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Biomedical subjects

T Sommer

Publications and source records attributed to T Sommer.

At least 91 records · Page 5Linked to original sources

Endoplasmic reticulum degradation: reverse protein flow of no return.

The endoplasmic reticulum (ER) is the site of entry of proteins into the secretory pathway. It is responsible for proper folding of the proteins before delivery to their site of action. Furthermore, proofreading to detect malfolded or unnecessary proteins that have to be eliminated and regulation of protein levels are crucial ER functions. The ubiquitin-proteasome system, located in the cytoplasm, has emerged as the major ER degradation machinery. A multitude of ER resident as well as membrane-bound and soluble proteolytic substrates of the secretory pathway are retained in the ER and destined for degradation via this pathway. Their actual proteolysis is preceded by a retrograde transport to the cytoplasm. A key component of the translocation apparatus, Sec61p, is also the central subunit of the retrograde transport system. Other components of the translocon such as Sec63p or the lumenal chaperone BiP may also be involved in export to the cytosol. Novel ER membrane proteins such as Der1p, Der3p/Hrd1p, or Hrd3p might reprogram the translocon for retrograde transport. As ubiquitination is a prerequisite for degradation by the proteasome, exported proteins are ubiquitinated. Representatives of ER membrane-bound ubiquitin-conjugating enzymes, Ubc6p and Cue1p/Ubc7p, have been identified in yeast. Retrograde transport and ubiquitination seem to be coupled processes.

Biological Transport, Active↗

Healthy premenopausal breast parenchyma in dynamic contrast-enhanced MR imaging of the breast: normal contrast medium enhancement and cyclical-phase dependency.

PURPOSE: To define the range of normal contrast medium enhancement, the variability in contrast medium enhancement patterns in healthy premenopausal breast parenchyma, and the implications for management strategies in cases with incidental contrast medium-enhancing foci on breast magnetic resonance (MR) images. MATERIALS AND METHODS: Twenty healthy volunteers (aged 21-41 years) were examined on a 1.5-T system (dynamic two-dimensional gradient-echo protocol with subtraction postprocessing) during each week of a menstrual cycle (group 1) or over 4 months (group 2). The authors evaluated changes in the number of enhancing foci and the respective enhancement patterns within a cycle and between cycles. RESULTS: Both diffuse and nodular enhancement of breast parenchyma occurred during all phases of the menstrual cycle, especially in weeks 1 and 4. Enhancement was lowest in week 2. A total of 60 enhancing foci (73% of which resolved completely during follow-up) were found in 16 of 20 volunteers. Twenty-six foci demonstrated enhancement velocities beyond the malignancy threshold (>80% increase in the 1st minute). CONCLUSION: Contrast-enhancing foci are normal in healthy premenopausal breasts, even when formal malignancy criteria of enhancement velocity are met. This has to be kept in mind to avoid false-positive results, especially in younger patients.

Adult↗

Degradation of subunits of the Sec61p complex, an integral component of the ER membrane, by the ubiquitin-proteasome pathway.

We have investigated the degradation of subunits of the trimeric Sec61p complex, a key component of the protein translocation apparatus of the ER membrane. A mutant form of Sec6lp and one of the two associated proteins (Sss1p) are selectively degraded, while the third constituent of the complex (Sbh1p) is stable. Our results demonstrate that the proteolysis of the multispanning membrane protein Sec61p is mediated by the ubiquitin-proteasome pathway, since it requires polyubiquitination, the presence of a membrane-bound (Ubc6) and a soluble (Ubc7) ubiquitin-conjugating enzyme and a functional proteasome. The process is proposed to be specific for unassembled Sec61p and Sss1p. Thus, our results suggest that one pathway of ER degradation of abnormal or unassembled membrane proteins is initiated at the cytoplasmic side of the ER.

Cell Compartmentation↗

A second trimeric complex containing homologs of the Sec61p complex functions in protein transport across the ER membrane of S. cerevisiae.

Yeast microsomes contain a heptameric Sec complex involved in post-translational protein transport that is composed of a heterotrimeric Sec61p complex and a tetrameric Sec62-Sec63 complex. The trimeric Sec61p complex also exists as a separate entity that probably functions in co-translational protein transport, like its homolog in mammals. We have now discovered in the yeast endoplasmic reticulum membrane a second, structurally related trimeric complex, named Ssh1p complex. It consists of Ssh1p1 (Sec sixty-one homolog 1), a rather distant relative of Sec61p, of Sbh2p, a homolog of the Sbh1p subunit of the Sec61p complex, and of Sss1p, a component common to both trimeric complexes. In contrast to Sec61p, Ssh1p is not essential for cell viability but it is required for normal growth rates. Sbh1p and Sbh2p individually are also not essential, but cells lacking both proteins are impaired in their growth at elevated temperatures and accumulate precursors of secretory proteins; microsomes isolated from these cells also exhibit a reduced rate of post-translational protein transport. Like the Sec61p complex, the Ssh1p complex interacts with membrane-bound ribosomes, but it does not associate with the Sec62-Sec63p complex to form a heptameric Sec complex. We therefore propose that it functions exclusively in the co-translational pathway of protein transport.

