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Bettina Jung

Publications and source records attributed to Bettina Jung.

6 recordsLinked to original sources

Autoimmunity as a result of escape from RNA surveillance.

In previous studies, we detected a frame shift mutation in the gene encoding the autoantigen La of a patient with systemic lupus erythematosus. The mutant La mRNA contains a premature termination codon. mRNAs that prematurely terminate translation should be eliminated by RNA quality control mechanisms. As we find Abs specific for the mutant La form in approximately 30% of sera from anti-La-positive patients, we expected that mutant La mRNAs circumvent RNA control and the expression of mutant La protein could become harmful. Indeed, real-time PCR, immunostaining, and immunoblotting data of mice transgenic for the mutant La form show that mutant La mRNAs are not repressed in these animals and are translated to mutant La protein. In addition to the mutant La protein, we detected a minor portion of native human La in the mutant La-transgenic mice. Therefore, ribosomal frame shifting may allow the mutant La mRNA to escape from RNA control. Interestingly, expression of the mutant La mRNA results in a lupus-like disease in the experimental mice. Consequently, escape of mutant La mRNA from RNA control can have two effects: it 1) results in the expression of an immunogenic (neo)epitope, and 2) predisposes to autoimmunity.

3T3 Cells↗

Molecular modeling directed synthesis of a bicyclic analogue of the delta opioid receptor agonist SNC 80.

In order to find novel delta opioid receptor agonists, the pharmacophoric benzhydryl moiety of the lead compound SNC 80 (1) was dissected and the phenyl residues were attached to different positions of the 6,8-diazabicyclo[3.2.2]nonane core system (4). The position of the carboxamido group, the stereochemistry, the C3/C4 bond order and the kind and length of the spacer X were considered. The resulting compounds were compared with the four energetically most favourable conformations of SNC 80 by a multifit analysis. These calculations led to the structures 5-10, which fit best to SNC 80. Herein the synthesis of one of these compounds (9) is described. Starting from (S)-glutamate two alternative routes are detailed to obtain the key intermediate 14. A variation of the Dieckmann cyclization, which uses trapping of the first cyclization product with ClSiMe(3) provided the mixed acetal 20, which was carefully hydrolyzed to yield the bicyclic ketone 17. Stereoselective addition of phenylmagnesium bromide, dehydration, LiAlH(4) reduction and exchange of the N-6 residue afforded the designed compound 9. The affinities of 9 towards delta, mu, kappa and ORL1 receptors were determined in receptor binding studies with radioligands. Only moderate receptor affinity was found.

Animals↗

Is postcontrast trueFISP imaging advantageous?

RATIONALE AND OBJECTIVES: Contrast of trueFISP images depends mainly on the T2/T1 ratio. Consequently, there is a potential gain in signal intensity after administration of paramagnetic contrast medium despite the strong T2 weighting. The purpose of this study was to analyze signal intensities of abdominal organs after applying contrast medium and to determine whether this yields an improved contrast for pathologies compared with precontrast trueFISP. MATERIALS AND METHODS: Fifty patients underwent an abdominal examination, including the trueFISP sequence before and after the administration of contrast medium. All images were obtained with a 1.5 T system. The mean signal-to-noise ratio before and after contrast medium was assessed for abdominal organs, vessels, muscle, and fat. The contrast-to-noise ratio (CNR) of pathologic lesions was calculated. RESULTS: The trueFISP sequence yielded a higher signal-to-noise ratio after application of contrast medium for all organs except for fat and the aorta. CNR of solid lesions (angiomyolipoma, liver adenoma, liver hemangioma, hepatocellular carcinoma) increased whereas contrast of cysts decreased. CONCLUSIONS: TrueFISP imaging after application of contrast medium led to better CNR for many solid lesions while cysts showed a diminished contrast. We advise trueFISP imaging sequences before and after contrast medium application.

Abdomen↗

Measurement of cardiac output from a test-bolus injection in multislice computed tomography.

