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Biomedical subjects

W Paulus

Publications and source records attributed to W Paulus.

At least 181 records · Page 10Linked to original sources
PubMed1996

Cardiac microembolism: prevalence and clinical outcome.

High intensity transient signals (HITS) have been identified ultrasonically in patients with extracranial vascular or cardiac disease and are suggestive of microembolic material. We studied the prevalence of these signals in 60 patients with increased risk for cardioembolic stroke and in a control group of 20 subjects. Patient groups (n = 20) were characterized by either non-rheumatic atrial fibrillation (AFIB) (I) or a history of prosthetic valve surgery with AFIB (II) or without AFIB (III). Embolic signals were not seen in the control group. In group I, 3 patients (15%) demonstrated HITS, in groups II and III 10 patients (50%). Microembolic signals in patients with prosthetic heart valves (II, III) had a higher signal intensity, indicating different embolic material. There was no correlation of microembolic signals with the anticoagulant treatment or the position of the prosthetic valve. HITS were found in 1/9 (11%) of the patients with a bioprosthetic valve as compared to 19/31 (61%) with a mechanical valve. After 6-12 months, 1 of 12 HITS positive patients had experienced a stroke and 2 had died. None of the 28 patients without HITS had suffered a stroke, 2 had died. Microembolic signals are frequent events in patients with mechanical prosthetic valves. In these patients they do not appear to be a major prognostic factor for an impending cardioembolic stroke.

Aged↗
PubMed1996

The effect of anti-epileptic drugs on visual perception in patients with epilepsy.

We investigated the influence of the antiepileptic drugs carbamazepine (CBZ), phenytoin (PHT) and valproic acid (VPA) on different aspects of visual perception in patients with epilepsy by three different methods. (i) The colour arrangement test Farnsworth Munsell D100. (ii) A monitor system generating 24 different Gaussian dots and 24 different vertical sinusoidal gratings. Luminance increments and decrements for achromatic discrimination and four different colours for chromatic discrimination were investigated with four different sizes each adding up to 24 stimuli. (iii) A Maxwellian view system providing a foveal blue test light either superimposed on a yellow adaptation field (increment threshold) or after switching off this field (postadaptation threshold). Five different adaptation levels were investigated. Patients on PHT offered the most abnormalities, particularly in the D100 and in all Gaussian dots recordings. The individual differences between increment and postadaptation threshold (transient tritanopia effect) were significantly elevated at the four higher adaptation levels, whereas no change was found in the increment thresholds and only for the highest luminance level in the postadaptation thresholds. With VPA, chromatic and achromatic increment discrimination was impaired particularly for larger Gaussian stimuli on the monitor system. Valproic acid also induced a consistent increment threshold increase on the Maxwellian view system, an increase of the postadaptation threshold at the highest luminance level and, like PHT, an increase of the threshold differences at level 3 and 4, but not at the highest background level 5. Patients on CBZ provided normal results in all investigations, with the exception of a slight but significant increase in the D100 error score. Sinusoidal gratings turned out to be much less sensitive than Gaussian dots since they remained unchanged in patients on all three drug groups.

Adult↗
PubMed1996

Differential expression of versican isoforms in brain tumors.

Versican is a member of the family of large aggregating chondroitin sulfate proteoglycans which are one of the major constituents of brain extracellular matrix (ECM). We examined the expression of versican splice variants at mRNA and protein levels in normal human brain and in gliomas, medulloblastomas, schwannomas, neurofibromas, and meningiomas. RT-PCR revealed transcripts for V0 and V1 in all tissues. V2 mRNA was restricted to gliomas and normal brain, while V3 mRNA was detected in all tissues except for medulloblastomas. Immunohistochemistry using antibodies to the glycosaminoglycan (GAG)-alpha attachment domain of versican (present in V0 and V2) revealed decreased staining of most glioma ECMs compared to normal neuropil, while some abnormal tumor vessels, but not normal cerebral vessels, were GAG-alpha-positive. Expression of the GAG-beta attachment domain (present in V0 and V1) was faint in normal neuropil and cerebral vessels, but increased in tumor vessels and was absent in most glioma ECMs. Both GAG-alpha and GAG-beta were expressed in connective tissue of all nonglial tumors. Our data suggest that V2 is the major versican isoform of normal neuropil and glioma ECM. Furthermore, increased expression in tumor vessels and decreased expression in glioma ECM of the anti-adhesive versican may be related to marked local invasivity and rarity of extracranial metastasis of gliomas.

Base Sequence↗
PubMed1996

Serial transcranial Doppler monitoring after transient ischemic attack.

