Search PubMed⌕ Search

Biomedical subjects

W Paulus

Publications and source records attributed to W Paulus.

At least 199 records · Page 11Linked to original sources
PubMed1995

Effects of transforming growth factor-beta 1 on collagen synthesis, integrin expression, adhesion and invasion of glioma cells.

Transforming growth factor-beta 1 (TGF-beta 1) as a potent modulator of cell-extracellular matrix (ECM) interactions may be related to poorly understood ECM-associated features of glioblastomas, such as diffuse brain invasion, rarity of extracranial metastasis and marked ECM production in vitro. We therefore studied TGF-beta 1 expression in glioblastoma biopsy specimens and cell lines by using reverse transcription-polymerase chain reaction (RT-PCR). The cell lines were also examined by Western blotting and immunocytochemistry. To determine effects of TGF-beta 1, glioma cell lines U-138MG and U-373MG were incubated for 48 hours with TGF-beta 1 (0.1, 1, 10 ng/ml) or with antisense phosphorothioate-oligodeoxynucleotides (APO) designed to specifically inhibit TGF-beta 1 gene expression. Thereafter, collagen synthesis was determined by isotopic labeling with 3H-proline; integrin expression by flow cytometry; adhesion on collagen types I and IV, laminin and fibronectin by adhesion assays; and invasion through reconstituted basement membrane by invasion assays. We found that TGF-beta 1 was expressed by all glioma cell lines at protein and mRNA levels. Pretreatment with TGF-beta 1 increased the amount of collagen synthesis/cell, upregulated the alpha 5 integrin chain of U-138MG cells, and facilitated adhesion on all ECM substrates, while invasion of U-138MG cells, but not that of U-373MG cells, was markedly reduced. Conversely, pretreatment with APO reduced TGF-beta 1 protein expression levels, inhibited adhesion and increased invasion of U-138MG cells, but did not affect collagen synthesis. We conclude that exogenously applied TGF-beta 1 exerts marked effects on ECM-related features of glioma cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1995

Gene therapy for brain tumors.

Gene therapy has opened new doors for treatment of neoplastic diseases. This new approach seems very attractive, especially for glioblastomas, since treatment of these brain tumors has failed using conventional therapy regimens. Many different modes of gene therapy for brain tumors have been tested in culture and in vivo. Many of these approaches are based on previously established anti-neoplastic principles, like prodrug activating enzymes, inhibition of tumor neovascularization, and enhancement of the normally weak anti-tumor immune response. Delivery of genes to tumor cells has been mediated by a number of viral and synthetic vectors. The most widely used paradigm is based on the activation of ganciclovir to a cytotoxic compound by a viral enzyme, thymidine kinase, which is expressed by tumor cells, after the gene has been introduced by a retroviral vector. This paradigm has proven to be a potent therapy with minimal side effects in several rodent brain tumor models, and has proceeded to phase 1 clinical trials. In this review, current gene therapy strategies and vector systems for treatment of brain tumors will be described and discussed in light of further developments needed to make this new treatment modality clinically efficacious.

Antibody Formation↗
PubMed1995

High-resolution activation mapping of basal ganglia with functional magnetic resonance imaging.

We investigated the activation of the putamen and the external and internal division of the globus pallidus in 12 normal volunteers during rapid supination and pronation of their right or left hand, using functional MRI (fMRI). We observed an increase in signal intensity varying from 3.1 +/- 1.2% to 23.4 +/- 2.3% during activation. Activated areas were predominantly contralateral to the moving hand and smaller than 5 mm2. These findings indicate that fMRI allows study of the normal function of basal ganglia and may be of value in the investigation of basal ganglia disorders.

Adult↗
PubMed1995

NF2 gene analysis distinguishes hemangiopericytoma from meningioma.

The histogenesis of dural-based or "central" hemangiopericytomas (cHPCs) remains controversial. Some authors consider these tumors variants of meningiomas while others consider them akin to peripheral hemangiopericytomas (pHPCs). Meningiomas frequently have mutations in the neurofibromatosis 2 (NF2) gene, providing a molecular marker for meningiomas and other NF2-related tumors. We therefore analyzed the NF2 gene in cHPCs, pHPCs, and meningiomas to determine whether cHPCs are more similar at the molecular genetic level to meningiomas or pHPCs. Using paraffin-embedded archival material from 28 cHPCs (including three primary and recurrent tumors), 10 pHPCs, and 26 meningiomas, we scanned all 17 exons of the NF2 gene and flanking intronic sequences for mutations with single strand conformation polymorphism analysis and DNA sequencing. No NF2 mutations were found in either cHPCs or pHPCs, whereas 35% of meningiomas had NF2 gene alterations (P < 0.001). The NF2 gene mutations in meningiomas were all truncating mutations, consistent with previous studies. Our findings suggest that cHPCs are distinct from meningiomas at the molecular genetic level and support prior clinico-pathological data that distinguish these tumor-entities.

