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Biomedical subjects

U Bogdahn

Publications and source records attributed to U Bogdahn.

At least 55 records · Page 3Linked to original sources
PubMed1995

Transforming growth factor-beta-mediated regulation of human peripheral blood mononuclear cell proliferation as detected with phosphorothioate antisense oligodeoxynucleotides.

Transforming growth factor-beta (TGF-beta) is a potent cytokine that has influence upon immunosuppressive as well as proinflammatory processes. In this context we have investigated the role of endogenous TGF-beta in human peripheral blood mononuclear cells (PBMCs) by TGF-beta 1 phosphorothioate antisense oligodeoxynucleotides (TGF-beta 1-S-ODNs). In short-term cultures (up to 3 days), TGF-beta 1-S-ODNs-treated, interleukin 2-activated PBMCs displayed a growth advantage (up to 148%) compared to nonsense or untreated controls as measured by cell counting and [3H]thymidine incorporation. Long-term antagonization of TGF-beta production (up to 12 days) showed no significant differences between both antisense- and nonsense-treated PBMCs. The efficacy and specificity of TGF-beta 1-S-ODNs effects was validated by gene expression studies (Northern blot and ELISA) and analysis of cellular uptake of BrdU-labeled S-ODN (Immunocytochemistry). TGF-beta 1-S-ODNs at the final concentration of 1 microM reduced TGF-beta 1 protein concentration up to 65% in PBMCs cultures without significant changes in TGF-beta 1 mRNA expression. These experiments demonstrate that TGF-beta 1-S-ODNs specifically antagonize TGF-beta 1-mediated autocrine suppression of IL-2-dependent PBMC activation. TGF-beta 1-specific antisense oligonucleotides may represent a promising immunoresponse modifying agent that could be used for T-cell directed immunostimulation.

Base Sequence↗
PubMed1995

Reduced echogenicity of brainstem raphe specific to unipolar depression: a transcranial color-coded real-time sonography study.

Echogenicity of the brainstem raphe was assessed in patients with major depression, bipolar affective disorders, and schizophrenia and compared with healthy adults employing transcranial color-coded real-time sonography. Forty probands were enrolled in each group. A highly significant reduction in raphe echogenicity was detected only in patients suffering from major depression. Echogenicity of the raphe was independent of age or sex and did not correlate with severity of the depressive syndrome or patient state. These findings are suggestive of structural desintegration of the brainstem raphe in unipolar depression, an anatomical region assumed to be a biological focus in the pathogenesis of depressive syndromes.

Adult↗
PubMed1995

1H NMR investigations of tumor spheroids grown from a human glioma biopsy or from a human malignant glioma cell line.

Three-dimensional spherical aggregates of cells, grown from a permanent human malignant glioma cell line (multicellular GaMG spheroids) and from a human glioma biopsy (fragment spheroids), were investigated by 1H NMR spectroscopy. In addition, 1H NMR spectra of biopsy specimens immediately after explantation and of cell monolayers from primary passage and passage 5 were acquired and compared to those of fragment spheroids. By allowing tumor cells to grow in a three-dimensional arrangement, many biological characteristics of the original tumor in vivo are preserved. A technical procedure was established, indicating that spheroids are particularly suited for NMR spectroscopic studies. Well-resolved proton NMR spectra were obtained from homogeneously reaggregated as well as from fragment spheroids which were immobilized in agar. We found that fragment spheroids closely resemble characteristic spectral patterns of the corresponding tumor tissue in vitro, thus making such tissue available for 1H NMR spectroscopic measurements under easy to standardize tissue-culture conditions. Furthermore, the effect of altering glucose supply on metabolism and growth was studied with multicellular GaMG spheroids. The spectroscopic differences found between cell suspensions and multicellular spheroids indicate that GaMG spheroids produce large amounts of lactate and that they can adapt their metabolism depending on glucose supply similar to tumors in vivo.

Biopsy↗
PubMed1995

Preoperative and postoperative follow-up in high-grade gliomas: comparison of transcranial color-coded real-time sonography and computed tomography findings.