The natural course of ultrasonically detectable microembolism in patients with a symptomatic extracranial atherosclerotic lesion is not completely understood. Furthermore, the potential impact of therapeutic management on microemboli detection is anecdotal. A 58-year-old man who experienced a left-hemisphere transient ischemic attack presented with an extracranial ipsilateral high-grade carotid stenosis. He was studied 12 times in 12 months during different medical management, during which time he was symptom free, even though transcranial Doppler evidence of microemboli continued for 5 months.

Anticoagulants↗
PubMed1996

Self-contained, tetracycline-regulated retroviral vector system for gene delivery to mammalian cells.

Retroviral vectors that contain the tetracycline-inducible (Tet) system were developed. The two components of the Tet system were organized within the vectors in a manner that stringently maintains tetracycline-dependent regulation. Regulated expression of an indicator gene inserted into the retroviral vectors was examined in several different cell types. In infected NIH 3T3 cells, levels of induction in the absence of tetracycline were observed to be as much as 336-fold higher than levels in the presence of tetracycline, which were extremely low. Tetracycline-dependent regulation was observed in all other transduced cell types and ranged from 24- to 127-fold. The generation of retroviral vectors containing regulatory elements that allow for the regulated expression of heterologous genes and that have the ability to infect virtually all dividing target cells should greatly facilitate the biochemical and genetic examination of a broad range of genes. Moreover, these inducible retroviral vectors should prove useful in gene therapy applications.

3T3 Cells↗
PubMed1996

Diffuse brain invasion of glioma cells requires beta 1 integrins.

Diffuse invasion of brain tissue by single tumor cells is a characteristic feature of gliomas and a major reason why these tumors cannot be completely resected. The molecular basis of brain invasion is poorly understood. We regulated the expression of beta 1 integrins, the major group of extracellular matrix receptors, in astrocytic tumor cells by using a tetracycline-dependent transcription control system. Rat C6 glioma cells were stably transfected with (a) the tetracycline-controlled transactivator (tTA) gene, (b) antisense beta 1 cDNA under the control of a tTA/tetracycline-responsive promoter, and (c) the beta-galactosidase (lacZ) gene for histochemical identification. In one clone, C6TL beta, beta 1 protein levels were unaffected in the presence of tetracycline, but they were reduced by 60% in the absence of tetracycline because of production of antisense mRNA. C6TL beta cells were transplanted into the striatum of nude mice. After 14 days in the presence of tetracycline in the drinking water, tumors showed diffuse brain invasion, mainly along vascular basement membranes. In the absence of tetracycline, however, tumor cells were compact and generally well delineated from the surrounding brain tissue. These data, ie, blocking of brain invasion by antisense beta 1 mRNA, either because of disturbed interaction of beta 1 with brain extracellular matrix components or interference with beta 1-dependent signaling pathways, strongly suggest that beta 1 integrins are required for diffuse brain invasion of gliomas.

Animals↗
PubMed1995

Frontal and parietal premovement slow brain potentials in Parkinson's disease and aging.

During the anticipation of a stimulus that induces a predetermined pattern of behavior, a slowly increasing negative electric potential can be recorded from the human scalp at central and parietal electrodes and has been named contingent negative variation (CNV). We used a simple and a choice reaction time paradigm to investigate premovement potentials in patients with Parkinson's disease (PD) and in normal controls. There was a clear CNV in young subjects whereas it was negligible in the elderly control subjects and absent in the patients. In addition, we found a slowly increasing positive frontal potential. In normals the steepness of this potential decreased with the complexity of the task (simple vs. choice) and with age. This difference was abolished in the patients: If a slowly increasing positivity was observed at all, it was, on average, larger in the choice task. Reaction times of the patients were disproportionally prolonged in the simple compared to the complex task. These findings support the hypothesis that storing or initiating a simple preprogrammed motor response is more impaired in PD than selecting and initiating a motor response of a more complex task. The electrophysiological recordings suggest that impaired activation of the frontal lobes may be responsible for this deficit.

Age Factors↗
PubMed1995

Expression of type VII collagen, the major anchoring fibril component, in normal and neoplastic human nervous system.

The distribution of type VII collagen was examined in the normal human nervous system, in brain tumour biopsies and in glioma cell lines by immunohistochemistry and western blotting. In normal tissue, positivity was observed beneath choroid plexus epithelial cells and around pineal gland and pituitary gland cell nests, while other brain regions and peripheral nerves were negative. Expression was preserved in most related tumours (choroid plexus papilloma, pineoblastoma, pituitary adenoma). Scattered abnormal vessels showed neo-expression of type VII collagen in about half of the astrocytic and ependymal tumours. Glioma cells in situ were consistently negative for type VII collagen, whereas the glioblastoma cell lines were positive. Our results suggest that anchoring fibrils or at least epitopes of their major structural component are present in normal and pathological cerebral structures, indicating a unique distribution of type VII collagen in the nervous system.

