Biomedical subjects

U Bogdahn

Publications and source records attributed to U Bogdahn.

At least 73 records · Page 4Linked to original sources

PubMed1994

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

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.

Cells, Cultured↗

PubMed1994

Efficacy SH U 508 A (Levovist) as blood pool enhancer in the Doppler evaluation of multiple vascular regions.

SH U 508 A (Levovist) as a blood pool enhancer to investigate multiple vascular regions with Doppler ultrasonography. Thirty patients with sub-optimal cardiac or peripheral vascular Doppler exams received 75 intravenous contrast bolus injections in all to investigate the intensity and the duration of Doppler signal enhancement after the i.v. administration of an echo contrast agent - i.e., SH U 508 A (Levovist) by Schering AG, Berlin, Germany. All cases exhibited Doppler enhancement and the investigator's "diagnostic confidence" increased from 35% (precontrast) to 91% (post-contrast) (p < 0.05). Audio Doppler intensity was measured quantitatively and more than 16 dB enhancement was demonstrated in all the vascular regions under investigation (p < 0.05). Enhancement lasted more than 60 seconds in the peripheral vessels and 120 seconds in the heart vessels. No clinically relevant adverse reactions were ever observed. To conclude, i.v., -administered SH U 508 A (Levovist) is a valuable means of increasing cardiac, femoral arterial and transcranial (cerebral arterial) Doppler signal intensity. Enhancement is durable and improves the clinical diagnostic confidence in the patients with suboptimal Doppler findings.

Adult↗

PubMed1993

Autoinduction of platelet derived growth factor (PDGF) A-chain mRNA expression in a human malignant melanoma cell line and growth inhibitory effects of PDGF-A-chain mRNA-specific antisense molecules.

Autoinduction of PDGF-A-chain mRNA's was demonstrated in cells of a human malignant melanoma cell line (HTZ 19), indicating a PDGF-induced amplification of an autocrine growth factor loop mechanism. PDGF-alpha receptors were detected by immunocytochemistry in HTZ 19 melanoma cells. Exogenously administered PDGF-AA exerted an increase in cell proliferation by 70% at 200 ng/ml PDGF in serum-supplemented cell culture medium. Antisense phosphorothioate-oligodeoxynucleotides (S-ODN's), specifically targeted against PDGF-A-chain mRNA, reduced cell proliferation of HTZ 19 melanoma cells by 62% at a concentration of 5.0 microM, also only in serum-enriched medium. These findings strongly suggest that PDGF-AA homodimers may be an autocrine growth factor for HTZ 19 melanoma cells but require synergistic interaction with serum components.

Base Sequence↗

PubMed1993

In vitro studies on interaction of 4-hydroperoxyifosfamide and 2-mercaptoethanesulphonate in malignant gliomas.

Drug interference of ifosfamide and sodium 2-mercaptoethanesulphonate (MESNA) was studied in three malignant glioma cell cultures (HTZ-17, HTZ-209B, and HTZ-243) by a recently developed in vitro method for evaluation of multimodal treatment interactions. Glioma cell cultures were treated in monolayer 96-well tissue-culture plates for 2 h each, with 4-hydroperoxyifosfamide and MESNA combined in both sequences, or alone. Concentrations ranged from 0.01 microM to 50 microM in single-modality exposures, and from 0.01 microM to 10 microM in combination exposures. After five population doubling times, DNA synthesis was determined by a standard [3H]Tdr-incorporation liquid-scintillation-counting protocol. Data points were evaluated for mono- and combined treatment dose effects (adapted with a probit function), and a model-free three-dimensional response surface was created that was compared to the theoretical additive, anticipated response surface. Local additivity was analysed for any ratio of combined treatment. No tumour effects were seen with MESNA in single-drug exposure, whereas ifosfamide resulted in more than 90% inhibition of tumour DNA synthesis. In combination experiments, MESNA could be confirmed to be inert: the anticipated theoretical combination response surfaces formed a three-dimensional extension of the single-drug ifosfamide dose/response curves--the experimental combination response surfaces displayed an identical appearance (P < or = 0.05). In conclusion, these results indicate no drug interference of MESNA and ifosfamide in malignant glioma cells.