Amino Acid Sequence↗

Standardized uptake values of fluorine-18 fluorodeoxyglucose: the value of different normalization procedures.

While the evident advantages of absolute metabolic rate determinations cannot be equalled by static image analysis of fluorine-18 fluorodeoxyglucose positron emission tomographic (FDG PET) studies, various algorithms for the normalization of static FDG uptake values have been proposed. This study was performed to compare different normalization procedures in terms of dependency on individual patient characteristics. Standardized FDG uptake values (SUVs) were calculated for liver and lung tissue in 126 patients studied with whole-body FDG PET. Uptake values were normalized for total body weight, lean body mass and body surface area. Ranges, means, medians, standard deviations and variation coefficients of these SUV parameters were calculated and their interdependency with total body weight, lean body mass, body surface area, patient height and blood sugar levels was calculated by means of regression analysis. Standardized FDG uptake values normalized for body surface area were clearly superior to SUV parameters normalized for total body weight or lean body mass. Variation and correlation coefficients of body surface area-normalized uptake values were minimal when compared with SUV parameters derived from the other normalization procedures. Normalization for total body weight resulted in uptake values still dependent on body weight and blood sugar levels, while normalization for lean body mass did not eliminate the positive correlation with lean body mass and patient height. It is concluded that normalization of FDG uptake values for body surface area is less dependent on the individual patient characteristics than are FDG uptake values normalized for other parameters, and therefore appears to be preferable for FDG PET studies in oncology.

Algorithms↗

[Indirect MR arthrography of the shoulder. An alternative to direct MR arthrography?].

INTRODUCTION: The purpose of this study was to evaluate the diagnostic power of indirect MR arthrography (I-MRA) particularly in rotator cuff tears. MATERIAL AND METHODS: Sonography, conventional MRI and I-MRA were compared with arthroscopy in 25 patients. Additionally literature about experience with the method in other shoulder disease was searched. RESULTS: Sensitivity and specificity in the detection of rotator cuff tears were 0.6 and 0.7 respectively using sonography, 0.66 and 1 with conventional MRI and 1 and 0.86 for I-MRA. I-MRA was especially useful in diagnosing partial tears. In other studies I-MRA showed good results in the evaluation of glenoid labral tears, with a sensitivity of 91% and a specificity of 92%. CONCLUSION: I-MRA can be successfully used to diagnose rotator cuff and labral tears.

Adult↗

[MRI of the pancreas: value of standard versus fat-suppressed pulse sequence at 0.5 T].

PURPOSE: To compare five pulse sequences in 60 patients with pancreatic disease by means of MRI at 0.5 T. METHODS: T1 weighted Spin-Echo sequences (T1W SE) before and after i.v. contrast medium administration, fat-suppressed T1W SE sequences after i.v. contrast medium administration, T2 weighted Turbo-Spin-Echo sequences (T2W TSE), and fat-suppressed T2W TSE were evaluated within an ROC study. RESULTS: The standard sequences (T1W SE before and after i.v. contrast medium administration, T2W TSE) were superior to the fat-suppressed T1W and T2W (T)SE sequences in delineating the anatomy and for correct diagnosis. The T1W sequence with and without i.v. contrast media detected all anatomic structures best. In most instances the correct diagnosis and coexistent findings in the diseased pancreas were obtained with the T2W sequence. CONCLUSION: Fat-suppressed sequences are less useful in the diagnosis of pancreatic disease by MRI at medium field strength compared to the standard sequences.

Diagnosis, Differential↗

[A new application of MR tomography of the lung using ultra-short turbo spin echo sequences].

PURPOSE: Development of an improved MR sequence for examining the lung. METHOD: T2 weighted ultra-short turbo spin echo sequences were used in five individuals with variations in echo times, delayed triggering and echo intervals. To reduce movement artifacts all examinations were carried out with ECG and respiratory triggering. The sequences giving optimal image quality were then employed in 19 patients having various pulmonary abnormalities. Image resolutions, artifacts, image contrasts and diagnostic value were then judged by two observers and compared with CT. RESULTS: In the first study, a diastole-triggered UTSE sequence with the shortest echo proved optimal (TE = 90 ms, TR = 2-4 s, echo = 9 ms, turbo factor = 19). In the patient series studied, MRT was inferior to CT with regard to resolution and number of artifacts, but better in respect of contrast and diagnostic value. CONCLUSION: Using UTSE of the lung, MRT can produce images of good quality. Compared with CT, contrast is better with MRT, offering diagnostic advantages for MRT.

