast to earlier activity which was modelled by more posterior dipoles in the occipital lobe. The latter dipoles were at comparable contralateral locations and had similar peak activities around 100 ms, suggesting an origin in the striate cortex.

Adult↗

Comparison of integrin adhesion molecules expressed by primary brain lymphomas and nodal lymphomas.

The expression of 17 adhesion molecules was immunohistochemically examined in 5 primary cerebral lymphomas (PCL) and in 5 histologically similar nodal lymphomas (NL) to evaluate their possible involvement in selective targeting of lymphoma cells to the brain. PCL and NL tumor cells showed very similar expression patterns: they were consistently positive for alpha 3, alpha 4 and beta 1 integrin chains; negative for alpha 1, alpha 2, alpha 6, beta 3 and beta 4 integrin chains; and heterogeneous for alpha 5, alpha L, alpha M, alpha X, beta 2 and beta 7 integrin chains, as well as for intercellular adhesion molecule-1 (ICAM-1) and the selectin LECAM-1. Loosely infiltrating PCL showed lower levels of the alpha L beta 2 integrin than compact cell clusters. Vessels stained for ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1). We conclude that the adhesion molecules implicated in the extravasation of non-neoplastic leukocytes (alpha 4 beta 1/VCAM-1 and alpha L beta 2/ICAM-1) are also expressed by both PCL and NL. The adhesion molecules examined are apparently not selective mediators of lymphoma cell homing to the brain, but at least alpha L beta 2 integrin might be related to the infiltration pattern of PCL within the brain parenchyma.

Antibodies, Monoclonal↗

Central nervous system involvement in Leber's optic neuropathy.

Six months after the onset of visual loss a 23-year-old male patient with Leber's optic neuropathy associated with a mitochondrial DNA mutation developed brain stem involvement with Parinaud's syndrome and oculopalatal myoclonus. Magnetic resonance imaging (MRI) revealed a high signal area in the brain stem, corresponding to a hypodense area in the CT scan that did not show contrast enhancement. Distinct diminution but not complete remission of the MRI findings was found in the 5-year follow-up, which was not accompanied by clinical improvement. Although the MRI findings were compatible with a demyelinating lesion, neither extensive evoked potential studies nor spinal fluid examination supported this.

Adult↗

Bereitschaftspotential in idiopathic and symptomatic restless legs syndrome.

Patients with idiopathic and symptomatic restless legs syndrome (RLS) suffer from "dyskinesia while awake" or "daytime myoclonus" when at rest preceded by sensory symptoms. In order to characterise the RLS either as reflex movement or as voluntary movement we measured movement-related cortical potentials in 5 idiopathic and 8 uraemic RLS patients. Movements from both legs were polygraphically recorded concomitantly with cortical activity 2000 msec before to 500 msec after onset of EMG activity. These data were compared with a voluntary simulation of each patient's movement pattern and with 5 age-matched controls performing dorsiflexion of the right, left and both feet. Cortical activity preceding daytime myoclonus was absent in RLS patients whereas self-initiated leg movements in patients elicited onset times (1180-1380 msec) and amplitudes of Bereitschaftspotential (readiness potential) not significantly different from readiness potentials in control subjects (P > 0.05). Lack of movement-related potentials in myoclonus and/or dyskinesias during daytime in RLS patients is compatible with an involuntary mechanism of induction and points towards a subcortical or spinal origin of RLS.

Adult↗

Bereitschaftspotential: is there a contribution of the supplementary motor area?

Bereitschaftspotentials (BPs) preceding simple repetitive finger movements were recorded in 11 normal volunteers. By modeling the recorded data with multiple equivalent dipoles we found that bilateral sources in the motor cortex were the best fitting hypothesis for the early BP. The activity of the source contralateral to the moving finger was increased during the steep slope of the late BP before and during the motor potential. Around and after electromyogram (EMG) onset, separate sources were detected for the motor potential close to the anterior wall of the central sulcus, and for the reafferent somatosensory potential in the postcentral gyrus. Their source wave forms showed short transient deflections peaking about 10 msec and 100 msec, respectively, after EMG onset. No evidence was found for significant source currents in the supplementary motor area (SMA), which has been suggested as the main generator of the BP. Placing probe dipoles arbitrarily into the region of the SMA did not result in the detection of a large source activity. Therefore, we conclude that the SMA does not provide a major contribution to the scalp BP during simple repetitive finger movements.