Antineoplastic Agents↗

PubMed1993

Differentiation between ischemic and hemorrhagic stroke by transcranial color-coded real-time sonography.

Transcranial color-coded real-time sonography was applied to 20 patients with ischemic stroke and 28 patients with spontaneous intracerebral hemorrhage. In all patients the sonographic diagnosis corresponded closely to cranial computed tomography findings. Recent hemorrhages were visualized as a hyperechodense mass. The high contrast to minor echodense adjacent parenchyma led to a clear sonographic distinction. Older clots were characterized by a continuous decrease of echodensity and subsequently were interspersed by hypoechodense zones. In the acute stage of ischemic infarction, the vessel occlusion (17/20) and collateral vascular supply (10/20) could be depicted in the color-B-mode in two perpendicular planes and further verified by the Doppler mode. Brain edema was not visualized. Although in the acute stage no change of echo texture was observed within the infarction, hyperechodense regions (7/11) could be observed in some patients during the time course. Complications of intracerebral hemorrhage and ischemic stroke, such as disturbance of cerebrospinal fluid circulation, midline shift, and compression of adjacent territories, were depicted by transcranial color-coded sonography. These preliminary results illustrate that transcranial color-coded real-time sonography may be helpful in the early noninvasive differential diagnosis as well as long-term follow-up in patients with cerebrovascular disorders.

Brain Ischemia↗

PubMed1993

Contrast-enhanced transcranial color-coded real-time sonography. Results of a phase-two study.

BACKGROUND AND PURPOSE: Transcranial color-coded real-time sonography has been developed as a promising new bedside procedure to monitor central nervous system parenchymal and vascular pathology; the present study was designed to investigate the potential role of galactose microparticles (SH U 508 A) as a new ultrasound contrast-enhancing agent for transcranial sonography. METHODS: Ten patients (four women and six men, 24-63 years of age) with a broad spectrum of central nervous system pathology were investigated by transcranial color-coded real-time sonography in a phase-two clinical study. After conventional ultrasound examination, all patients received a maximum of six injections of 10 ml with 200, 300, or 400 mg/mL SH U 508 A. The intracranial vessels were scanned by color flow imaging in the axial and coronal planes through a transtemporal acoustic bone window; in addition, the vertebrobasilar system was followed through the foramen magnum. RESULTS: SH U 508 A was well tolerated without side effects. In axial and coronal scans, the application of SH U 508 A resulted in detection of peripheral branches of the anterior, middle, and posterior cerebral arteries, as well as the posterior communicating and superior cerebellar arteries. In addition, the deep cerebral veins (i.e., inferior sagittal sinus, internal cerebral veins, great cerebral vein of Galen, straight sinus, and the confluence sinuum) were revealed. The transforaminal approach led to detection of the main infratentorial branches (anterior inferior, posterior inferior, and superior cerebellar arteries). One patient could not be insonated without contrast, but after SH U 508 A the trunks of the large intracranial arteries were detected. No obvious changes in the ultrasound pattern of the central nervous system parenchyma were observed. CONCLUSIONS: These preliminary data indicate that the use of a transpulmonary ultrasound contrast agent (SH U 508 A) may substantially broaden the spectrum and potential diagnostic utility of transcranial ultrasound by allowing detection of supratentorial peripheral central nervous system arteries, deep cerebral veins, and (through the foramen magnum) the entire vertebrobasilar system, including the cerebellar arteries.

Adult↗

PubMed1993

Autocrine growth regulation in neuroectodermal tumors as detected with oligodeoxynucleotide antisense molecules.

