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Biomedical subjects

T Sommer

Publications and source records attributed to T Sommer.

At least 19 recordsLinked to original sources

NIP domain prevents N-type inactivation in voltage-gated potassium channels.

Shaker-related voltage-gated K+ (Kv) channels are assembled from ion-conducting K(v)alpha subunits, which are integral membrane proteins, and auxiliary K(v)beta subunits. This leads to the formation of highly diverse heteromultimeric Kv channels that mediate outward currents with a wide range of time courses for inactivation. Two principal inactivation mechanisms have been recognized: C-type inactivation correlated with carboxy-terminal K(v)alpha-subunit structures, and N-type inactivation conferred by 'ball' domains in the amino termini of certain K(v)alpha and K(v)beta subunits. Assembly of heteromultimers with one or more K(v)alpha- and/or K(v)beta ball domains appears to be an essential principle of the generation of A-type Kv channel diversity. Here we show that, unexpectedly, the presence of K(v)alpha- or K(v)beta-ball domains does not dominate the gating phenotype in heteromultimers containing Kv1.6alpha subunits. These heteromultimers mediate non-inactivating currents because of the dominant-negative activity of a new type of N-type inactivation-prevention (NIP) domain present in the Kv1.6 amino terminus. Mutations in the NIP domain lead to loss of function, and its transfer to another K(v)alpha subunit leads to gain of function. Our discovery of the NIP domain, which neutralizes the activity of K(v)alpha- and K(v)beta-inactivation gates, establishes a new determinant for the gating behaviour of heteromultimeric Kv channels.

Amino Acid Sequence

Indirect MR arthrography: techniques and applications.

Indirect MR arthrography is a relatively new MR technique improving articular and periarticular contrast. It is achieved by injection of paramagnetic MR contrast media intravenously instead of intra-articular injection as in direct MR arthrography. After the injection exercising the joint results in considerable signal intensity increase within the joint cavity. Fat saturated MR sequences then yield arthrographic images. The method is less invasive than direct MR arthrography and first results showed comparable sensitivities and specificities for rotator cuff and glenoid labrum pathology. In this article the technique, established and potential future indications, drawbacks and limitations of the method are reviewed.

Contrast Media

[Löffler fibroblastic endocarditis in the thrombotic stages in isolated right ventricular tissue eosinophilia].

We report on a male, 31 year old, Turkish patient with an intracardiac mass in the right ventricle, reduction of performance and weight, as well as intermittent fever. No eosinophilia was documented in the peripheral blood; cardiac function was primarily normal. Besides the differential diagnosis of Löffer's endocarditis (endomyocardial fibrosis) an inflammatory disease and a malignant cardiac tumor were suggested. The diagnosis of Löffler's endocarditis could not be confirmed morphologically by echocardiography nor histologically by right ventricular biopsy. Operative removal of the mass lesion was necessary because of fast tumor progression, fulminant pulmonary embolism, and infiltration of the tricuspid valve. Only then, histologically Löffler's eosinophilic endocarditis of thrombotic stage was diagnosed. Antiphlogistic therapy with cortisone was initially performed. With a dose reduction after 6 months, a relapse of the thrombotic mass occurred. Therefore, continuous treatment with cortisone and azathioprine was induced followed by further tumor regression and further clinical stabilization since 8 months of treatment.

Adult

[A rational study of the great abdominal veins using 2D-TOF- and turbo-spin-echo sequences].

PURPOSE: Development of a fast and reliable protocol for the detection and exclusion of abdominal venous thrombosis with an optimised T2-TSE- and 2D-TOF sequence. MATERIAL AND METHOD: Evaluation of the flow-void phenomenon with a flow phantom on a 1.5 and 0.5 Tesla system using different echo times. Examination of 22 patients with suspected abdominal shunt- or abdominal vein-thrombosis with a optimum T2-TSE- and 2D-TOF sequence with a 1.5 or 0.5 Tesla system. Confirmation of thrombosis with contrast-enhanced computed tomography or digital subtraction angiography. RESULTS: The most effective combination of strong flow-void phenomena, signal/noise ratio and scan time was found with the following parameters: TE 120 ms, TR 2000 ms, 5 mm slice gap. In the patient group two complete and two partial thromboses were diagnosed with both sequences. One wrong positive thrombosis occurred in a stenotic anastomosis with the 2D-inflow sequence. CONCLUSION: With optimum parameters the T2-TSE sequence produces a strong "flow-void" phenomenon suitable for "black-blood"-MRA. The use of this sequence alone or in combination with 2D-inflow MRA, if "bright-blood" MRA is recommended, allows a reliable evaluation of thrombosis in abdominal veins without high-tech MRA equipment and contrast media.