Diagnosis, Differential↗

[Standardization and acceleration of quantitative analysis of dynamic MR mammographies via parametric images and automatized ROI definition].

PURPOSE: To evaluate quantitative analysis of dynamic breast MRI studies using a dedicated PC based diagnosis system (DS) providing parametric images and automatic ROI definition as compared to the standard subtraction image, manual-ROI based procedure. METHODS: We compared the diagnostic usefulness of parametric versus subtraction images in terms of visualisation of enhancement inhomogeneities and enhancement velocities. Quantitative analysis of enhancing lesions of 15 breast MRI studies was performed using both the DS and the system's console software (SC). We assessed the time needed for complete quantitative analysis and number of lesions evaluated. This was followed by assessment of within-reader and between-reader variability or within-case reproducibility of results of quantitative analysis. RESULTS: Parametric images are superior to subtraction images in visualizing enhancement inhomogeneities or ring enhancement in breast cancers. Mean time needed for analysis at DS and SC was 4 (3-5) min. and 23 (8-39) min., respectively. During this time period, significantly more lesions were evaluated per case using the DS as compared to the SC (2-14 vs. 1-6). Mean within-reader variability of enhancement velocities of the same lesions was 0% and 25% (DS and SC); between-reader variability of enhancement values obtained in the same lesions was 11% (DS) versus 41% (SC). CONCLUSION: The DS significantly cuts down the time needed for quantitative analysis. It significantly improves reproducibility of quantitative enhancement values due to standardization of ROI analysis.

Adult↗

[Intramural hematoma of the thoracic aorta: diagnostic imaging and differential diagnosis].

PURPOSE: Aortic wall thickening due to intramural hemorrhage may be the only sign of aortic dissection. The aim of this study was to evaluate the incidence, imaging features and differential diagnoses of intramural hemorrhage (IMH) of the thoracic aorta. METHODS: 98 patients with clinically suspected aortic dissection were investigated via Spiral-CT and MRT. Diagnosis of IMH based on the presence of smooth crescentic or concentric wall thickening over a longer segment of the thoracic aorta without flow visualization and without compression or distortion of the aortic lumen. RESULTS: 69 patients had classic aortic dissections and 7 patients were diagnosed to have IMH of thoracic aorta. One patient with IMH of the ascending aorta died of aortic rupture and subsequent pericardial tamponade 12 hours after onset of symptoms. In one patient with IMH of the descending aorta on initial examination, there was a progression of overt aortic dissection at follow-up after three weeks. In two patients with IMH of the descending aorta, wall thickening decreased in size at follow-up (10-15 weeks), whereas in one patient it remained unchanged. CONCLUSION: IMH of the aorta should be considered a precursor of aortic dissection. At follow-up IMH may decrease in size, rupture or progress to overt aortic dissection.

Adult↗

Possible causes of a positive Haemoccult-II test in a population screening study for colorectal neoplasia.

In a population study for colorectal neoplasia possible relationships were sought between faecal occult bleeding and clinical findings. Samples were taken from three different stools, collected during biennial screening from 1985 to 1994 in the age group 45-75 years at the beginning of the study. A total of 943 persons had positive Haemoccult-II (H-II) tests in at least one of the five screening rounds, and 87% had a complete colonoscopy. Of the 20,672 persons accepting initial screening, 1% had a positive test, the figure increasing to 1.8% during the fifth screen. The degree of positivity (1-3 slides) decreased with time. Positive tests were most frequent in men. Predictive values (PVpos) for colorectal cancer (CRC) increased with increasing number of positive slides from 6 to 31%. The average PVpos decreased from 17% during the initial screen to 8% during the fifth. Average PVpos for possible precursors (adenomas) varied from 40% at the beginning to 33% at the end. PVpos for CRC and inflammatory bowel disease increased when visible blood in the stools was present. Marcoumar increased PVpos for adenomas. Colorectal examination in the 943 persons revealed 114 persons with CRC and further 377 with adenomas. Early CRC (Dukes' stage A) was detected in 46 of the 114 with CRC, a more favourable distribution than that found in symptomatic patients. The study defined a group of people with a high risk of colorectal neoplasia, with a good prognosis, out of a group who had been selected at random from a normal population.

Aged↗

Aortic dissection: a comparative study of diagnosis with spiral CT, multiplanar transesophageal echocardiography, and MR imaging.

