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Biomedical subjects

J Rieger

Publications and source records attributed to J Rieger.

At least 55 records · Page 3Linked to original sources

Supramolecular Structure of Precipitated Nanosize beta-Carotene Particles.

A combination of analytical methods and molecular modeling calculations has provided a detailed picture of the supramolecular and microscopic structure of precipitated lipophilic carotenoids. The nanoparticles have a core/shell structure (see schematic representation) in which the particle core (120 nm) consists of a variety of molecular aggregates of different sizes, and the shell (40 nm) consists of an adsorbed gelatin layer.

Journal Article↗

Failure of taxol-based combination chemotherapy for malignant glioma cannot be overcome by G2/M checkpoint abrogators or altering the p53 status.

In an effort to develop more effective forms of adjuvant chemotherapy for malignant brain tumors, we sought to develop a taxol-based combination chemotherapy regimen for glioma cell lines in vitro. Here, we report that coexposure of LN-229 or T98G glioma cells to taxol and either doxorubicin, camptothecin, cytarabine, or VM26 resulted in antagonistic effects rather than additive or synergistic cytotoxicity. There were no interactions of taxol with the effects of carmustine (BCNU) or vincristine. Antagonism was more prominent in cytotoxic cell death assays than in clonogenic cell death assays and was not overcome by G2/M checkpoint abrogators such as caffeine or pentoxyfilline. Ectopic expression of mutant and wild-type p53val135 attenuated taxol cytotoxicity in both T98G cells, which are mutant for p53, and LN-229 cells, which exhibit functional wild-type p53 activity. Interestingly, wild-type p53val135 abrogated the taxol-imposed G2/M arrest in both cell lines. However, wild-type p53val135 did not promote glioma cell killing by combinations of taxol and any of the other drugs. Further, an analysis of a panel of 12 human glioma cell lines revealed no relationship between genetic or functional p53 status and taxol sensitivity. In summary, combination either with other chemotherapy drugs, with abrogators of the G2/M checkpoint, with wild-type p53 gene transfer was not a promising approach for a taxol-based combination chemotherapy regimen in malignant glioma.

Antineoplastic Combined Chemotherapy Protocols↗

Human astrocytic brain tumors express AP02L/TRAIL.

AP02 ligand (APO2L) is a CD95 ligand (CD95L)-related cytokine of the tumor necrosis factor family that interacts with agonistic (DR4, DR5) and antagonistic (DcR1, DcR2) receptors. Cultured malignant glioma cells preferentially express agonistic receptors and are susceptible to APO2L-induced apoptosis. Here, we report that 8 of 8 human glioma cell lines expressed APO2L mRNA and protein in vitro. Immunohistochemistry using a monoclonal antibody to APO2L revealed that all 23 primary astrocytic brain tumors analyzed, including low-grade astrocytomas and glioblastomas, express APO2L in vivo. With the exception of reactive astrocytes, non-neoplastic glia and neurons in the cerebrum lacked immunoreactivity of APO2L. Thus, in addition to the CD95/CD95L system, a second death ligand/death receptor pair may regulate susceptibility to apoptosis in human glial neoplasms.

Adult↗

[Fat-saturated, contrast-enhanced spin-echo sequences in the magnetic resonance tomographic diagnosis of peritoneal carcinosis].

PURPOSE: To evaluate contrast-enhanced, fat-saturated spin echo sequences for the detection of peritoneal carcinosis with MRI. MATERIALS AND METHODS: 61 patients, 35 with and 26 without peritoneal carcinosis, were examined with abdominal MRI. Fat-saturated, T1-weighted spin echo sequences were performed before and after administration of Gd-DTPA. In addition, 22 patients with peritoneal carcinosis were examined with contrast-enhanced abdominal CT. RESULTS: 32 of 35 patients with peritoneal carcinosis demonstrated contrast enhancement of the visceral and 30 of 35 enhancement of the parietal peritoneum (91 and 86%, respectively). Wall thickening of the intestine or parietal peritoneum were noted in 21 and 20 of 35 patients (60 and 57%, respectively), ascites in 18 of 35 patients (51%). False positive contrast enhancement of the peritoneum was noted in 4 of 26 patients (15%). In the direct comparison of MRI and CT, 22 of 22 patients versus 7 of 22 patients showed contrast enhancement of the visceral peritoneum (100 and 32%, respectively). For other signs of peritoneal carcinosis (e.g., ascites, peritoneal seedings), no differences in diagnostic reliability were demonstrated. CONCLUSIONS: The use of fat-saturated, spin echo sequences facilitates the diagnosis of peritoneal carcinosis by artifact reduction and improved detection of peritoneal contrast enhancement. MRI with fat-saturated sequences was superior to CT.