Adult↗
PubMed1995

Postural stability differentiates "lower body" from idiopathic parkinsonism.

INTRODUCTION: Patients with an akinetic Parkinson syndrome of the lower extremities and a poor response to L-DOPA have been described as "lower body Parkinsonism" (LBP). These patients are characterized by frequent fallings and poor balance. METHODS: We have studied body sway with static (force platform) and dynamic (Equitest) posturography in 11 LBP patients, 6 of them revealing deep white matter lesions on MRI and 10 patients with advanced Parkinson's disease (PD) and compared performance with 30 age-matched controls. RESULTS: When standing on a fixed support the postural performance of both patient groups lay within the normal range. The balance of LBP patients worsened in the static testing in the conditions "eyes open on foam" (p < 0.05) and "eyes closed on foam" (p < 0.0006, of 11 patients falling), whereas the balance of PD patients deteriorated only with "eyes closed on foam" (p < 0.05). Dynamic posturography confirmed these results in 6 different sensory conditions, clearly distinguishing the more unstable LBP patients from PD patients during "standing, eyes closed, foot support sway referenced" (p < 0.005). CONCLUSION: We conclude, that postural adjustments in LBP patients are more disturbed than those in PD patients and posturography can be an additional tool for the differential diagnosis of Parkinson syndromes with gait disorders.

Aged↗
PubMed1995

Sclerosis of the skin in the GEMSS syndrome. An overproduction of normal collagen.

BACKGROUND: We describe a recently observed set of autosomal dominant GEMSS (glaucoma, lens ectopia, microspherophakia, stiffness of the joints, and shortness) syndrome in a 47-year-old woman and her 23-year-old son. In addition, sclerosis of the skin, from which both patients suffered, is investigated in detail. OBSERVATIONS: The histologic examination of skin biopsy specimens obtained from the upper aspects of the backs of both patients revealed a markedly thickened dermis. Immunohistochemical examination of the dermal collagen bundles showed a collagen pattern similar to systemic sclerosis and normal control skin. In situ hybridization showed a markedly enhanced gene expression of transforming growth factor beta 1. CONCLUSION: The sclerotic skin changes in GEMSS syndrome are the result of an abnormally increased production of normal collagen that might be attributable to the enhanced in situ production of transforming growth factor beta 1.

Abnormalities, Multiple↗
PubMed1995

[Disorders of color perception and increase glare sensitivity in phenytoin and carbamazepine therapy. Ocular side effects of anticonvulsants].

Advanced psychophysical tests, performed in 42 epileptic patients, show that the antiepileptic drugs phenytoin and carbamazepine can specifically affect the retinal function, while Valproic Acid and the epileptic seizures do not. The Farnsworth-Munsell 100-Hue and Panel D-15 désaturé tests revealed an accumulation of errors along the tritan/tetartan axis (blue colour vision deficiencies) and a high total error score. The same defect was shown by measurement of the spectral sensitivity functions. The results obtained for mesopic vision and especially glare sensitivity measured by nyktometry were markedly affected in these patients compared to a normal population. The enhanced sensitivity to glare is mainly the only one symptom complained by the patient. We propose a screening method for early detection of phenytoin- and carbamazepine-induced neurotoxicity. The literature of ocular side effects of anticonvulsant drugs is carefully reviewed.

Adolescent↗
PubMed1995

[Sensitive physiologic perceptual tests for ocular side effects of drugs exemplified by various anticonvulsants].

Advanced psychophysical tests, performed in 42 patients who have seizures, showed that the widely used antiepileptic drugs, diphenylhydantoin and carbamazepine, can specifically affect retinal function, while valproic acid and the epileptic seizures do not. The Farnsworth-Munsell 100-Hue and Panel D-15 désaturé tests revealed an accumulation of errors along the tritan/tetartan axis and a high total error score. As shown by measurement of the so-called transient tritanopia and by determination of the spectral sensitivity, this blue vision defect is not only due to loss of postreceptoral interaction between long- and short-wavelength-sensitive cones, but is also based on a disturbance in the receptor mechanism itself. The dark adaptation curve was not affected. As determined by cone flicker thresholds during dark adaptation, the inhibitory action of rods on cones is reduced. The results obtained for mesopic vision and especially glare sensitivity measured by nyktometry were markedly affected in these patients compared to the normal population. The psychophysical methods provide a very sensitive test for early detection of drug-induced retinal dysfunction and allow clear differentiation between the loss of a receptor mechanism and a defect in the neuronal interaction between photoreceptors in the human visual system induced by antiepileptics.