Adult↗
PubMed1995

Mitochondrial dysfunction in adult-onset myopathies with structural abnormalities.

Three patients with chronic progressive external ophthalmoplegia of adult-onset, generalized muscle atrophy and myalgia are described. Two patients fulfilled the histological criteria for centronuclear myopathy, the third those for fiber-type disproportion. Additionally, typical ragged red fibers were found in all muscle specimens, and several muscle fibers were cytochrome c oxidase negative. NADH and succinate dehydrogenase stains showed increased subsarcolemmal accumulation of mitochondria. To determine whether these findings are coincidental or whether they indicated an additional mitochondrial disorder, all patients were investigated using biochemical analysis of the respiratory chain, molecular genetics, magnetic resonance spectroscopy of quadriceps muscle and ergometry. These tests suggested an additional mitochondrial dysfunction. Mitochondrial dysfunction seems to be more common in this group of myopathies than previously estimated, and may be of importance in the pathogenesis of these disorders.

Adult↗
PubMed1995

Primary central nervous system lymphomas--new pathological developments.

Primary central nervous system lymphomas (PCNSL) show increased incidence both in immunocompromised high-risk groups and in the general population. They are extranodal diffuse non-Hodgkin's lymphomas with a morphology similar to systemic lymphomas, but differ in their biological and molecular behaviour. The majority are large B-cell variants of high-grade malignancy; low-grade subtypes and T-cell lymphomas are rare; up to 50% remain unclassified according to the New Working Formulation and updated Kiel classification. Monoclonality of immunoglobulin receptor gene rearrangement can be diagnostically useful. The pathogenesis of PCNSL is obscure. Epstein-Barr virus (EBV) genome/proteins expression in two-thirds of HIV-related PCNSL but only in 15% of those in immunocompetent patients suggest different EBV latency stages in both types; human herpesvirus type 6 does not appear to play a pathogenic role. Comparison of expression patterns of integrin chains and adhesion molecules are very similar for PCNSL and nodal lymphomas suggesting that they are not selective mediators of lymphoma cell homing to the brain. In HIV-negative PCNSL they appear not to be influenced by EBV. Studies of protooncogenes (bcl-1 and bcl-2 genes) revealed no rearrangement in PCNSL, suggesting that they are not involved in the pathogenesis of PCNSL that probably do not differ cytogenetically from nodal B-cell lymphomas. Since most of the currently known molecular parameters are probably not the primary pathogenic events, the molecular genetics and pathogenesis of PCNSL are still to be elucidated.

Cell Adhesion Molecules↗
PubMed1995

Interactions of glioma cells and extracellular matrix.

The communication between tumor cells and extracellular matrix (ECM) is responsible for clinically important features of malignant gliomas, such as cerebral invasion and leptomeningeal spread. The synthesis of ECM components, ECM-degrading activities and ECM receptors as well as the interaction between ECM components and their receptors represents the molecular basis for these processes. Recent studies have shown that proteases and integrins, the major group of ECM receptors, may be over-expressed by astrocytic tumor cells. Furthermore, integrins and the hyaluronate receptor CD44 have been found to be involved in adhesion and basement membrane invasion of glioma cells. Critical issues which are poorly understood so far include the ECM composition of the normal human brain and of brain tumors, the function of individual ECM components and receptors in a neuro-oncological context, and the molecular processes mediating the diffuse invasion of glioma cells into the brain.

Animals↗
PubMed1995

Movement-related cortical potentials in persistent mirror movements.

Mirror movements (MMs) are involuntary movements executed on one side of the body during voluntary movements of the contralateral homologous body parts which may abnormally persist into adulthood. In 6 subjects affected by persistent MM with autosomal dominant inheritance, movement-related cortical potentials (MRCPs) during self-paced, voluntary extensions of either the left or right middle finger were recorded from 30 EEG electrodes simultaneously with the electromyogram (EMG) of both extensor digitorum communis muscles. The negative potentials before and during EMG onset were evaluated statistically for the two electrodes next to the cortical hand areas. A comparison with 7 normal subjects revealed no marked differences for the Bereitschaftspotential (BP) and the negative slope (NS'). Only in the periods around EMG onset (from -50 to +50 msec) a significant difference between both groups was found. The MM subjects showed fairly symmetric potentials over the right and left hemispheres, whereas the potentials of the control subjects were lateralized to the hemisphere contralateral to the intended movement. No difference was found for the amplitude of the maximum negative peak of MRCP following EMG onset. Our data showed no evidence for a different type of movement preparation in MM subjects as compared to normals. We propose that the additional ipsilateral cortical activation around movement onset may be the cortical mechanism, which compensates for abnormal ipsilateral corticospinal pathways in subjects with persistent MM.