Adult↗

[Temporary balloon occlusion as therapy of uncontrollable arterial hemorrhage in multiple trauma patients].

PURPOSE: Presentation of temporary balloon occlusion as an interventional radiological method for managing hemorrhage in multiply injured patients with uncontrollable loss of blood. METHOD: Temporary, non-selective arterial occlusion by introduction of a balloon catheter contralaterally to the source of bleeding has been performed since 1992 on 7 patients with multiple injuries, hemorrhagic shock requiring reanimation, and angiographic demonstration of an arterial hemorrhage in the supply region of the internal iliac artery with complex pelvic fracture. In each case a PTA balloon catheter was introduced transfemorally, non-selectively positioned proximal to the bleeding source, and left in place for 24-48 h under manometric control. Control angiographies were performed prior to catheter removal. RESULTS: The bleeding was stopped immediately in all 7 patients. The hemodynamic stability made transport and thus further surgical management and/or a short-term treatment in the intensive-care station possible. Control angiographies confirmed that the bleeding had stopped in all patients. CONCLUSIONS: We recommend temporary balloon occlusion as a rapid and effective method for the management of bleeding in otherwise uncontrollable traumatic hemorrhages in the supply region of the internal iliac artery.

Adult↗

Contrast sensitivity and appearance in briefly presented illusory figures.

We examined the contributions of brightness enhancement, illusory figure formation and figural completion to changes in contrast sensitivity in contour gaps. The brightness on the border of a Kanizsa-square and an outline square was measured as the point of subjective equality with the background (PSE) for small line targets. Increment and decrement thresholds were measured at the same location. We found that contrast thresholds were lower than in a control condition without inducers, and that the threshold reduction was independent of the contrast polarity of the inducers. This reduction cannot be explained by a simple summation of stimulus contrast and induced brightness. In a second experiment the inducers that define the contour of the Kanizsa and the outline square were changed so that the figure was no longer closed, keeping the local stimulus surround constant. Thresholds were equally reduced for all conditions, independently of whether the figure was completed or not, or whether an illusory contour was perceived or not. The results suggest that the reduction of contrast threshold in contour gaps is independent of the brightness perceived in these gaps and of the formation of an illusory figure. Processes that cause contrast threshold reduction in contour gaps also seem to operate independently of figural completion.

Adaptation, Ocular↗

Predicting chemoresistance in human malignant glioma cells: the role of molecular genetic analyses.

Less than 30% of malignant gliomas respond to adjuvant chemotherapy. Here, we asked whether alterations in the p53 and RB pathways and the expression of six BCL-2 family proteins predicted acute cytotoxicity and clonogenic cell death induced by BCNU, vincristine, cytarabine, teniposide, doxorubicin, camptothecin or beta-lapachone in 12 human malignant glioma cell lines. Neither wild-type p53 status, nor p53 protein accumulation, nor p21 or MDM-2 levels, nor differential expression of BCL-2 family proteins predicted drug sensitivity, except for an association of BAX with higher beta-lapachone sensitivity in acute cytotoxicity assays. p16 protein expression was associated with high doubling time and chemoresistance. We conclude that some important molecular changes, which are involved in the development of gliomas and attributed a role in regulating vulnerability to apoptosis, may not determine the response to chemotherapy in these tumors.

Antineoplastic Agents↗

Synthesis and biological effects of NO in malignant glioma cells: modulation by cytokines including CD95L and TGF-beta, dexamethasone, and p53 gene transfer.

Nitric oxide (NO) is thought to play an important role in neurotransmission, inflammation, and regulation of cell death in the mammalian brain. Here, we examined the synthesis and biological effects of NO in human malignant glioma cells. Exposure to cytokines such as interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha or interleukin (IL)-1beta and lipopolysaccharide (LPS) induced NO synthesis in rat C6 and A172 human glioma cells, but not in LN-229, T98G or LN-18 human malignant glioma cells. Induced release of NO involved enhanced expression of inducible NO synthase (iNOS). Failure to detect NO release in the latter cell lines was not overcome by neutralization of endogenous TGF-beta or by coexposure to cytokines, LPS, and antioxidants. Apoptosis induced by CD95 ligand (CD95L) did not involve NO formation. Neither NOS inhibitors nor NO donators modulated CD95L-induced apoptosis. Dexamethasone (DEX)-mediated protection of glioma cells from CD95L-induced apoptosis was also independent of DEX effects on NO metabolism. DEX inhibited not only cytokine/LPS-evoked NO release but also attenuated the toxicity of NO in three of five cell lines. Forced expression of temperature-sensitive p53 val135 in C6 cells in either mutant or wild-type conformation inhibited cytokine/LPS-induced NO synthesis. Further, accumulation of p53 in both mutant or wild-type conformation protected glioma cells from the toxicity of exogenous NO, consistent with a gain of p53 function associated with p53 accumulation. We conclude that resistance to NO-dependent immune defense mechanisms may contribute to the malignant progression of human cancers with p53 alterations, notably those associated with the accumulation of mutant p53 protein.

