Showing papers by "Ulrich Bogdahn published in 1994"

Cloning of a Novel Malignant Melanoma-derived Growth-Regulatory Protein, MIA

Abstract: Growth and progression of malignant melanoma cells is influenced by a complex network of growth-stimulating and -inhibiting factors produced by both the tumor cells and the local environment. Here we report the purification and molecular cloning of a novel growth regulating protein, designated melanoma inhibitory activity (MIA) and provide a preliminary functional characterization. MIA is translated as a 131-amino acid precursor and processed into a mature 107-amino acid protein after cleavage of a putative secretion signal. A murine complementary DNA was isolated that encoded a MIA-protein with 88% amino acid identity. MIA is secreted into the culture supernatant by several malignant melanoma cell lines as an M(r) 11,000 autocrine growth factor and acts as a potent tumor cell growth inhibitor for malignant melanoma cells and some other neuroectodermal tumors, including gliomas. MIA has no homology to any other known protein and, therefore, represents a novel type of growth-regulatory factor. Furthermore, we describe a molecular approach to express functionally active MIA in Escherichia coli, which might be attractive as a future antitumor therapeutical substance.

Echogenicity of the brainstem raphe in patients with major depression

Abstract: A novel transcranial ultrasound technique was used to detect differences in the echogenicity and echotexture of the brainstem dorsal raphe nucleus in 20 patients with major depression compared with 20 age- and sexmatched healthy adults. Transcranial color-coded real-time sonography visualized the mesencephalic and pontine brainstem and its midline structure. The echogenicity of the raphe was classified in a four-point scale. Compared with healthy subjects, the depressed patients were characterized by a significant decrease in the echogenicity of the brainstem raphe. The echogenicity score was not correlated, however, with measures of psychopathology such as the Hamilton Rating Scale for Depression, the Clinical Global Impression Scale, the Global Assessment Scale, or the Depression Scale of von Zerssen. These preliminary findings suggest that the brainstem raphe may be involved in the etiopathogenesis of major depression. The echogenicity score should be further evaluated as a possible trait marker in different types of affective disorders.

Identification of ventricular enlargement and estimation of intracranial pressure by transcranial color-coded real-time sonography

Abstract: Transcranial color-coded real-time sonography (TCCS) was applied to 26 patients with ventricular enlargement to quantify the ventricular size and to estimate intracranial pressure. Intracranial pressures, as determined by lumbar, epidural, or ventricular tonometry, ranged from 6.5 to 55 cm H2O (8 patients had pressures > 18 cm H2O). The widths of the third ventricle and the frontal horns of both lateral ventricles depicted by TCCS were compared to corresponding computed tomography data: TCCS and computed tomography findings correlated well for the third ventricle (r = 0.96) and for the right (r = 0.86) and left (r = 0.92) frontal horns. The capability of the septum pellucidum to undulate relative to the ventricular wall during short (20-degree) rotatory movements of the head was related to intracranial pressure. In all patients with intracranial pressure below 17 cm H2O, rotatory head movements induced septum pellucidum undulation; no lateral deflection of the septum pellucidum was found in patients with an intracranial pressure above 21 cm H2O. Therefore, TCCS may be employed to quantify and follow-up ventricular enlargement. Dynamic neurosonographic tests may allow a gross estimation of intracranial pressure.

ANTISENSE-OLIGONUCLEOTIDES FOR THE TREATMENT OF IMMUNOSUPPRESSIVE EFFECTS OF TRANSFORMING GROWTH FACTOR-β (TGF-β)

Abstract: Antisense-oligonucleotides or effective derivatives thereof hybridizing with an area of a gene coding for transforming growth factor-β (TGF-β) comprising the following nucleic acid sequences identified in the sequence listing under SEQ ID No. 1 - 56 and 137 or comprising the following nucleic acid sequences identified in the sequence listing under SEQ ID No. 57 to 136 each of the nucleic acids having a DNA- or RNA-type structure.

Vascularization of primary central nervous system tumors: detection with contrast-enhanced transcranial color-coded real-time sonography.

Abstract: PURPOSE: To study the potential of contrast material-enhanced transcranial color-coded real-time sonography (TCCS) in detection of primary intracranial tumor vascularization. MATERIALS AND METHODS: Primary central nervous system (CNS) tumors in 28 patients were examined with TCCS before and during administration of a transpulmonary, stable, galactose, microparticle-based ultrasound (US) contrast agent. All patients underwent cranial computed tomography and magnetic resonance imaging; nine patients also underwent intraarterial digital subtraction angiography. RESULTS: All lesions were hyperechoic on B-mode US scans except one grade 2 astrocytoma. The location and extent of hyperechoic lesions correlated well with findings on CT scans and MR images. After injection of contrast material, color Doppler flow signals were seen in nine of 14 low-grade lesions and 14 of 14 high-grade lesions. High-grade malignant tumors always had atypical arterial and venous Doppler spectra with irregular distribution of Doppler...