Adolescent↗
PubMed1995

Embolus detection in different degrees of carotid disease.

Carotid atherosclerotic disease is a major source for artery to artery embolism. Stroke incidence highly depends on the degree of carotid stenosis. TCD monitoring for embolic signals may help to identify patients at high risk for an impeding stroke. This study was performed to correlate the degree of carotid stenosis with the occurrence of embolic signals and the clinical outcome. We performed a bilateral simultaneous TCD study on 4 patient groups with unilateral atherosclerotic disease: We studied patients with non-stenotic ICA plaques (n = 21), 50-75% ICA stenosis (n = 20), 75-95% stenosis (n = 22), and occlusion (n = 13). Minimum insonation time was 45 minutes. Embolic signals were not detected in the control group and patients with a non-stenotic ICA lesion, but in 10% of the patients with 50-75% stenosis, 22% of the patients with a high grade stenosis and 39% of the patients with an ICA occlusion. There is a high specificity (92%) and rather low sensitivity (29%) of these microemboli for past clinical events. The occurrence of embolic signals correlated (p < 0.005) with a history of stroke, TIA or RIND. Microemboli detection may be a valuable tool to identify high risk patients.

Adult↗
PubMed1995

Predominant affection of the blue cone pathway in Parkinson's disease.

Luminance contrast sensitivity and colour contrast thresholds were determined in 26 Parkinson patients and 17 normal controls of comparable age. They were psychophysically tested with a colour monitor system. Stimuli consisted of Gaussian enveloped luminance modulated or colour modulated (protan and tritan axis) vertical sine wave gratings with a spatial frequency of 1 cycle/degree. The stimuli subtended 4 degrees in diameter. Thresholds were determined using a two alternative forced choice method. Three different experimental conditions were explored: the detectability of stationary gratings, of moving gratings at velocities of 0, 2.5 and 5.0 cycles/s, and the detectability of horizontal square wave displacement at a frequency of 5 Hz for gratings of specified contrast levels. Intergroup differences were evaluated using two-tailed t tests with Satterthwaite corrections. Consistent and significant differences between normals and patients were found for tritan stimuli in the static and both dynamic conditions, and for luminance contrast stimuli in the displacement condition. Protan stimuli were much less apt to detect differences between the groups. We conclude that the retinal deficit of dopamine in Parkinson's disease is reflected in diminished centre/surround inhibition and that these changes are primarily apparent when vision is tested along the tritan axis, because blue cones are sparsely distributed.

Aged↗
PubMed1995

Inhibition of human motor cortex by ethanol. A transcranial magnetic stimulation study.

The non-invasive technique of focal transcranial magnetic stimulation (TMS) was used in six healthy volunteers to evaluate the effect of ethanol on four aspects of human central motor system excitability: (i) threshold intensity for the motor evoked potential (MEP) in the resting and active abductor digiti minimi muscle (ADM); (ii) variation of MEP amplitude with increasing stimulus intensity; (iii) duration of the TMS induced cortical silent period (CSP); (iv) intracortical inhibition and facilitation after paired magnetic stimulation. In addition, the maximum M wave (Mmax) after supra-maximal electrical ulnar nerve stimulation and the peripheral silent period (PSP) have been tested as parameters of peripheral motor excitability. Baseline measurements were compared with data obtained on a mean ethanol blood concentration of 0.8 ml/l. Resting and active motor thresholds remained unchanged. Also, the absolute Mmax values and the MEP/Mmax ratio at various TMS intensities were not affected by ethanol. The mean CSP duration was prolonged by up to 35 ms while the PSP duration showed no change. The principal effect of ethanol was an enhancement of intracortical inhibition and a suppression of intracortical facilitation. These results are discussed in relation to data from animal experiments which have shown a potentiation of gamma-aminobutyric acid (GABA) receptor-mediated currents as the main mode of action of ethanol in the mammalian cortex. It is suggested that CSP and intracortical inhibition reflect the activation of cortical GABAergic mechanisms by TMS, while motor threshold does not.

Adult↗