Animals↗

APO2 ligand: a novel lethal weapon against malignant glioma?

APO2L (TRAIL) is a novel CD95L (Fas/APO-1-L) homologous cytotoxic cytokine that interacts with various receptors which transmit (DR4, DR5) or inhibit (DcR1, DcR2) an apoptotic signal. Here, we report that human glioma cell lines preferentially express mRNAs for agonistic death receptors DR4 (8/12) and DR5 (11/12) rather than the death-inhibitory decoy receptors DcR1 (4/12) and DcR2 (2/12). Ten of 12 cell lines are susceptible to APO2L-induced apoptosis. The resistant cell lines, U138MG and U373MG, are cross-resistant to CD95L-induced apoptosis. Similar to CD95L-induced apoptosis, APO2L-induced apoptosis is inhibited by ectopic expression of the caspase inhibitor, crm-A, or of bcl-2, or by coexposure to the corticosteroid, dexamethasone, or the lipoxygenase inhibitor, nordihydroguaretic acid. There is no correlation between p53 genetic status of the cell lines and their susceptibility to APO2L-induced apoptosis, but the latter is moderately enhanced by ectopic expression of wild-type p53. APO2L targeting may be a promising approach for selectively targeting apoptosis to human malignant glioma cells.

Apoptosis↗

[Dosimetry in conventional and spiral CT in 8 spiral CT scanners of the latest generation].

PURPOSE: Measurement of scanner-dependent differences in PCTDI for conventional and spiral CT and evaluation of PCTDI/100 mAs in eight spiral CT scanners of the latest generation. METHODS: Central PCTDI was evaluated in a PMMA phantom for different scan lengths of conventional and spiral CT in four scanners. Central and peripheral PCTDI/100 mAs, average dose and the quotient between peripheral and central PCTDI/100 mAs were measured with a dedicated 10 cm ionisation chamber positioned within a PMMA phantom using the parameters of a standardised liver protocol and a high-resolution inner ear protocol for eight spiral CT scanners. RESULTS: Depending on scanner type and scan length PCTDI for the spiral mode is in a range between 11.3% higher and 4.3% lower than that for the conventional mode. PCTDI/100 mAs varies considerably between different CT scanners. For the standardised liver protocol PCTDI/100 mAs varies up to a factor of 2, for the inner ear protocol up to a factor of 4. CONCLUSION: Even in comparable modern CT scanners there are considerable protocol and scanner-dependent differences in PCTDI/100 mAs. The values for his own scanner should be known to each CT user so that he can develop a dose-optimised, patient and problem-orientated examination strategy.

Ear, Inner↗

Radiation dose and image quality in spiral computed tomography: multicentre evaluation at six institutions.

The purpose of this study was to evaluate the correlation of radiation dose with image quality in spiral CT. Seven clinical protocols were measured in six different radiological departments provided with four different types of high specification spiral CT scanners. Central and surface absorbed doses were measured in acrylic. The practical CT dose index (PCTDI) was calculated for seven clinical examination protocols and one standardized protocol using identical parameters on four different spiral CT scanners with a dedicated ionization chamber inserted into PMMA phantoms. For low contrast measurements, a cylindrical three-dimensional (3D) phantom (different sized spheres of defined contrast) was used. Image noise was measured with a cylindrical water phantom and high contrast resolution with a Perspex hole phantom. Image quality phantoms were scanned using the parameters of the clinical protocols. Images were randomized, blinded and read by six radiologists (one from each institution). PCTDI values for four different scanners varied up to a factor between 1.5 (centre) and 2.2 (surface) for the standardized protocol. A greater degree of variation was observed for seven clinical examination protocols of the six radiological departments. For example, PCTDI varied up to a factor between 1.7 (cerebrum protocol) and 8.3 (abdomen paediatric protocol). Low contrast resolution correlates closely with dose. An improvement in detection from 8 mm to 4 mm sized spheres needs approximately a ten-fold increase in dose. Noise shows a moderate correlation with PCTDI. High contrast resolution of clinical protocols is independent of PCTDI within a certain range. Differences in modern CT scanner technology seem to be of less importance for radiation exposure than selection of protocol parameters in different radiological institutes. Future discussion on guidelines regarding optimal (patient adapted) tube current for clinical protocols is desirable.

Brain↗

Interpolation processes in the perception of real and illusory contours.