Adolescent↗
PubMed1995

Messenger RNA expression of the immunosuppressive cytokine IL-10 in human gliomas.

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. Because patients with malignant gliomas present with a general impairment of the immune system, we investigated IL-10 expression in the glioma tissue. Because expression of IL-10 and IL-6 is associated in hematopoietic cells and IL-6 can act as an autocrine growth stimulator for glioblastoma cell lines, we looked in addition for a relationship between IL-10 and IL-6 expression. Using a quantitative reverse transcriptase polymerase chain reaction, IL-10 and IL-6 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 with low grade tumors, whereas 2 of 3 cell lines showed only weak constitutive expression, mRNA for IL-6 was found in 86.5% of all gliomas with a correlation concerning the expression levels for both cytokines in 69% of gliomas. We suggest that IL-10 may contribute to the progression of astrocytomas by suppressing the patient's immune response, whereas IL-6 provides an additional growth advantage.

Base Sequence↗
PubMed1994

Collagens, integrins and the mesenchymal drift in glioblastomas: a comparison of biopsy specimens, spheroid and early monolayer cultures.

To analyze the process of mesenchymal differentiation in vitro, we examined 5 human glioblastomas as biopsy specimens, monolayer cultures and 3-dimensional fragment spheroid cultures for the immunohistochemical expression of extracellular matrix (ECM) components (collagen types I, III-VI, laminin) and integrin receptors (beta 1, beta 2, beta 3 and beta 4 chains). mRNA for type-I and type-IV collagen alpha I chains was quantified using reverse transcription-polymerase chain reaction. In situ, glioma cells expressed beta 1, the common beta chain of most integrin ECM receptors, while ECM components were restricted to vascular elements. Early monolayer cultures showed a marked increase in ECM components (interstitial collagens more than basement membrane components), and coexpression of ECM components and glial fibrillary acidic protein (GFAP) by most cells. beta 2 and beta 3 integrins were upregulated in the primary cultures. In the fifth passages, GFAP-positive cells were decreased and collagen-expressing cells increased. The spheroids exhibited preserved GFAP staining, neoexpression of beta 4 integrin in some tumors, and variable ECM expression by glioma cells which was lower than that in monolayer cultures. ECM deposition usually commenced in central spheroid areas where the Ki-67 proliferation index was low. We conclude that different culture systems are characterized by distinct expression patterns for ECM components and receptors, and that mesenchymal features in cultured gliomas arise due to transdifferentiation of glioma cells.

Base Sequence↗
PubMed1994

Visual thresholds to low-contrast pattern displacement, color contrast, and luminance contrast stimuli in Parkinson's disease.

We used the computerized Moorfield Vision System to demonstrate specific increases in various perceptual visual thresholds in idiopathic Parkinson's syndrome. Fifteen patients were compared to 13 age-matched normals. Motion detection was impaired maximally (2 p < 0.01 and better in two-tailed t test) at luminance contrasts of 3-7%. Stimulus was an achromatic vertical 4 cycles/degrees sine wave grating subtending 3 degrees x 2 degrees, centered 5 degrees in the nasal field and oscillating at 5 Hz. In addition, stationary color and luminance contrast thresholds were tested with flashed display of 5 degrees x 6 degrees random letters, which were presented for 200 ms (color) and 50 ms (achromatic). Color discrimination was impaired in the tritan axis only (2 p < 0.05 in two-tailed t test). All achromatic stimuli--luminance increments, decrements, and phase reversing stimuli--were equally well seen by patients and controls. We conclude that the dopaminergic deficit of retinal amacrine cells in Parkinson patients can be monitored by combined low-contrast and motion (displacement) stimuli. Future studies will determine if moving colored targets are more effective in discriminating patients from controls than are the achromatic gratings used in this work.

Aged↗
PubMed1994

Dependence of visual stabilization of postural sway on the cortical magnification factor of restricted visual fields.