PURPOSE: To compare the usefulness of spiral computed tomography (CT), multiplanar transesophageal echocardiography (TEE), and magnetic resonance (MR) imaging in the diagnosis of thoracic aortic dissection and arch vessel involvement. MATERIALS AND METHODS: Forty-nine symptomatic patients with clinically suspected aortic dissection were examined with contrast material-enhanced spiral CT, multiplanar TEE, and 0.5-T MR imaging (T1-weighted, cardiac-gated, spin-echo sequences). Imaging results were confirmed at autopsy (five patients), intraoperative exploration (23 patients), angiography (nine patients), and follow-up (12 patients). RESULTS: Sensitivity in the detection of thoracic aortic dissection was 100% for all techniques. Specificity was 100%, 94%, and 94% for spiral CT, multiplanar TEE, and MR imaging, respectively. In the assessment of aortic arch vessel involvement, sensitivity was 93%, 60%, and 67%, respectively, and specificity was 97%, 85%, and 88%, respectively. CONCLUSION: Spinal CT and multiplanar TEE are as valuable as MR imaging in the detection of thoracic aortic dissection. In the assessment of the supraaortic branches, spiral CT is superior (P<.05).

Adult↗

Indirect MR arthrography: optimization and clinical applications.

PURPOSE: To evaluate and optimize a method for producing magnetic resonance (MR) images similar to MR arthrograms of multiple synovial joints with intravenous gadopentetate dimeglumine injection. MATERIALS AND METHODS: The authors examined the effects of joint motion, dose of gadopentetate dimeglumine (0.1, 0.2, and 0.4 mmol/kg), and fat saturation on the enhancement rate of the joint cavity and the degree of image contrast generated among articular structures on MR images in 14 healthy volunteers. Shoulder, elbow, wrist, hip, knee, and ankle joints of 10 volunteers were imaged with optimized parameters. Indirect MR arthrographic findings in 17 patients with joint disorders (eg, rotator-cuff tears, meniscal tears, and osteoarthritis) were compared with arthroscopic findings. RESULTS: Fat-saturated images obtained after 10 minutes of exercise and administration of 0.1 mmol/kg gadopentetate dimeglumine were similar to those obtained after intraarticular injection of contrast medium. Exercising the joint yielded the strongest joint-cavity enhancement. Increasing the dose of contrast medium in the unexercised joint did not statistically significantly improve the contrast-to-noise ratio. Rotator cuff tears, meniscal tears, and cartilage defects were better delineated with this method than with unenhanced MR imaging and showed good correlation with arthroscopic results. CONCLUSION: Indirect MR arthrography of an exercised joint provides homogeneous enhancement and improved delineation of soft-tissue structures.

Adult↗

[Spiral computerized tomography, multiplane transesophageal echocardiography and magnetic resonance imaging in the diagnosis of thoracic aortic dissection].

The aim of this study was the evaluation of spiral computed tomography (Spiral-CT), multiplane transesophageal echocardiography (multiplane TEE) and magnetic resonance imaging (MRI) in the diagnosis of thoracic aortic dissection. 41 patients were examined: 30 with clinically suspected acute aortic dissection (14 Stanford A, 7 Stanford B), 11 with aortic repair (7/11 with persisting distal dissection). In 14 patients there was involvement of the supraaortic vessels. Sensitivity of Spiral-CT, multiplane TEE and MRI in the detection of aortic dissection was 100%, specificity was 100, 92, and 91%. In the assessment of involvement of aortic arch vessels sensitivity was 100, 67, and 60%, specificity was 100, 95, and 90%. The new imaging modalities Spiral-CT and multiplane TEE are equal to MRI in the detection of aortic dissection. In the assessment of the supraaortic branches Spiral-CT is superior to multiplane TEE and MRI and might become the method of choice.

Adult↗

[Turbo-spin-echo (TSE) sequences with selective fat suppression (SPIR) compared with chemical shift sequences in MRI for differentiation of adrenal tumors. Spectral Presaturation by Inversion Recovery].

AIM: The value of chemical-shift-gradient-echo sequences and turbo-spin-echo sequences with selective fat suppression (SPIR = Spectral Presaturation by Inversion Recovery) in the differentiation of benign and malignant adrenal tumours was investigated. METHODS: Both techniques were performed at 1.5 T in 22 patients with 24 tumours. The loss of signal intensity of the tumour or of the signal intensity ratio between tumour and liver or muscle on the opposed phase Fast-Field-Echo (FFE) sequence in comparison to the in phase FFE sequence or on the TSE-SPIR sequence compared to the TSE sequence was the criterion for intratumoral lipid, suggesting a benign mass. RESULTS: The sensitivity and specificity of the chemical shift technique was 62-77 and 100%, respectively. In adrenal tumours larger than 1.5 cm sensitivity of the chemical-shift technique was 89%. On the contrary sensitivity of the TSE-SPIR sequence was only 11-78%. Both techniques had a specificity of 100%. CONCLUSION: The chemical shift technique is more accurate in the differentiation of adrenal masses than the TSE-SPIR sequence.

Adenoma↗