The cell lines of three neuroectodermal tumors, two glioblastomas (HTZ-146, HTZ-17) and one melanoma (HTZ-19) were established and screened for the expression of growth factors by northern blotting and immunochemical methods. All three tumors were positive for platelet-derived growth factor- (PDGF-) A-, -B-chain, and basic fibroblast growth factor (bFGF) messenger ribonucleic acids. Cultured cells as well as original tumor material were also positive for PDGF-AA-, PDGF-BB, and bFGF protein, as shown by immunochemistry. To investigate the possible pathophysiological role of PDGF and bFGF, antisense technology was employed with chemically modified nuclease-stable 14-mer phosphorothioate oligodeoxynucleotides. Proliferation of all three tumors was reduced to a different extent with antisense phosphorothioate oligodeoxynucleotides in vitro, targeted against PDGF-A-chain-, -B-chain-, and -bFGF-messenger ribonucleic acid. These data indicate autocrine stimulatory loops for PDGF and bFGF, which may be blocked, may have different relevance in neuroectodermal tumors in vitro, and may have conceivable future therapeutic implications.

Biopsy↗

PubMed1993

The effect of transforming growth factor-beta 2-specific phosphorothioate-anti-sense oligodeoxynucleotides in reversing cellular immunosuppression in malignant glioma.

This in vitro study was aimed at restitution of transforming growth factor (TGF)-beta 2-mediated suppression of T-lymphocyte activation within malignant gliomas. In early-passage tumor cell cultures of two glioblastomas (HTZ-153 and HTZ-209) and one malignant astrocytoma classified as World Health Organization Grade III (HTZ-243), autologous peripheral blood mononuclear cells were activated by interleukin-1 alpha and interleukin-2 in vitro (lymphokine-activated killer cells) and tested for cytotoxic and proliferative activity. In expression studies (Western blot and Northern hybridization) of all three tumors, TGF-beta could be detected at the protein and messenger ribonucleic acid (mRNA) levels. A polyclonal anti-TGF-beta neutralizing antibody did not enhance lymphocyte proliferation upon stimulation with tumor targets (3H-thymidine incorporation) and slightly stimulated lymphocyte cytotoxicity against autologous target cells. Preincubation of target cells for 12 hours with TGF-beta 2-specific phosphorothioate-anti-sense oligodeoxynucleotides (S-ODN's) did, however, enhance lymphocyte proliferation up to 2.5-fold and autologous tumor cytotoxicity up to 60%, compared to controls not treated with S-ODN's. Incubation of tumor cells with TGF-beta 2-specific S-ODN's resulted in decreased TGF-beta-specific immunoreactivity in cultured glioma cells, in reduced TGF-beta 2 protein concentration (Western blot), and in a change in the expression pattern of TGF-beta 2 mRNA's. These observations may have implications for in vivo and in vitro activation of a cellular immune response against autologous malignant glioma cells.

Antigens, CD↗

PubMed1993

Imaging of the vertebrobasilar system by transcranial color-coded real-time sonography.

The vertebrobasilar system was investigated in 75 persons by TCCS to evaluate the applicability and diagnostic capacity of this transcranial Duplex technique. Transforaminal and transtemporal acoustic windows were employed to identify the vertebral arteries, basilar artery (PCA) and major branches of the vertebrobasilar system. The frequency of identifying the basilar artery and the PCA ranged from 84 to 94% but was poor for the distal segment of the basilar artery (45.3%). The origin of the basilar artery was disclosed by transcranial Duplex sonography at an average depth of 7.0 cm (range 6.0 to 8.0 cm). The assignment of the obtained flow signals to specific vascular segments was improved by this new technique. In addition, four persons received a maximum of six intravenous injections of a transpulmonary stable sonographic contrast agent (SHU 508 A) to enhance Doppler signal intensity derived from the vertebrobasilar system. The vascular trunk and all major branches of the vertebrobasilar system were identified in these four persons. We conclude that TCCS of the vertebrobasilar system will improve reliability of transcranial sonographic examination.

Basilar Artery↗

PubMed1992

Bromodeoxyuridine hypersensitivity of metastatic melanoma cells.