Abdomen

[Quantitative evaluation of the suitability of magnetic resonance sequences for the detection of spinal bone marrow metastases of solid tumors].

AIM: To compare MR sequences for the examination of the bone marrow of the spine in the detection of skeletal metastases. METHODS: 20 standardised prospective studies of the cervical, thoracic or lumbar spine in patients with known skeletal metastases were evaluated quantitatively. Studies included T1w SE with and without intravenous contrast medium (CM) administration of Gd-DTPA, T2w TSE with and without frequence selective fat saturation (SPIR), opposed phase gradient echo (opGE) with and without intravenous CM administration of Gd-DTPA and T1w SE CM SPIR sequences. The quantitative parameters signal/noise ratio (SNR), contrast/noise ratio (CNR) and contrast were evaluated. RESULTS: OpGE with contrast showed the best results in SNR, CNR and C. Results were statistically significant. Good SNR and C also was found for T1w SE native. SPIR and T2w sequences were less sensitive. CONCLUSION: OpGE sequences are recommended for the detection of skeletal metastases of the spine.

Bone Marrow Neoplasms

[MRI in patients with cardiac pacemakers: in vitro and in vivo evaluation at 0.5 tesla].

PURPOSE: MRI is currently regarded as absolutely contraindicated in patients with implanted cardiac pacemakers. In this prospective study safety and feasibility of MRI in patients with new generation pacemakers (PM) was evaluated in vitro and in vivo. METHODS: 14 PM models in vitro and 18 patients with implanted new generation PM underwent a MRI exam at 0.5 Tesla with standard spin, turbo spin, and gradient echo (FFE) sequences under continuous ECG-monitoring. PM inquiry was performed before and after the MRI exam, including assessment of stimulation thresholds. RESULTS: In the static magnetic field all PM switched to the asynchronous mode due to activation of the Reed switch, resulting in continuous pacing at a fixed rate. In three PM models in vitro, however, after activation of the Reed switch, there was a software-induced switch back to the demand mode. In these PM inhibition and triggering were observed after starting the MRI scan due to influence of the pulsed magnetic fields. PM program changes, damage of PM components, dislocation/torque of the PM and rapid pacing of the PM were observed neither in vitro nor in vivo. Atrial and ventricular stimulation thresholds remained unchanged. CONCLUSION: MRI at 0.5 Tesla should not be regarded as absolutely contraindicated in patients with implanted new generation PM. However, knowledge of the behaviour of the specific PM model in static and pulsed magnetic fields is required, if necessary also changes of the PM program prior to the MRI exam, continuous ECG monitoring and cardiological stand-by.

Contraindications

[Spiral CT and MRT of the operated Stanford-type-A aortic dissection: its course and complications].

PURPOSE: To demonstrate normal postoperative spiral CT and MRI findings and typical complications in patients with aortic repair after Stanford type A aortic dissection. METHODS: 24 patients with aortic repair after Stanford type A aortic dissection were followed up by spiral CT and MRI (0.5 Tesla). Presence of persistent dissection, progressive or new dissection, proximal and distal anastomosis, periprosthetic space, supraaortic vessels, thrombosis and dilatation of the true and false lumen were evaluated. RESULTS: The following postoperative complications were seen: three pseudoaneurysms which developed at the proximal anastomoses of the Dacron prosthesis in two cases and at the insertion site of the reimplanted left coronary artery after implantation of a composite graft (Bentall procedure) in one case; one re-dissection; one perforation of the false lumen; periprosthetic flow in one patient after surgical repair of type A dissection by the graft inclusion technique; progressive dilatation of the false lumen in 4 cases; dilatation of the aortic root in a Marfan patient after replacement of the ascending aorta. CONCLUSION: Precise knowledge of the surgical technique performed is crucial to accurate postoperative imaging evaluation. MRI is the method of choice in the postoperative follow-up of clinically stable patients with aortic dissections.

Aortic Dissection

[MRI in typical and atypical aortic dissection].