Reliability of transcranial colour-coded real-time sonography in assessment of brain tumours: correlation of ultrasound, computed tomography and biopsy findings

Abstract: Transcranial colour-coded real-time sonography (TCCS) was carried out in 25 patients with brain tumours to determine whether this noninvasive method provides additional information about the extent of solid tumour, its differentiation from oedema, and its tissue components. All 25 patients had serial computed tomography (CT)-guided stereotactic biopsies. Comparison of ultrasound, CT and histological findings revealed that the vast majority of contrast enhancing areas on CT were hyperechogenic (32/33; 97%) and contained tumour tissue (29/32; 91%). Hyperechogenic areas always represented solid tumour (23/23 patients), even when CT showed low density non-enhancing lesions. In lestons hypoechogenic on TCCS and low density on CT, histology consistently revealed necrotic tumour (7/7). Biopsies obtained from parenchyma with normal echogenicity revealed tumour in only 3 of 16 speciemens. Despite the high specificity of TCCS in the differentiation of tumour components, its sensitivity to tumour was inferior to that of CT (24/25; 96%). TCCS thus allows noninvasive preoperative identification of tumour tissue and its extent setting.

High-resolution one- and two-dimensional 1H MRS of human brain tumor and normal glial cells

Abstract: Astrocytoma (WHO grade II, III), glioblastoma, malignant melanoma, and normal glial cell cultures, established from biopsies, were investigated by 1H MRS. At a 1H resonance frequency of 500 MHz (11.75 T) a high spectral resolution was achieved in 1D 1H spectra; in conjunction with 2D shift-correlated (COSY) MRS, resonances of alanine, aspartate, choline, creatine, glutamate, glutamine, hypotaurine, myo-inositol, phosphocreatine, phosphoryl-ethanolamine, phosphoryl-choline, lactate, lysine, N-acetylaspartate, taurine, threonine and valine could be identified. T1 relaxation times for the most prominent compounds are presented. T1 values of lactate ranged between 450 ms and 850 ms. The intensity of the lactate signal revealed differences between individual spectra, but exhibited no correlation between different tumor specimens or degree of malignancy. It was shown that the lactate signal at 1.3 ppm is covered by peaks arising from threonine and fatty acids. The choline signal level varied among spectra of different tumors, among tumors with similar degree of malignancy, and within the same tumor. Further preliminary differences due to aspartate, inositol and glutamine/glutamate were found in 1D and 2D COSY spectra between normal glial cells as well as different tumors. These results indicate that some differences observed in in vivo spectra may be attributable to secondary macroscopic structural changes (hypoxia, necrosis) and not to tumor inherent characteristics. Further correlation between in vivo and in vitro spectroscopy is therefore required.

Melanoma-inhibiting protein

Abstract: A melanoma-inhibiting protein, nucleic acid sequences that code for said protein, a process for preparing said protein and its use for preparing a therapeutic agent are disclosed.

Antisense-oligonucleotides for the treatment of immuno-suppressive effects of transforming growth factor-b2(TGF-b2)

Abstract: Antisense-oligonucleotides or effective derivatives thereof hybridizing with an area of a gene coding for transforming growth factor-β (TGF-β) comprising the following nucleic acid sequences identified in the sequence listing under SEQ ID NO. 1-56 and 137 or comprising the following nucleic acid sequences identified in the sequence listing under SEQ ID NO. 57 to 136 each of the nucleic acids having a DNA- or RNA-type structure.

Investigation of the 1H NMR visibility of lactate in different rat and human brain cells.

Abstract: In recent years, 1H MRS has been used in a number of studies to measure the lactate content of brain, and it is generally assumed that the methyl resonance at 1.3 ppm reflects the total amount of lactate present in the tissue. However, reduced NMR visibility of lactate has recently been reported for blood, heart and skeletal muscle as well as for bacteria. We have assessed the NMR visibility of lactate in cultures of human and rat brain cells, comparing the concentrations measured by NMR and by biochemical methods. Contributions of fatty acids have been eliminated using their different relaxation behavior. We found approximately 30% of the lactate to be undetectable by NMR in the studied cell cultures. While the mechanism partially masking lactate in 1H spectra is not yet understood, the potential invisibility of some pools of lactate to NMR may greatly affect the interpretation of brain spectra.

In vitro studies of cytokine-mediated interactions between malignant glioma and autologous peripheral blood mononuclear cells

Abstract: The humoral interactions between three malignant glioma early-passage cell cultures and in vitro interleukin (IL)-1 alpha- and IL-2-activated autologous peripheral blood mononuclear cells (PBMC's) were investigated, employing standard and modified (separated by permeable membranes) mixed lymphocyte tumor cell (MLTC) cultures. In modified MLTC's, glioma cells clearly inhibit proliferation of PBMC's (up to 60%), whereas lymphokine-activated PBMC's enhance glioma cell growth up to 12-fold, as determined by 3H-thymidine incorporation assays. Glioma cells produce both stimulatory (IL-6) and inhibitory proteins (transforming growth factor-beta) for PBMC's. Lymphokine-activated PBMC's secrete IL-1 alpha, IL-2, IL-4, IL-6, interferon-gamma, and tumor necrosis factor-alpha, which may modulate glioma cell proliferation. None of these cytokines stimulated glioma cells as intensely as modified MLTC systems. These observations indicate that in vitro lymphokine-activated PBMC's, although suppressed by humoral glioma-derived factors, may enhance glioma cell proliferation with soluble factors secreted into the culture medium. The authors conclude that glioma-lymphocyte growth regulatory networks include stimulatory and inhibitory factors from both cell populations, which may modulate tumor progression. These observations may have relevance for adoptive immunotherapy in patients with gliomas.

