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C Becker

Publications and source records attributed to C Becker.

At least 37 records · Page 2Linked to original sources
PubMed1998

IL-12 and IL-18 differentially regulate the transcriptional activity of the human IFN-gamma promoter in primary CD4+ T lymphocytes.

We analyzed the molecular mechanisms by which IL-12 and IL-18 induce transcriptional activity of the IFN-gamma promoter in primary human CD4+ T cells. In transfection experiments, we found that IL-18 directly induces IFN-gamma promoter activity, whereas significant activation with IL-12 required costimulation with alphaCD3/CD28. Furthermore, IL-12 caused in vivo protection of a STAT4 (-236) binding site, whereas stimulation with IL-18 or IL-12 plus alphaCD3/CD28 induced occupancy of a downstream AP-1 site. Mutation of this AP-1 site abrogated both IL-12- and IL-18-mediated promoter activation, whereas mutation of the STAT site inhibited IL-12-dependent activation. These data suggest that both AP-1 and STAT4 are required for IL-12-dependent IFN-gamma promoter activity, whereas IL-18 causes direct activation via AP-1. This differential activation of the IFN-gamma promoter gives further insights into molecular pathways governing Th1 T cell development and differentiation.

Base Sequence↗
PubMed1998

A comparison of digital luminescence mammography and conventional film - screen system: preliminary results of clinical evaluation.

The objective of this study was to determine if digital luminescence mammography can be used as a diagnostic tool. We investigated twenty-two patients with mammographically suspicious findings using a conventional film-screen system and a digital phosphor storage plate in order to compare these two techniques. Four radiologists experienced in mammography reviewed each pair of images. Our results indicate that detectability of microcalcifications and solid masses with digital systems is superior to conventional film-screen mammography due to the increased contrast enhancement associated with digital systems. We did, however, find that characterization of morphological details is inferior with the digital system, presumably due to reduced spatial resolution. In addition, we found no statistically significant difference in the differentiation of benign from malignant lesions with both techniques. The accuracy of mammographic diagnosis was investigated in a receiver operating characteristic study and similar values were found with both techniques. Our results indicate that digital mammography will become an acceptable diagnostic tool although improvement, especially in spatial resolution, is desirable.

Aged↗
PubMed1998

Polysialic acid on the neural cell adhesion molecule correlates with expression of polysialyltransferases and promotes neuroblastoma cell growth.

Neuroblastomas and cell lines derived from these tumors bear the oncodevelopmental antigen polysialic acid (PSA) bound to the neural cell adhesion molecule. Polysialyation of neural cell adhesion molecule can be achieved by two different polysialyltransferases, ST8SiaII and ST8SiaIV. This study was undertaken to investigate the pattern of polysialyltransferases expressed in the human neuroblastoma cell line SH-SY5Y. Reverse transcription-PCR showed simultaneous expression of the two enzymes, and in situ hybridization demonstrated that the polysialyltransferase mRNA expression parallels immunoreactivity with the PSA-specific monoclonal antibody 735. After retinoic acid-induced differentiation, only the PSA-positive, neuron-like cell type gave clear signals for ST8SiaII and ST8SiaIV in in situ hybridization, whereas both signals were drastically reduced in the weakly PSA-positive substrate adherent phenotype. Like the SH-SY5Y cells, a primary, PSA-positive neuroblastoma specimen revealed expression of the two polysialyltransferases. To investigate the role of PSA for cell growth and differentiation, SH-SY5Y cells were treated with the PSA-specific endo-N-acetylneuraminidase E. Although loss of PSA was accompanied with a marked reduction of cell growth, it did not interfere with retinoic acid-induced differentiation. Together, our results suggest that PSA surface expression is regulated on the level of polysialyltransferase transcription. Moreover, the similarity to the primary neuroblastoma tissue makes SH-SY5Y cells a suitable model system to examine further the role of polysialylation in tumor cell growth and the orchestration of PSA synthesis in neuroblastoma.