Monocular visual stabilization of fore-aft and lateral body sway was tested posturographically in normal subjects (wearing visual field blinds) as a function of visual field size and location of the visual field on the central or peripheral retina. Body sway applied to a force- measuring platform is less with central (foveal) vision when central and peripheral visual fields have the same area. If, however, the peripheral field size is corrected by the cortical magnification factor of the retina in the primary cortex, body sway is stabilized by the peripheral retina to the same extent. Thus, there is no functional specialization of central and peripheral retina with respect to balance control. Visual stabilization of upright stance is a function of field size and cortical representation of the retina. The central and the peripheral retina have different thresholds to detect motion; this was surprisingly not reflected in measurements of normal fore-aft and lateral body sway.

Adult↗
PubMed1994

Interphase cytogenetics of glioblastoma and gliosarcoma.

Interphase cytogenetics, i.e., in situ hybridization using probes to chromosome-specific DNA, enables histological identification of cells bearing numerical chromosome aberrations and cytogenetic analysis of composite tumors. We studied routinely processed tissues from seven glioblastomas and three gliosarcomas using biotinylated probes to pericentromeric alpha-satellite sequences on chromosomes 10, 17 and X. By applying various pretreatment protocols, an evaluable compromise between morphology and signal intensity was obtained in most cases. Compared to vascular cells with normal chromosomal counts, a significant subpopulation of glioblastoma cells showed monosomy 10 (four of five cases), monosomy 17 (one of seven cases) and loss of one X chromosome (one of seven cases). All monosomy 10 cases comprised additional areas where two copies of chromosome 10 were retained. Among the gliosarcomas, both the glioma and the sarcoma portion showed monosomy 10 in one case and monosomy 17 in another case. In contrast, in the third case of gliosarcoma, monosomy 10 was found only in the glioma portion, whereas a gain of chromosome X was observed in the sarcoma portion. We conclude that: (1) numerical chromosome aberrations can be detected in routinely processed brain tumor biopsy specimens using interphase cytogenetics, making retrospective studies feasible; (2) glioblastomas show intratumoral cytogenetic heterogeneity with formation of monoclonal cell clusters; and (3) sarcoma and glioma elements in gliosarcomas may exhibit the same or different numerical chromosome aberrations, suggesting various histogenetic pathways of the sarcoma-like portion.

Adult↗
PubMed1994

Large cell anaplastic (KI-1) brain lymphoma of T-cell genotype.

Three cerebral lesions were neuroradiologically detected in a 63-year-old man without evidence of an extracranial neoplasm. The biopsy specimen from one lesion showed a large cell anaplastic lymphoma (LCAL). Immunohistochemically, tumor cells were positive for CD3, CD30, CD45RO, and HLA-DR. The polymerase chain reaction (PCR) of the rearranged T-cell receptor beta chain genome (TcR beta) derived from paraffin sections showed monoclonality. This case shows that primary cerebral T-cell lymphomas genotypically correspond to nodal T-cell lymphomas, a correspondence that has previously been demonstrated for the more common brain lymphomas of B-cell lineage.

Brain Neoplasms↗
PubMed1994

Laparoscopic Myomectomy: Sonographic Follow-Up and Second-Look Laparoscopy for the Evaluation of a New Technique

Between 1988 and 1993, 100 women underwent laparoscopic myomectomy in the Department of Obstetrics and Gynecology of the University of Ulm. Indications varied, although most myomectomies were done for fertility enhancement or preservation. Closure of the incision, especially with an open uterine cavity, was done in two or three layers. Several technical limitations specific to laparoscopic surgery impair complete and satisfactory closure of the myomectomy incision. In this study we evaluate the new technique by sonographic control and second-look laparoscopy. In 22 cases second-look laparoscopy was undertaken to assess post-operative adhesion formation and to effect adhesiolysis. The rate of adhesion formation was 28%, depending on site, size, and number of myomas. Adhesion formation was significantly higher (p<0:005) in myomas located on the posterior wall. The density of adhesions did not vary significantly. In 22 cases sonography was done preoperatively, one day after the operation and 6 weeks postoperatively to compare wound healing, depending on myoma site and size. In 74% of cases an intramural hematoma of varying size was observed. By the third control, 6 weeks later, an irregular hypodense area was seen in only 8%. This study demonstrates that laparoscopic myomectomy entails the risks of postoperative adhesion formation and impaired wound healing, including intramural hematoma. So far no data are available showing a correlation between these risks and post-operative infertility or higher incidence of uterine rupture.

Journal Article↗