Contribution of transcranial color‐coded real‐time sonography to the etiopathogenetic classification of middle cerebral artery stenosis

Abstract: Transcranial color-coded real-time sonography (TCCS) and cranial computed tomography were applied to patients with middle cerebral artery (MCA) stenosis to evaluate whether these techniques may disclose additional aspects of the pathophysiology of the stenotic lesion. In 15 patients with MCA stenosis identified by transcranial Doppler sonography, the echogenicity of the stenotic segment was estimated subjectively by TCCS. The density of the stenotic segment, prior to being detected by TCCS, was quantified by computed tomography. In 5 of the 15 patients, transcranial image-directed Doppler sonography identified a hyperechogenic lesion in association with the stenotic vascular segment; computed tomography demonstrated a “dense” artery (Hounsfield units [HU] > 120) in the corresponding vascular segment. In 10 patients the echogenicity of the stenotic segment was found to be normal, with a computed tomography density of >100 HU in the corresponding segment. Hyperechogenic and hyperdense stenotic vascular segments in TCCS and computed tomography, respectively, may indicate an arteriosclerotic vascular lesion with calcium deposits. Normal echogenicity and normal to slightly elevated computed tomography-density of a stenotic vascular segment may suggest the presence of a thrombotic/embolic lesion. © 1994 John Wiley & Sons, Inc.

Deuterium enthaltende pharmazeutische Zusammensetzung als Zytostatikum oder Tumor-Therapeutikum

Abstract: The invention pertains to the use of a pharmaceutical composition containing deuterium and/or deuterated substances and/or substances that enrich or release deuterium to selectively destroy tumor cells and/or tumor metastases or to prevent metastasizing and/or local recurrence of tumors as well as their regrowth.

Antisense-oligonucleotides for transforming growth factor-β (TGF-β)

Abstract: Antisense-oligonucleotides or effective derivatives thereof hybridizing with an area of a gene coding for transforming growth factor-β (TGF-β) comprising the following nucleic acid sequences identified in the sequence listing under SEQ ID NO. 1-56 and 137 or comprising the following nucleic acid sequences identified in the sequence listing under SEQ ID NO. 57 to 136 each of the nucleic acids having a DNA- or RNA-type structure.

Pre- and Intraoperative Transcranial Color-Coded Real-Time Sonography in Stereotactic Biospies of Midline Tumors

Abstract: Diffusely infiltrating tumors of midline structures (corpus callosum, basal ganglia, brainstem) are regarded to be difficult for surgical planning mainly because of poor differentiation between solid tumor tissue and peritumoral edema by computed tomography (CT) and magnetic resonance imaging (MRI). Encouraged by the positive results of transcranial color-coded real-time sonography (TCCS) in brain tumor localization [1, 2], we applied this technique to stereotactic biopsies pre- and intraoperatively to investigate its potential in preoperative planning and intraoperative real-time imaging monitoring.

DNA fragments activated in expression of melanoma inhibiting protein (MIA)

Abstract: Expressionsaktivierende Nukleinsaurefragmente aus dem 5'-untranslatierten Bereich von SEQ ID NO:3 sind zur Herstellung von viralen oder nicht-viralen Vektoren fur die Gentherapie geeignet. Activating expression nucleic acid fragments from the 5 'untranslated region of SEQ ID NO: 3 are suitable for the preparation of viral or non-viral vectors for gene therapy.

OLIGONUCLEOTIDES ANTISENS DESTINES AU TRAITEMENT DES EFFETS IMMUNO-SUPPRESSEURS DU FACTEUR TRANSFORMANT DE CROISSANCE-$g(b) (TGF-$g(b))

Abstract: Oligonculeotides antisens ou derives efficaces de ceux-ci, hybridant avec une zone d'un gene codant pour le facteur transformant de croissance β (TGF-β) et comprenant les sequences d'acide nucleique identifiees dans la liste de sequences par les numeros d'identification 1 - 56 et 137, ou comprenant les sequences d'acide nucleique identifiees dans la liste de sequences par les numeros d'identification 57 a 136, chacun des acides nucleiques presentant une structure du type ADN ou ARN.

Proteine d'inhibition de melanomes

Abstract: L'invention concerne une proteine d'inhibition de melanomes, des sequences d'acides nucleiques de codage de ladite proteine, un procede de preparation de cette proteine et son utilisation pour preparer un agent therapeutique.

Melanom-inhibierendes protein

Abstract: Die Erfindung betrifft ein Melanom-inhibierendes Protein, fur dieses Protein codierende Nukleinsauresequenzen, Verfahren zur Gewinnung dieses Proteins sowie dessen Verwendung zur Herstellung eines Therapeutikums.