Cell Differentiation↗
PubMed1998

Determination and analysis of antigenic epitopes of prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2) using synthetic peptides and computer modeling.

Prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2), produced essentially by the prostate gland, are 237-amino acid monomeric proteins, with 79% identity in primary structure. Twenty-five anti-PSA monoclonal antibodies (Mabs) were studied for binding to a large array of synthetic linear peptides selected from computer models of PSA and hK2, as well as to biotinylated peptides covering the entire PSA sequence. Sixteen of the Mabs were bound to linear peptides forming four independent binding regions (I-IV). Binding region I was localized to amino acid residues 1-13 (identical sequence for PSA and hK2), II (a and b) was localized to residues 53-64, III (a and b) was localized to residues 80-91 (= kallikrein loop), and IV was localized to residues 151-164. Mabs binding to regions I and IIa were reactive with free PSA, PSA-ACT complex, and with hK2; Mabs binding to regions IIb, IIIa, and IV were reactive with free PSA and PSA-ACT complex, but unreactive with hK2; Mabs binding to region IIIb detected free PSA only. All Mabs tested (n = 7) specific for free PSA reacted with kallikrein loop (binding region IIIb). The presence of Mabs interacting with binding region I did not inhibit the catalytic activity of PSA, whereas Mabs interacting with other binding regions inhibited the catalysis. Theoretical model structures of PSA, hK2, and the PSA-ACT complex were combined with the presented data to suggest an overall orientation of PSA with regard to ACT.

Amino Acid Sequence↗
PubMed1998

[Virtual and three-dimensional bronchoscopy with spiral and electron beam computed tomography].

PURPOSE: To compare spiral computed tomography (CT) and electron-beam CT (EBT) for 3D and virtual CT-bronchoscopy. MATERIALS AND METHODS: 17 patients with various disorders of the tracheobronchial system were examined using fiberoptic bronchoscopy, spiral CT and EBT. 3D images were reconstructed from CT data sets using automated segmentation based on volume-growing methods. Surface-rendered, volume-rendered, and hybrid reconstructions were visualized in real time using a data helmet. RESULTS: All data sets could be processed to high-quality three-dimensional (3D) and virtual reconstructions. The reduction of motion artifacts due to shorter scan times made EBT data sets better suited for automated segmentation and less susceptible to motion artifacts. 3D and virtual reconstructions did not increase the diagnostic sensitivity of CT compared to axial reconstructions alone. CONCLUSIONS: Shorter scan times of CT imaging yield higher-quality 3D and virtual reconstructions. Modern reconstruction techniques are valuable visualization tools for select indications and are the prerequisite for future developments in computer-aided medicine.

Bronchial Neoplasms↗
PubMed1998

[Virtual colonoscopy using CT and MRI].

PURPOSE: To evaluate experimentally and in patients the sensitivity and effective dose of virtual electron-beam tomography (EBT) colonoscopy for detecting small colon tumors and to compare the methods and results with virtual colonoscopy using spiral CT and MR imaging in a review of the literature. MATERIALS AND METHODS: Six polyps with diameters between 3 and 12 mm were created and randomly placed in resected pig colon. After distension with air, the pig colon was scanned with continuous volume scanning (CVS, 3 mm collimation) and a pitch of 0.4, 0.8 and 1.5. Twenty patients positive for the fecal blood test were examined after rectal CO2 insufflation and i.v. administration of 1 mg glucagon. A 13 s CVS scan was used to cover the entire colon within one breath-hold. 3D volume-rendered fly-throughs were evaluated by two independent radiologists. Effective dose equivalent was estimated using an Alderson phantom equipped with thermoluminescence dosimeters. RESULTS: In the tumor model, all polyps were detectable at a pitch of 1.5. A further reduction of the pitch ratio did not improve the conspicuity of the polyps. In patient studies, all tumors (n = 4) and polyps (n = 3) were correctly identified on 3D fly-throughs. Two false positive results were obtained. Effective dose equivalent was calculated at 3.2 mSv per scan. CONCLUSIONS: Our preliminary results indicate that virtual EBT colonoscopy holds promise for fast screening for colon polyps. The best technique for virtual colonoscopy (Spiral CT, EBT, MRI) has not yet been determined and the future role of virtual colonoscopy must still be defined.