The aim of this study was to assess the feasibility of non-invasive determination of cardiac function from test-bolus data in multislice spiral computed tomography (MSCT). In 25 patients enhancement data gathered from a standardized test-bolus injection were analyzed. The test-bolus examination was performed prior to a retrospectively ECG-gated MSCT of the heart. A time-attenuation curve was obtained in the ascending aorta at the level of the pulmonary arteries. A gamma variate fit was applied to the curve in order to exclude recirculation and get pure first-pass data. Using the known amount of iodine injected, cardiac output (CO), and stroke volume (SV) were determined from integration of the fitted contrast enhancement curve using a reformation of the Stewart-Hamilton equation. Results were compared with CO and SV calculated from the geometric analysis of the retrospectively gated MSCT data using the ARGUS Software (Siemens, Forchheim, Germany). The CO and SV determined from test-bolus analysis and from geometric analysis correlated well with Pearson's correlation coefficients of 0.87 and 0.88, respectively. The standard deviation of the difference between both methods was 0.51 l/min for CO (8.6%) and 11.0 ml for SV (12.3%). Non-invasive quantification of CO seems to be feasible from a standard test-bolus injection. It provides valuable information on cardiac function without additional radiation or application of contrast material.

Cardiac Output↗

A new algorithm for metal artifact reduction in computed tomography: in vitro and in vivo evaluation after total hip replacement.

RATIONALE AND OBJECTIVES: To evaluate a newly developed algorithm for metal artifact reduction (MAR) in Computed Tomography (CT). METHODS: A projection interpolation algorithm for MAR with threshold-based metal segmentation was developed. First, the algorithm was tested with a simulated hip phantom. On demand, the presence of metallic inserts was simulated, representing total hip endoprostheses. Second, CT data of 20 patient with total hip endoprosthesis were reconstructed with and without application of the MAR algorithm. Image quality was independently assessed by 2 experienced radiologists using a qualitative score. The results of the in vitro study were evaluated with the Student's t test. Results of the in vivo study were analyzed using a repeated-measure analysis of variance. RESULTS: Applying the MAR algorithm the phantom study showed no significant difference between images with and without simulated metal contributions. The patient study revealed improved image quality using the MAR algorithm. Results were statistically significant for fat (P=0.0097), vessels (P=0.0091), and bone (P=0.0005). Improvement of the image quality for muscle was not statistically significant (P=0.0287). CONCLUSIONS: A new algorithm for metal artifact reduction was successfully introduced into clinical routine. The algorithm led to a robust reduction of metal artifacts. The MAR algorithm may serve for an improvement in image quality in patients with metallic implants.

Aged↗

[An unusual cause of pulmonary fibrosis in a 71-year-old patient].

CASE REPORT: A 71-year-old woman, suffering from spinal stenosis presented interstitial lung disease, albinism, and severe loss of visual acuity. On physical examination she showed tic-like automatism predominantly periorbital in the face and in the fingers. A computed tomography of the chest revealed typical findings of interstitial lung disease and additional mediastinal lymphomas and ground-glass attenuation in the lower regions of the lung. The findings of a transbronchial lung biopsy, presenting alveolar macrophages with ceroid-like material and platelet function studies proving slightly impaired platelet aggregation confirmed the clinical diagnosis of Hermansky-Pudlak syndrome. Sufficient pain control could be achieved without surgery and the patient was discharged home. 11 months after discharge, severe dyspnea and fever developed and finally the patient died of respiratory failure. CONCLUSION: The Hermansky-Pudlak syndrome is a rare cause of interstitial lung disease. In general, the lung disease presents in younger patients, but it may emerge in the elderly as well. Alveolar macrophages containing ceroid-like material are typical findings in BAL or lung biopsy. Furthermore impaired platelet aggregation and bleeding diathesis may be present. Both findings are useful to identify this rare disorder.

Aged↗