PURPOSE: To determine the value of MRI in typical and atypical aortic dissections. METHODS: MRI investigations on 16 patients with aortic dissections were analysed retrospectively; for 8 patients CT investigations carried out at almost the same time were available for comparison. RESULTS: In all cases the diagnosis of aortic dissection was possible from MRI and CT. If a dissection membrane and a double lumen were present these were detected in all patients by both methods. In three patients with atypical dissections, only an asymmetrical abnormal wall thickening as sole sign for the presence of an aortic dissection was seen. A differentiation between true and false lumen was possible in 16 of 17 MRI investigations and in 5 of 8 CT investigations on the basis of differing blood flow velocities or, respectively, the detection of a thrombus in the false lumen. The relationship of the dissection membrane to the large aortic branches as well as the determination of the branch vessel origin with regard to true or false lumen could be evaluated better with MRI than with CT. CONCLUSIONS: Thus MRI has a significant role in the diagnosis and follow-up of aortic dissections. The advantage in comparison to the alternative spiral CT technique is, in addition to the absence of radiation exposure, the better analysis of the extent of the dissection as a result of the multi-planar slice orientation (especially in the region of the aortic arch and the arch vessel origins) without the necessity to administer iodine-containing contrast media.

Adult

Role of Cue1p in ubiquitination and degradation at the ER surface.

Endoplasmic reticulum (ER) degradation of aberrant proteins is mediated by the ubiquitin-proteasome pathway. Here, a membrane-bound component of the ubiquitin system, Cue1p, was identified. It was shown to recruit the soluble ubiquitin-conjugating enzyme Ubc7p to the ER membrane. In the absence of Cue1p, unassembled and thus cytosolically mislocalized Ubc7p was unable to participate in ER degradation or in the turnover of soluble non-ER proteins. Moreover, ubiquitination by Cue1p-assembled Ubc7p and Ubc6p was a prerequisite for retrograde transport of lumenal substrates out of the ER, which suggests that ubiquitination is mechanistically integrated into the ER degradation process.

Amino Acid Sequence

Mutant analysis links the translocon and BiP to retrograde protein transport for ER degradation.

Proteins enter the secretory pathway through the endoplasmic reticulum, which delivers properly folded proteins to their site of action and contains a quality-control system to monitor and prevent abnormal proteins from being delivered. Many of these proteins are degraded by the cytoplasmic proteasome, which requires their retrograde transport to the cytoplasm. Based on a co-immunoprecipitation of major histocompatibility complex (MHC) class I heavy-chain breakdown intermediates with the translocon subunit Sec61p, it was speculated that Sec61p maybe involved in retrograde transport. Here we present functional evidence from genetic studies that Sec61p mediates retrograde transport of a mutated lumenal yeast carboxypeptidase ycsY (CPY*) in vivo. The endoplasmic reticulum lumenal chaperone BiP (Kar2p) and Sec63p, which are also subunits of the import machinery, are involved in export of CPY* to the cytosol. Thus our results demonstrate that retrograde transport of proteins is mediated by a functional translocon. We consider the export of endoplasmic reticulum-localized proteins to the cytosol by the translocon for proteasome degradation to be a general process in eukaryotic cell biology.

Biological Transport

Diagnostic value of MR imaging in comparison to CT in the detection and differential diagnosis of renal masses: ROC analysis.

The aim of this work was to compare MR imaging and CT in the detection of renal masses and in the differential diagnosis between benign and malignant lesions. In 33 patients with 54 renal lesions CT and MR images were evaluated by four readers with regard to tumor detection and characterization using a receiver-operating-characteristics (ROC) analysis. The MRI protocol consisted of a T1-weighted spin-echo (SE) sequence (TR/TE: 300/10 ms) before and after contrast administration and a heavily T2-weighted turbo-SE (TSE) sequence (TR/TE: 5500/150 ms). Az values for the area under the ROC curves for lesion detection were 0.92 +/- 0.04 for CT and 0.91 +/- 0.05 for MRI, respectively, which was not statistically different. The MRI technique was slightly, but not significantly, better than CT in the overall characterization (accuracy in differentiation between benign and malignant) of renal lesions with an Az value of 0.90 +/- 0.05 compared with 0.88 +/- 0.06 for CT. The MRI technique proved to be statistically superior to CT (p < 0.01) in the correct characterization of benign renal lesions. MRI equals CT in the overall detection and differential diagnosis of renal masses. MRI is very helpful for further differential diagnosis of lesions which are equivocal on CT especially in the differentiation between complicated cysts and cystic or hypovascular renal cell carcinoma.

Adult

Indirect MR arthrography: techniques and applications.