Colonic Polyps↗
PubMed1998

[Significance of calcium detection with electron-beam tomography in coronary disease].

PURPOSE: Coronary calcium is a powerful indicator of arteriosclerosis and can be detected very precisely with electron beam tomography. The method can be applied in patients with known coronary artery disease or in asymptomatic patients at risk of arteriosclerotic disease. METHODS: The standard protocol of EBT consists of 30 to 40 slices of 3-mm thickness with a scan time of 100 ms, no overlap. No contrast medium is needed. The total scan can be performed within one breathhold. The calcium score is calculated as described by Agatston. Radiation exposure amounts to 0.8 mSv per total screen. We used spiral CT with and without ECG trigger as an alternative. RESULTS: At the University of Munich we performed an EBT scan of the heart in 1100 patients within the last year. In 567 patients coronary angiography was performed also (+/- 3 days). Confirming previous reports in the literature, we found a correlation of the calcium score with the age and gender of the patients. Severe coronary artery disease (stenoses > or = 75%) was associated with significantly more calcium than less severe CAD. The calcium score did not discriminate between one-, two- and three-vessel disease. The site of calcification does not correlate with the localization of stenoses. Thirty-three percent of the patients with significant coronary artery disease showed a normal age-adjusted calcium score; a total of 8.1% of patients with severe stenoses did not reveal any coronary calcification (score = 0). With asymptomatic patients there are only a few studies available. Soft plaques cannot be detected with EBT, but in most patients soft plaques occur together with hard plaques. Our results show that spiral CT of the newest generation may also be used for calcium screening. There was an excellent correlation of the calcium scores of EBT and spiral CT at all levels of calcification. DISCUSSION: Coronary calcium is a sensitive marker of coronary artery disease. In the clinical setting EBT is indicated in patients with known coronary artery disease (to evaluate prognosis), in patients who are unable to perform a stress test, and in patients with atypical chest pain. However, lack of calcification may be associated with severe stenoses in a minority of patients. The clinical value in asymptomatic patients needs to be defined: randomized studies are necessary. We see a possible indication in patients with known risk factors, in whom primary preventive strategies could be performed more selectively and cost-effectively.

Adolescent↗
PubMed1998

[Significance of electron-beam tomography in the evaluation of the patency of aortocoronary bypasses].

PURPOSE: Electron beam tomography (EBT) permits acquisition of images with high spatial and temporal resolution. The value of EBT and other imaging modalities for the depiction of patent coronary artery bypass grafts (ACVB, IMA) are compared to coronary angiography and an overview of current results is given. MATERIAL AND METHODS: Graft patency can be evaluated with indirect methods stress, such as echocardiography, radionuclide ventriculography, myocardial scintigraphy, positron-emission tomography (PET) and direct imaging modalities, such as Doppler/2D echocardiography, EBT, spiral computed tomography (SCT) and magnetic resonance angiography (MRA). RESULTS: With indirect methods graft patency can be evaluated with sensitivity of 64-100% and specificity of 73-100%. EBT and SCT are equivalent in sensitivity (= 94%) in the assessment of open venous grafts and specificity is up to 100%, but EBT is superior in the diagnosis of patent IMA grafts (sensitivity 100% vs 89%). Visualization of high-grade venous bypass stenosis seems possible with EBT. MRA with gradient echo technique is highly accurate in the assessment of patent venous grafts (sensitivity 77-93%) but has limited value in the evaluation of IMAs (sensitivity = 53%). Promising are ultrafast 3D-MRA methods which permit high accuracy (sensitivity = 94-96%) in assessing venous and arterial grafts. DISCUSSION: Indirect imaging methods cannot differentiate between an occluded bypass, progression of coronary artery disease and myocardial infarction. EBT and SCT are equivalent in the diagnosis of open and occluded venous grafts, but EBT is superior in the assessment of patent IMA grafts. Visualization of high-grade venous bypass stenosis seems possible with EBT. MRA techniques, especially ultrafast 3D-MR methods, are highly accurate in the assessment of patent venous and arterial grafts but are still limited to scientific research.