A model system for testing the efficacy of chemotherapy protocols for metastatic melanoma was established using cell cultures from two brain and three lymph node metastases of melanoma from five different patients. Continuously growing cultures which were positive for tyrosinase activity were analysed regarding their proliferation rate by continuous bromodeoxyuridine (BrdU) labelling and subsequent Hoechst-33258/ethidium bromide flow cytometry. Melanoma cell cultures exhibit a strong sensitivity to BrdU: at 5% oxygen, 50% growth inhibition is attained with 360 +/- 130 microM BrdU (range: 130-520; n = 11) vs 650 +/- 50 microM BrdU (n = 3) for diploid human fibroblasts and 570 +/- 20 microM BrdU (n = 6) for human lymphoid cell lines. Moreover, BrdU sensitivity of melanoma cells is clearly oxygen dependent: 50% growth inhibition at 200 +/- 55 microM (range: 65-400 microM) for 20% oxygen vs 360 +/- 130 microM BrdU for 5% oxygen. The cell cycle kinetic mechanism of BrdU-induced growth inhibition is accumulation of cells in the first cycle G2 phase. On the basis of these results we suggest testing BrdU in chemotherapy protocols for the treatment of metastatic melanoma.

Brain Neoplasms↗

PubMed1992

Purification and analysis of growth regulating proteins secreted by a human melanoma cell line.

Supernatants of a human malignant cell line established from a CNS metastasis, contained several proteins with putative growth regulating functions. BioGel P-10 gel filtration chromatography, reverse phase HPLC purification, and amino-terminal sequencing of purified peptides resulted in characterization of beta 2-microglobulin (beta 2M, 10 kD), ubiquitin (6 kD), and tissue inhibitor of metalloproteinases 2 (TIMP-2, 21 kD). In addition, CNBr cleavage and purification of resulting peptides revealed diazepam binding inhibitor (DBI, 8 kD) and melanoma inhibiting activity (MIA, 11 kD). The secretion of beta 2M as part of the HLA-class I complex may be related to impaired autologous anti-tumour immune function; ubiquitin may play a role in activation or deactivation of extracellular proteins or cell-cell interactions. As HTZ-19 cells respond in a dose-dependent manner to midozolam, DBI may interfere with growth regulation mediated by diazepam receptor sites. In a collagenolytic assay, TIMP-2 interfered with metalloproteinase functions, which are required for degradation of collagen type IV and organotopic metastasis. MIA is clearly associated with a proliferation inhibiting effect on HTZ-19 cells. In conclusion, although this tumour shows a degree of progression, several proteins with putative functions at different cellular levels were identified, related to proliferation as well as to the type of metastasis.

Amino Acid Sequence↗

PubMed1992

Transcranial color-coded real-time sonography in the evaluation of intracranial neoplasms and arteriovenous malformations.

Transcranial color-coded real-time sonography (TCCS) was performed in 57 patients with primary intracranial brain tumors (n = 49) or arteriovenous malformations (n = 8) to evaluate its diagnostic potential. In 46 patients (81%), lesions could be identified employing this technique. In 7 patients, transcranial ultrasound examination was not feasible because of bone thickness; in the remaining 4 patients, the tumor was indistinguishable from adjacent brain tissue despite sufficient insonation, suggesting that these neoplasms are isoechogenic. The sonographic features of brain tumors were very similar: a hyperechogenic matrix of the lesion was interspersed by hypoechogenic pixels. Larger hypoechogenic areas (0.5-1 cm) gave evidence of tumor necrosis. Differences between the findings of TCCS and computed tomography concerning tumor size were found in 7 patients, in whom TCCS revealed an area of smaller extension within the corresponding hypodense area on the computed tomographic scan. Perifocal brain edema could not be detected by ultrasound examination. In 13 patients, a thin, hypoechogenic peritumoral halo was disclosed that did not correlate with perifocal brain edema identified by computed tomography and that may have been due to compression of adjacent parenchyma. In patients with arteriovenous malformations, TCCS permitted the identification of the main feeders, the nidus, and the draining venous system by color-coded depiction of intravascular blood flow. In conclusion, TCCS is an additional method for initial diagnosis and highly suitable for follow-up in tumor patients and provides valuable information about tissue characteristics and blood flow.