Twenty patients with high-grade gliomas were prospectively studied by pre- and postoperative transcranial color-coded real-time sonography (TCCS) and CT, to determine the sensitivity of TCCS in the identification of residual tumor and tumor regrowth. Each patient was subjected to preoperative and early postoperative CT (postoperative day 1) and TCCS examinations (postoperative days 6 to 8) and subsequent CT and TCCS follow-up examinations within a time interval of 6 weeks to 3 months. In eight patients, a total of 15 biopsy specimens were intraoperatively obtained from the wall of the resection cavity. Histological findings of intraoperative biopsy specimens showed that hyperechogenic areas adjacent to the resection cavity always contained residual tumor tissue. Early postoperative TCCS identified these hyperechogenic areas in 19 of 20 patients. In 12 patients, postoperative CT revealed contrast enhancement at the resection margin, indicating residual tumor. In these patients the extension of these hyperechogenic areas on TCCS exceeded the contrast-enhancing areas on CT by a mean of 58%. In eight patients, postoperative CT displayed no contrast enhancement along the border of resection. TCCS and histological findings indicated residual tumor in seven of these eight patients. The size of the hyperechogenic lesions identified by postoperative TCCS increased in time and follow-up examinations revealed that tumor regrowth arose from these hyperechogenic areas in all patients. In four patients, tumor regrowth was identified, on average 0.7 months earlier by TCCS than by CT. From these data we conclude that the sensitivity of TCCS in detection of residual tumor and tumor regrowth seems to be superior to CT. The value of TCCS requires further clarification by comparative studies including histology and MRI.

Biopsy↗
PubMed1995

Transcranial color-coded real-time sonography of intracranial veins. Normal values of blood flow velocities and findings in superior sagittal sinus thrombosis.

Sonographic findings in patients with superior sagittal sinus thrombosis were compared to those in healthy adults. Two patients with angiographically verified superior sagittal sinus thrombosis were examined by transcranial color-coded real-time sonography (TCCS) after intravenous application of a pulmonary stable ultrasound contrast agent. For comparison, 10 patients without venous pathology had contrast-enhanced TCCS; in addition, 30 healthy adults had plain TCCS to determine the identification rate for deep and superficial venous segments and to define normal values of venous blood flow velocities. The straight sinus was identified in 22 of 30 healthy subjects by plain TCCS, and in 9 of 10 patients by contrast-enhanced TCCS. The mean peak and angle-corrected blood flow velocity was 19.1 +/- 7.1 cm/sec. The superior and inferior sagittal sinuses were identified by contrast-enhanced TCCS in 2 and 1 subjects, respectively; they were never seen on plain TCCS. In the 2 patients with sagittal sinus thrombosis a distinct increase of blood flow velocity was recorded from the straight sinus (83 and 92 cm/sec), most likely reflecting collateral circulation. These preliminary data indicate that TCCS and particularly contrast-enhanced TCCS permit identification and blood flow measurements within the deep and occasionally, the superficial venous system. TCCS may contribute to an assessment of hemodynamic repercussions of venous thrombosis and may indicate the risk of venous infarction and hemorrhage.

Adult↗
PubMed1995

Degeneration of substantia nigra in chronic Parkinson's disease visualized by transcranial color-coded real-time sonography.

To detect morphologic abnormalities in Parkinson's disease (PD), we examined 30 patients with PD and 30 age- and sex-matched nonparkinsonian controls by transcranial color-coded real-time sonography (TCCS). In 12 severely affected PD patients, the echogenicity of the substantia nigra was distinctly increased. In the remaining 18 PD patients and in all controls, the substantia nigra was poorly visualized or nondetectable by TCCS. The degree of hyperechogenicity of the substantia nigra closely correlated with the severity and duration of PD (p < 0.001). The increased echogenicity of the substantia nigra notably results from nigral gliosis and reflects the stage of degeneration.

Aged↗
PubMed1995

[The status of transcranial color-coded real time ultrasound in diagnosis of cerebral lesions].