Coronary Artery Bypass↗
PubMed1998

[Functional imaging of the heart with electron-beam computed tomography].

PURPOSE: Electron-beam computed tomography (EBCT) enables examinations with a very short acquisition time of 50 ms and thus permits cardiac imaging without motion artifacts. Utilizing eight detector rings simultaneous image acquisition in up to eight levels and complete imaging of the whole heart is possible. In studies, functional imaging with EBCT was compared to our angiocardiography, echocardiography, radionuclide, ventriculography and magnetic resonance tomography. MATERIALS AND METHODS: ECG-triggered long- and short-axis cine studies were performed with the Imatron C-150 Evolution, acquiring 160 and 156 images at 8 and 12 levels. After manual tracing of epicardial and endocardial borders, ventricular size, ejection fraction, wall-thickening and myocardial mass were calculated. RESULTS: A very high correlation between EBCT and direct determination of right and left ventricle (r = 0.98 and r = 0.99) was demonstrated. Compared to echocardiography, angiocardiography and radionuclide ventriculography, assessment of ventricular function was more precise and more reliable. DISCUSSION: EBCT allows the exact and reliable determination of left and right ventricular function. Also precise assessment of myocardial mass is possible. However, the high radiation exposure and diagnostic effort have to be considered.

Angiocardiography↗
PubMed1998

[Calculation of absolute cerebral blood volume and cerebral blood flow by means of electron-beam computed tomography (EBT) in acute ischemia].

The utility of electron beam computed tomography (EBT) to estimate cerebral blood volume (CBV) and cerebral blood flow (CBF) was evaluated. Eleven patients with suspected acute cerebral ischemia were investigated. The EBT was performed with an acquisition time of 50 ms per slice at eight parallel levels. To compare signal/noise and contrast/noise ratios the data from the EBT investigation were compared to a similar examination on a spiral CT. The signal/noise ratio with EBT was about 30%, the contrast/noise ratio 25% of that with spiral CT. The absolute values of CBV were 4.9 +/- 1.2 ml/100 g (EBT); CBF was 50.5 +/- 7.0 ml/100 g/min in normal contralateral brain tissue. In four patients with proven infarcts on follow-up, the ischemic areas had a CBV ranging from 1.7 to 3.8 ml/100 g, while CBF ranged from 9.4 to 24.5 ml/100 g/min. Using a bolus injection of contrast material, calculation of absolute CBV and CBF is feasible using EBT. Advantages of EBT are the absolute measurements possible and it's multislice capability. Disadvantages, however, are caused by the high image noise, limiting the demarcation of ischemic tissue.

Acute Disease↗
PubMed1998

The impact of vasoactive substances on intraosseous pressure and blood flow alterations in the femoral head: a study based on magnetic resonance imaging.