Adult↗

PubMed1992

Continuous-pressure controlled, external ventricular drainage for treatment of acute hydrocephalus--evaluation of risk factors.

Experience with a continuous-pressure controlled, external ventricular drainage system (EVD) in 100 patients (n = 49 female, n = 51 male; mean age, 56.3 yr) with acute hydrocephalus is reported. Cerebrospinal fluid circulation disturbances resulted from hemorrhages caused by subarachnoid hemorrhage (n = 45), parenchymal hemorrhages from angioma (n = 4), anticoagulants (n = 7), or hypertension or other reasons (n = 30); in addition, hydrocephalus developed from infections (n = 3), tumors (n = 2), infratentorial infarction (n = 5), or unknown reasons (n = 4); 52 patients had ventricular hemorrhages. No patient died of system-associated morbidity. Mean time of EVD treatment was 9.5 days, with 40 patients being treated for 10 to 29 days; routine refobacin (5 mg) flushing of the system was performed three times a day. Patients without cerebrospinal fluid leakage had a 2% rate of secondary infection compared with 13% in patients with cerebrospinal fluid leakage due to ventricular catheter placement (P < 0.05; overall infection rate, 5%). A clinical mortality rate of 29% during EVD treatment was observed in subarachnoid hemorrhage patients (Hunt and Hess Grades II, III, IV, and V; n = 9, 9, 18, and 9, respectively); recurrent hemorrhages during EVD treatment occurred in 19 patients (26 hemorrhages), and of these, 10 patients died. System occlusion was seen in 19 cases (12 of 45 patients with subarachnoid hemorrhage), requiring catheter and system renewal in 1 case; system extraction was seen in 3 cases, misplacement was seen in 11 cases, and disconnection was seen in 5 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebrospinal Fluid Pressure↗

PubMed1991

Real-time sonography of acute and chronic muscle denervation.

Presented are real-time ultrasound findings in partially and completely denervated muscles of 30 patients with focal neuropathy and various other disorders of the second motor neuron. Sonographic scans of affected muscles are analyzed in conjunction with unaffected muscles of the same individual, under identical examination conditions. Initial pathological ultrasound changes could be detected as soon as 2 weeks after an acute neurogenic lesion. In denervation, the echodensity of the muscle was high and the normal intramuscular pattern was decomposed. Findings were more intense in severe and longstanding denervation. Ultrasound-indicated pathology correlated highly (chi-square: P less than 0.001) with pathological spontaneous activity detected by electromyography. Focal and systemic neuropathies showed no differences in ultrasound pathology. Six cases with central motor palsy had normal sonograms. Poor spatial resolution of real-time ultrasonography--as compared with CT and MRI--is compensated by its bedside availability, frequent repeatability without patient risk and discomfort, and its in vivo correlation of muscle morphology with muscle function.

Adult↗

PubMed1991

In vitro studies on drug interaction of ifosfamide and ACNU in primary and metastatic human brain tumours.