The spatial and temporal characteristics of mechanisms that bridge gaps between line segments were determined. The presentation time that was necessary for localisation and identification of a triangular shape made up of pacmen, pacmen with lines, lines, line segments (corners), or pacmen with circles (amodal completion) was measured. The triangle was embedded in a field of distractors made up of the same components but at random orientations. Subjects had to indicate whether the triangle was on the left or on the right of the display (localisation) and whether it was pointing upward or downward (identification). Poststimulus masks consisted of pinwheels for the pacmen stimuli or wheels defined by lines. Stimuli were presented on a grey background and defined by luminance or isoluminant contrast. Thresholds were fastest when the triangle was defined by real contours, as for the pacmen with lines (105 ms) and the lines only (92 ms), slightly slower for corners (118 ms) and pacmen (136 ms), and much slower for the amodally completed pacmen (285 ms). For all inducer types localisation was about 20 ms faster than identification. In a second experiment the relative length of the gap between inducers was varied. Thresholds increased as a function of gap length, indicating that the gaps between the inducers need to be interpolated. There was no significant difference in the speed of this interpolation process between the pacman stimuli and the line-segment stimuli. About 40 ms were required to interpolate 1 deg of visual angle, corresponding to about one third of the distance between inducers. In a third experiment, it was found that processing of isoluminant stimuli was as fast as for low-contrast luminance stimuli, when targets were defined by real contours (lines), but much slower for illusory contours (pacmen). The conclusion is that the time necessary to interpolate a contour depends greatly on the spatial configuration of the stimulus. Since interpolation is faster for the line-segment stimuli, which do not elicit the percept of an illusory contour, the interpolation process seems to be independent of the formation of illusory contours.

Humans↗

Initial clinical experience with spiral CT and 3D arterial reconstruction in intracranial aneurysms and arteriovenous malformations.

We studied 32 consecutive patients with known or suspected cerebrovascular abnormalities studied with spiral CT following a intravenous bolus injection of iodinated contrast medium with a power injector. Flow was 3 or 4 ml/s. In an attempt to define the appropriate delay time and scan duration a cranial angio-CT without table increment was performed on 10 patients. Enhancement was measured by manually placed regions of interest within the left middle cerebral artery and the inferior sagittal sinus. All patients except one had intraarterial angiography (DSA) for comparison. In 6 patients with an arteriovenous malformation (AVM) follow-up was possible after one and/or two embolisation procedures. These patients had plain and contrast-enhanced spiral CT. The diagnosis was aneurysm in 9 (8 berry aneurysms, one giant fusiform aneurysm), AVM in 13 (all supratentorial) and traumatic arteriovenous fistula in one. In 9 patients there were no detectable pathological vascular findings. After 3D reconstruction the size (between 5 and 28 mm), location and the relationship to the parent vessel of the aneurysms, the extent of the AVMs and the distribution of the embolisation material could be demonstrated clearly. The main feeding vessel(s), nidus and draining veins were reliably shown. The decreased extent of the AVMs after embolisation was clearly demonstrated. There was no difference in diagnosis when DSA and 3D-CT were compared by two independent radiologists. We consider arterial spiral CT with 3D reconstruction to have the potential of offering important diagnostic information for the treatment of intracranial AVMs and aneurysms.

Adult↗

[Studies on radiation exposure in retrograde sclerotherapy of the testicular vein].

PURPOSE: Prospective evaluation of different radiation exposure parameters in a large series of varicoceles. The dependency of the square area product on the different therapists was calculated in addition. MATERIAL AND METHOD: Between 5/91 and 12/93 a total of 737 sclerotherapies were performed on 465 patients. The following parameters were measured prospectively: Square area product (n = 737), fluorotime (n = 737), symphysis surface doses (n = 24), gonadal doses (n = 49), catheterisation time (n = 737). 608 of the sclerotherapies were performed by 4 similar experienced radiologists (U1 - U4). The individual fluorotimes, square area products and the average square area product per minute fluorotime were calculated. RESULTS: The average gonadal doses was 0.01 mSv. Calculation of the square area product per minute fluorotime revealed a useful parameter to demonstrate the potential for further dose reduction, because the results ranged from 566 mGy x cm2/min to 988 mGy x cm2/min. There is no need for a time limit for this interventional procedure. CONCLUSION: The gonadal doses is so low that it can be considered negligible. However, in view of the considerable differences in the square area product per minute, close attention must be paid to the technique by which th fluorotime is determined.

Adolescent↗

Spinal cord sarcoidosis.

We present a case of spinal cord sarcoidosis which resembled a disseminated intramedullary tumour. The case is unusual because the spinal cord is only rarely affected by sarcoidosis and the patient developed a neurological deficit as the first manifestation of the disease. This condition thus has to be considered in the differential diagnosis of primary intramedullary tumours, or metastatic disease with involvement of the spinal cord.

Diagnosis, Differential↗