Adult↗

Effect of embolisation of meningioma on Ki-67 proliferation index.

The proliferation indices (PIs) were determined in 33 meningiomas using two monoclonal antibodies to the Ki-67 antigen (Ki-67 and MIB1). PIs obtained using Ki-67 on frozen material were intermediate between the lowest and highest MIB1 PIs determined in paraffin wax sections. Preoperative embolisation did not influence Ki67 PI, but four of the 15 embolised tumours showed substantially increased MIB1 PIs around embolisation necroses. Proliferation can be reliably assessed in routinely processed meningioma tissues using MIB1; and increased perinecrotic PIs may occur in embolised meningiomas without being an indication of malignancy.

Antibodies, Monoclonal↗

Transcranial magnetic stimulation (TMS) of the brain in patients with mesiotemporal epileptic foci.

Transcranial magnetic stimulation (TMS) of the human brain is mainly used for the diagnosis of diseases with disturbed central motor conduction. Recent studies revealed controversial results concerning the possibility of a TMS-induced specific activation of epileptogenic foci in patients with localization-related epilepsies, which would make TMS an additional diagnostic tool for the presurgical localization of the primary epileptogenic zone. We applied TMS to 19 patients with complex-partial seizures and investigated its effects and safety. In 12 patients we performed TMS during scalp electroencephalogram (EEG) recordings. The remaining 7 patients with localization-related epilepsies of mesiobasal limbic seizure origin underwent EEG with additionally implanted foramen-ovale-electrodes (FOE). We did not notice any significant spike activation and even observed bilateral reduction of epileptic activity in some patients. On the contrary, hyperventilation induced a marked activation of the epileptic focus. Our findings support that TMS is safe since adverse effects did not occur. However, due to possible safety hazards, TMS in epileptic patients still requires cautious application until more data will be available.

Anticonvulsants↗

Human herpesvirus-6 and Epstein-Barr virus genome in primary cerebral lymphomas.

Using dot blotting, we found Epstein-Barr virus genome in three AIDS-related primary cerebral lymphomas (PCLs), but in none of 39 sporadic PCLs. Human herpesvirus-6 sequences were present only in one sporadic PCL, as revealed by polymerase chain reaction and Southern analysis. We conclude that these viruses do not appear to play a major role in PCL pathogenesis in immunocompetent subjects.

Aged↗

Intracranial neurothekeoma (nerve-sheath myxoma). Case report.

Neurothekeoma is a benign cutaneous nerve-sheath tumor. The authors describe the case of a 16-year-old girl with a parasellar neurothekeoma that was successfully removed. Magnetic resonance imaging with gadolinium administration revealed bright enhancement of the peripheral portions and nonhomogeneous uptake in the central areas, which corresponded histologically to the vascular capsule and the myxoid center. It was concluded that: 1) intracranial neurothekeoma does exist, and 2) surgical resection appears to be the definitive therapy.

Adolescent↗

Characterization of integrin receptors in normal and neoplastic human brain.

We studied the immunohistochemical expression of integrin alpha and beta chains in the normal and neoplastic human brain. Normal astrocytes expressed alpha 2, alpha 3, alpha 6, beta 1, and beta 4 chains in some areas facing major interstitial tissues, but they were consistently negative for the other integrins examined (alpha 4, alpha 5, alpha V, alpha L, alpha M, alpha X, beta 2, beta 3). Neoplastic astrocytes in vivo and in vitro showed increased expression of alpha 3 and beta 1, and some also of alpha 5, alpha V, beta 3, and beta 4. Neoexpression of alpha 4 and reduced levels of beta 4 were detected in glioblastoma vascular proliferations compared with normal endothelial cells. Oligodendroglioma, ependymoma, choroid plexus papilloma, pituitary adenoma, and meningioma cells showed the same integrin pattern as their normal counterparts. Adhesion assays using the astrocytoma cell lines U-138 MG and U-373 MG revealed strong attachment to collagen types I to VI and undulin, which was inhibited by antibodies to beta 1, but not by those to alpha 2, alpha 3, alpha 6, and alpha V. We conclude that astrocytomas show increased levels or neoexpression of various integrins and strong attachment to various extracellular matrix components, which appears to be almost exclusively mediated by beta 1-integrins.

Antibodies↗