In beagle dogs, the alterations of intraosseous pressure and blood supply in the femoral head that result from the administration of vasoactive substances were examined, and the changes were documented by magnetic resonance imaging (MRI). Vasoactive substance were infused into the medial and lateral circumflex femoral arteries of 12 beagle dogs. All infusions were done under standardised conditions with simultaneous measurements of venous blood flow and intraosseous pressure distribution in the proximal femur. The drugs were infused in three cycles of 30 min each separated by 30 min recovery periods, followed by MRI examination at the end of each experiment. At an intraosseous pressure of 14.3 (+/- 4.2) mmHg in the femoral head epiphysis (I), 11.6 (+/- 2.7) mmHg in the greater trochanter (II) and 9.3 (+/- 3.2) mmHg in the femoral shaft (III), a baseline flow of 96.2 (+/- 18.8, n = 12) ml/min was measured in the femoral vein. After infusing bradykinin at a concentration of 10(-6) moles, which is commonly known to lead to cerebral and subcutaneous oedema formation by vessel dilatation, the intraosseous pressure increased to (I): 49.1 (+/- 6.2) mmHg, (II): 42.5 (+/- 5.8) mmHg and (III): 38.3 (+/- 7.1) mmHg in the three measured femoral areas (n = 3). After the bradykinin injection, femoral vein flow increased to a peak value of 238.4 (+/- 43.4) ml/min and then dropped to 62.3 (+/- 14.2) ml/min after discontinuation of the bradykinin infusion. In a second and third series of tests, hyperosmolar (20% NaCl) and hypo-osmolar (distilled water) solutions were applied, also resulting in increased but lower mean intraosseous pressure values (17.3 +/- 4.1 and 25.7 +/- 5.1 ml/min, respectively) in all regions. When administering bradykinin, MRI scans taken immediately after completion of the experiment showed substantial oedema in the femoral muscular system, but without any changes of osseous signals in T1- or short time inversion recovery (STIR)-weighted images, nor did any changes occur when solutions of 20% NaCl or distilled H2O were injected. The results of our experiments demonstrate that acute increases of intraosseous pressure do not cause MRI signal alterations. We therefore conclude that in addition to the described pressure increase, other intraosseous alterations must occur to lead to the detectable signal changes found among patients with diagnosed femoral head necrosis. Finally, the short time period between the rise in intraosseous pressure and performing a conventional MRI may be one reason for missing the development of an intraosseous oedema. On the other hand, conventional MRI might have additional disadvantages for detecting intraosseous fluid compared with a dynamic imaging modality.

Animals↗
PubMed1998

Hyperemesis in late pregnancy--should we think of cancer? A case report.

Gastric cancer is unusual during pregnancy. The diagnosis may be delayed because specific symptoms are similar to typical pregnancy associated complaints. Our therapeutic management with palliative chemotherapy and later gastrectomy differs from other known cases, where surgical resection has been the treatment of choice. Surgery appears to have no influence on the prognosis of gastric cancer patients with hepatic metastases.

Adult↗
PubMed1998

Second unrelated bone marrow transplantation without additional conditioning therapy after engraftment failure.

A 37-year-old female highly alloimmunized by multiple transfusions received a sex matched HLA-identical unrelated bone marrow transplant for hypoplastic MDS-RA with moderate myelofibrosis. Conditioning consisted of total body irradiation, cyclophosphamide and ATG, GVHD prophylaxis consisted of CsA, MTX and prednisolone. The CD34+ stem cell content of the first graft was relatively low due to an inadequate harvest. The patient appeared not to have engrafted by day 23 post-BMT. She therefore received a second sex mismatched HLA-identical unrelated bone marrow graft on day 25 after two days of 3.5 mg/kg methylprednisolone from a different donor. Over the ensuing days, the first marrow showed slow engraftment followed by engraftment of the second graft. The first graft was then rejected, as monitored by peripheral blood studies of chimerism. No signs of acute GVHD were observed. Despite successful trilineage engraftment and complete second donor chimerism, the patient died from disseminated toxoplasmosis encephalitis and pneumonia on day +104.

Adult↗
PubMed1998

Heterogeneous expression of the polysialyltransferases ST8Sia II and ST8Sia IV during postnatal rat brain development.