Transcranial color-coded real-time sonography (TCCS) combines transcranial Doppler sonography and color-coded B-mode scanning of the brain parenchyma and cerebral vessels. This technique is not invasive and a broad spectrum of intracerebral lesions such as vascular lesions (ischemic stroke and intracerebral hemorrhage, aneurysms, arteriovenous malformations, arteriosclerotic vascular degeneration) and parenchymal lesions (brain tumors, degenerative and neuropsychiatric disorders) can be disclosed. Compared with MRI and CT, the ultrasound system is movable. Thus, it can be used easily in emergency rooms and intensive care units. In addition, TCCS can disclose new insights into the pathophysiology of disorders of the CNS, as in neuropsychiatric diseases. Ultrasound contrast agents improve the depiction of intracranial vessels. The pathology of the venous system can be identified.

Adult↗
PubMed1994

Cloning of a novel malignant melanoma-derived growth-regulatory protein, MIA.

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.

Amino Acid Sequence↗
PubMed1994

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

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.

Adolescent↗
PubMed1994

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

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.

Astrocytoma↗
PubMed1994

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

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.

Animals↗
PubMed1994

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

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 lesions 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 specimens. 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.

Biopsy↗
PubMed1994

Echogenicity of the brainstem raphe in patients with major depression.

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 sex-matched 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.

Adult↗
PubMed1994

Surgical intervention and heparin-anticoagulation improve prognosis of rhinogenic/otogenic and posttraumatic meningitis.

It is still controversial, whether early surgical removal of infectious material and heparin-anticoagulation to reduce vascular complications will improve outcome in acute meningitis. In the present pilot-study 40 patients with acute or delayed post-traumatic or oto-/rhinogenic purulent bacterial meningitis were analysed for neurological outcome by using the Glasgow outcome score (GOS) and the Tuthill functional score; patients were treated either by early surgical revision of the septic focus (Group 1, within 6 days, n = 15), late surgery (Group 2, later than 6 days, n = 19), or no surgery at all (Group 3, n = 6). All patients, independent of surgical approach, received therapeutic heparin-anticoagulation. Patient groups were otherwise comparable for antibiotic treatment, osmotherapy, microbiology, CSF-findings, CT-scans and prognostic factors. Outcome according to GOS was superior in Group 1 compared with Groups 2/3 (non-significant). Although there was no significant difference on admission in the Tuthill functional score, Group 1 achieved a superior final outcome of 96 points compared with Groups 2 and 3, who gained 72 points (p < 0.01). In addition, Group 1 patients had significantly less intracranial complications (8/15 patients versus 21/25 patients in Groups 2/3, p < 0.01) and were dependent upon respirator treatment for fewer days (10.2 days) than Groups 2/3 (12.5 days, non-significant). In 31 patients CSF-leakage was identified: among these, 17 patients had CSF-leakage, which had not been anticipated by clinical/neuroradiological examinations and revealed only by surgery. The overall mortality in this study population was very low (2.5%), therefore, therapeutic heparin seems to represent an additional favorable treatment measure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

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

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.

Adult↗
PubMed1994

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

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 shift and signal intensities; these atypical flow patterns were also detected in some low-grade tumors. CONCLUSION: In addition to depiction of primary CNS tumors in B-mode, contrast-enhanced TCCS enables evaluation of vascularization associated with tumor parenchyma.

Adult↗
PubMed1994

Doppler enhancement with SH U 508A in multiple vascular regions.

PURPOSE: To determine the magnitude and duration of peripheral vascular and cardiac Doppler signal enhancement after intravenous administration of contrast agent SH U 508A. MATERIALS AND METHODS: Suboptimal cardiac or peripheral vascular Doppler examinations were evaluated. A total of 75 intravenous bolus injections were made in 30 patients. Spectral audio Doppler intensity was measured throughout the duration of contrast effect. RESULTS: No clinically relevant adverse effects were noted, and Doppler enhancement was apparent in all cases. The diagnostic confidence of the investigators when scored before and after Doppler enhancement improved from 35% to 91% (P < .05). Doppler intensity increased more than 16 dB in all vascular regions investigated (P < .05). The contrast effect lasted for more than 120 seconds in the peripheral vascular and cardiac groups at equivalent doses. CONCLUSION: Intravenously administered SH U 508A is effective in markedly increasing cardiac, femoral arterial, and transcranial (cerebral arterial) Doppler signal intensity. The effect improves the clinical diagnostic confidence in cases of suboptimal unenhanced Doppler examinations.

Cerebral Arterial Diseases↗