Indirect MR arthrography is a simple noninvasive alternative to direct MR arthrography and can potentially alter the diagnostic work-up of several diseases. Based on current knowledge, these diseases include rotator cuff tears. glenoid labrum tears, recurrent tears of the menisci and classification of osteochondritis dissecans. The technique is recommended for inclusion in the MRI diagnostic array, and may obviate the need for invasive direct MR arthrography. The technique and applications of indirect MR arthrography are summarized in this article, based on our own experiences and that described in the current literature.

Adipose Tissue

[The biceps-/rotator cuff-index in ultrasound diagnosis of chronic rupture of the rotator cuff].

PURPOSE: Diagnosis of old lesions of the rotator cuff is clinically and sonographically challenging. To improve the sonographic diagnosis of old rotator cuff tears the index was developed. METHOD: In a prospective study 100 patients were examined by ultrasound to evaluate standard measures of rotator cuff diameters in relation to the long biceps tendon. The compensating hypertrophy of the biceps tendon was sonographically quantified in relation to the rotator cuff diameter. RESULTS: The pathological study group included 50 patients with an old lesion of rotator cuff (> 3 months). The control group consisted of 50 patients without any lesions. Comparison of both groups revealed a significantly higher biceps/rotator cuff ratio (p < 0.05). Data higher than 0.8 represent a pathological ratio (Index positive), the standard is 0.5. The index is independent of sex and age. There are no significant index changes measurable in acute tears of the rotator cuff. CONCLUSION: The index helps to improve sensitivity in diagnosis of old rotator cuff tears by ultrasound.

Adult

[Indirect MR arthrography in the diagnosis of lesions of the labrum glenoidale].

PURPOSE: It has been shown that intravenous administration of contrast media produces an MR arthrographic effect without the need for intraarticular injection. This is the first study evaluating this new technique of indirect MR arthrography in the diagnosis of glenoid labrum tears. METHODS: 28 patients with clinically suspected labral injuries were prospectively investigated (1.5 Tesla, flexible surface coil). A plain MR examination of the shoulder (transverse and oblique-coronal orientation, T1-weighted spin- [TE/TR 15/675], proton density- and T2*-weighted gradient echo [TE/TR/Flip 14,32/600/30 degrees] sequences) and indirect MR arthrography (transverse and oblique-coronal orientation, fat-suppressed T1-weighted spin-echo sequences [TE/TR 15/675], intravenous injection of gadopentetate dimeglumine [0.1 mmol/kg], followed by 10-15 min of joint movement) were performed. Results were confirmed by arthroscopy and/or open surgery. RESULTS: Indirect MR arthrography significantly improved delineation of the glenoid labrum and hyaline cartilage (p < 0.05). Sensitivity and specificity of indirect MR arthrography in the diagnosis of labral injuries were 90% and 89%, compared to 79% and 67% of the native MR examination. CONCLUSION: Indirect MR arthrography is a promising non-invasive technique in the evaluation of the glenoid labrum.

Adult

[MR relaxation time measurements with and without selective fat suppression (SPIR) in endocrine orbitopathy].

PURPOSE: To determine the value and utility of relaxation time measurements with magnetic resonance (MR) imaging in patients with Graves' ophthalmopathy (G.O.). MATERIALS AND METHODS: 20 orbits were studied in control subjects and 58 orbits in patients with G.O. T2 relaxation times of extraocular muscles and retrobulbar fat tissue were calculated. The thickness of the eye muscles was correlated with the calculated T2 times. 18 orbits were measured before and after retro-orbital radiation therapy. RESULTS: Upper limits of determined normal T2 values were 60 ms in extraocular eye muscles and 40 ms in retrobulbar fat tissue. 89% (17/19) of the patients with G.O. had prolonged T2 times in extraocular eye muscles. The retrobulbar fat tissue in 5 of 38 orbits revealed minimal edema with the use of fat saturated sequences. T2 relaxation times decreased significantly (p < 10(-4)) after 10 Gy radiation therapy. No correlation was found between enlargement and T2 relaxation times in extraocular eye muscles (r = 0.44 in patients before radiation therapy). CONCLUSION: In patients with G.O. the determination of the enlargement of extraocular eye muscles in computed tomography is not a sufficient parameter for an antiinflammatory therapy, since CT cannot visualise eye muscle edema. T2 relaxation time measurements with MR imaging allow differentiation between edematous and fibrotic changes. This is the diagnostic method of choice in patients with Graves' ophthalmopathy.

Adipose Tissue