Polysialic acid on the neural cell adhesion molecule is developmentally regulated and has been implicated in the plasticity of cell-cell interactions. The sialyltransferases ST8Sia II and ST8Sia IV are able to catalyze the synthesis of polysialic acid. This study compares the expression of ST8Sia II and ST8Sia IV mRNA during postnatal rat brain development. Northern blot analysis indicated a substantial down-regulation of ST8Sia II from high expression at postnatal day 2 to almost undetectable levels at the age of 6 months. In contrast, the decline of ST8Sia IV content was moderate. In the mature brain, ST8Sia IV is the predominant polysialyltransferase. In situ hybridization of selected brain regions at postnatal days 2, 11, and 21 confirmed the decline of ST8Sia II level in isocortex, hippocampus, and cerebellum. ST8Sia II was not detectable at any time point in the subependymal layer and the layers of the olfactory bulb. Persistent ST8Sia IV expression was localized in the subependymal layer, the glomerular layer of the olfactory bulb, and the granule cell layer of the dentate gyrus and in some widely dispersed cells of the isocortex. The distinct expression patterns of ST8Sia II and ST8Sia IV suggest their differential regulation. As discussed with regard to the persistent polysialic acid expression, ST8Sia IV should receive particular attention in the mature brain.

Aging↗
PubMed1998

Role of NF-kappaB in immune and inflammatory responses in the gut.

NF-kappaB is a pleiotropic transcription factor with key functions in the intestinal immune system. NF-kappaB family members control transcriptional activity of various promoters of proinflammatory cytokines, cell surface receptors, transcription factors, and adhesion molecules that are involved in intestinal inflammation. The perpetuated activation of NF-kappaB in patients with active inflammatory bowel disease suggests that regulation of NF-kappaB activity is a very attractive target for therapeutic intervention. Such strategies include antioxidants, proteasome inhibitors, inhibition of NF-kappaB by adenoviral I kappaB alpha expression vectors, and antisense DNA targeting of NF-kappaB. These approaches will hopefully permit the design of new treatment strategies for chronic intestinal inflammation.

Animals↗
PubMed1998

Differential activation of CD8+ tumor-specific Tc1 and Tc2 cells by an IL-10-producing murine plasmacytoma.

The involvement of counteractive CD8+ T-cell subsets during tumor-specific immune responses was analyzed in a syngeneic murine plasmacytoma model. CD8+ Tc cells against the immunogenic IL-10-producing BALB/c plasmacytoma ADJ-PC-5 can be easily induced by immunization of BALB/c mice with X-irradiated ADJ-PC-5 tumor cells in vivo and in vitro. However, the failure of recipient mice to mount a protective Tc response against the tumor during early stages of a real or simulated tumor growth is not due to immunological ignorance, but depends on the induction of tumor-specific tolerance, involving a population of tumor-induced CD8+ T cells that are able to inhibit the generation of tumor-specific Tc cells in a primary ADJ-PC-5-specific MLTC, using IFN-gamma as a suppressive factor. Whereas most long-term cultivated CD8+ ADJ-PC-5-specific Tc lines produce type-1 cytokines on stimulation, at least two of them, which were derived from a primary MLTC, display a type-2 cytokine spectrum. Furthermore, the primary in vitro Tc response against ADJ-PC-5 cells shows characteristics of a Tc2 response. The Tc response is strictly depending on tumor-derived IL-10. CD8+ Tc cells that are induced in a primary MLTC do not produce IFN-gamma, and the tumor-specific Tc response is enhanced by IL-4 but suppressed by IFN-gamma or IL-12. In contrast, ADJ-PC-5-specific CD8+ Tc cells from immunized mice are IFN-gamma producing Tc1 cells. Since the primary in vitro Tc response against the tumor is suppressed even by the smallest numbers of irradiated ADJ-PC-5-specific Tc1 cells via IFN-gamma, these Tc1 cells behave similar to the suppressive CD8+ T cells that are induced during early stages of ADJ-PC-5 tumorigenesis.

Animals↗