Combination chemotherapy is widely employed in clinical oncology; however, there is no generally accepted model to evaluate individual tumour susceptibility to a given drug combination protocol. We therefore investigated the drug interaction of ifosfamide (4-hydroxyperoxy-ifosfamide) and ACNU in a recently developed in vitro model of paired sequential combination chemotherapy in primary and metastatic malignant brain tumours. A long-term standard [6,3-3H]-thymidine-incorporation assay, employing a liquid scintillation counting protocol, was selected to assess the drug sensitivity of human tumours. In vitro drug exposures were derived from correlating in vivo-(systemic and CNS) and in vitro-pharmacokinetic drug parameters. In combination experiments tumour cells were treated sequentially by two drugs in both sequences: drug exposures were calculated for 2 h with a 1-h drug-free interval in between. "Cut-off" concentrations (maximum in vitro exposure doses) were calculated as 1.74 microM (for primary CNS tumours: 0.58 microM) for ifosfamide and 5.4 microM (for primary CNS tumours: 1.33 microM) for ACNU. Dose/response relations were derived from isotope incorporation rates after cells had grown for approximately five population doubling times. Combination isoboles were plotted after drug doses had been transformed into "equieffective doses", enabling comparison of drug combination effects. In all three glioblastomas (with CNS exposure dose) an additive or supra-additive effect could be observed in either sequence (in one tumour a biphasic additive isobole was found for both sequences). Out of three bronchial carcinomas (small-cell type, brain metastases) in two non-identical sequences a supra-additive effect was observed in two tumours, with antagonistic effects in the third tumour. In all three malignant melanomas and in one renal carcinoma antagonistic effects were observed, whereas in a second renal carcinoma supra-additive effects were demonstrated for both sequences. We conclude that drug combination chemotherapy effects at the cellular level may be extremely heterogeneous.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

[Transcranial color-coded real-time sonography in the adult. 1: Normal findings and cerebrovascular ischemia].

Transcranial colour-coded real time sonography (TCCS) is a new, non-invasive diagnostic bedside procedure allowing two-dimensional imaging of cerebral parenchymatous structures and large intracranial arteries through the intact skull. So far we examined a population of 183 patients und 53 normal subjects, all above 18 years of age. 24 (10%) subjects were not suitable for examination. Two-dimensional imaging of telencephalic, diencephalic, mesencephalic and pontine structures is feasible. Intravascular blood flow phenomena may be analysed quantitatively by an integrated pulsed wave Doppler system. The diagnosis of arterial stenosis and occlusion could be established in 14 patients each by analysing the colour-coded B-mode image and Doppler frequency spectrum. TCCS may complement diagnostic tools in neurology and may improve standardisation of transcranial Doppler measurements.

Adult↗

PubMed1991

[Transcranial color-coded real time sonography in adults. Part 2: Cerebral hemorrhage and tumors].

We examined three groups of adult patients to evaluate the clinical application of transcranial colour-coded real-time sonography (TCCS): 28 patients suffering from intracerebral haemorrhage, 36 patients with subarachnoid haemorrhage and 38 patients with primary brain tumours. All sonographic examinations were performed through the intact skull. Cerebral haemorrhages were visualised via TCCS as hyperechogenic areas, which were closely correlated in size and location to CT findings. Apart from the imaging of subarachnoid haemorrhages and cerebral vasospasms, TCCS permitted the identification of the angiographically confirmed aneurysms in 76%. Brain tumours were delineated in the vast majority of the patients examined. In this type of pathology TCCS provided additional information on tumour extension and macroscopic appearance.

Adult↗

PubMed1991

Diagnosis and monitoring of subarachnoid hemorrhage by transcranial color-coded real-time sonography.

Thirty-six patients with acute spontaneous subarachnoid hemorrhage (26 caused by rupture of an aneurysm) were examined by transcranial color-coded real-time sonography by using a 2.25-MHz ultrasound transducer. In 20 of these 26 patients (76%), the aneurysm could be identified by a characteristic abnormal blood flow pattern within the aneurysm in coronal and axial scanning planes by transcranial color-coded real-time sonography. Blood within the basal cisterns, on top of the tentorium, and within the ventricles and parenchyma was sonographically detected by increased echodensity in 75%. In addition, cerebrospinal fluid circulation disturbances and cerebral vasospasm were detected in two-dimensional B-mode images in 85% and 100%, respectively. In Doppler mode, intravascular blood flow velocity could be quantified. We conclude that transcranial color-coded real-time sonography, a new, noninvasive method for diagnosis and follow-up of patients with subarachnoid hemorrhage, allows detection of the primary vascular lesion and monitoring of complications.

Blood Flow Velocity↗