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Biomedical subjects

M Thelen

Publications and source records attributed to M Thelen.

At least 145 records · Page 8Linked to original sources
PubMed1998

Inactivation and dephosphorylation of protein kinase Balpha (PKBalpha) promoted by hyperosmotic stress.

To study the role of protein kinase B (PKB) in response to cellular stress, we examined PKBalpha activity following different stress treatments. Hyperosmotic but not chemical stress resulted in inactivation of PKBalpha and prevented activation by pervanadate and mitogens. Hyperosmotic shock did not affect the MAP kinase pathway, suggesting that this inhibitory effect was specific for PKB. Our data further indicate that downregulation occurs via dephosphorylation of Thr308 and Ser473, the major regulatory phosphorylation sites of PKBalpha. Indeed, calyculin A, which inhibits protein phosphatases 1 and 2A, effectively blocked hyperosmotic stress-mediated inactivation (dephosphorylation) of PKBalpha. High osmolarity did not affect phosphatidylinositol 3-kinase activity but led to a marked increase in PI(3,4,5)P3 and a decrease in PI(3,4)P2 formation after pervanadate stimulation, suggesting that hyperosmotic stress has an inhibitory effect on a phosphatidylinositol 5-phosphatase which converts PI(3,4,5)P3 into PI(3,4)P2. Immunofluorescence studies revealed that membrane translocation, a prerequisite for PKB activation, was not affected by hyperosmotic stress. Our results indicate that hyperosmotic stress can act at two levels: (i) inhibition of phosphorylation of Thr308 and Ser473 by upstream kinases and (ii) by promoting rapid dephosphorylation of these regulatory sites.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed1998

Caspase-mediated proteolysis during apoptosis: insights from apoptotic neutrophils.

Apoptosis is initiated by activation of caspases (interleukin 1beta-converting enzyme homologues), which cause coordinated cleavage of several death substrates that function in structural or homeostatic pathways. The relationship between substrate cleavage and apoptosis is not yet known, nor is it clear whether cleavage of specific substrates is a critical requirement for apoptosis. The human neutrophil provides novel insights into the roles of proteolysis of specific substrates during apoptosis, since only a subset of caspase substrates are present in mature neutrophils. Of the death substrates we screened, PARP, the nuclear mitotic apparatus protein (NuMA), the 70 kDa subunit of the U1 small ribonucleoprotein (U1-70kDa) and the catalytic subunit of DNA-dependent protein kinase (DNA-PK(CS)) were not detected in non-apoptotic neutrophils; in contrast, lamin B and fodrin were present in amounts similar to those found in other cells. Caspase-3 activity was absent in freshly isolated neutrophils, but was detected when neutrophils were aged in vitro, coincident with the onset of morphologic and biochemical apoptosis. The absence of PARP, NuMA, U1-70kDa and DNA-PK(CS) in non-apoptotic neutrophils suggests that these are not critical anti-apoptotic proteins, and that their fragments are not required components of the neutrophil apoptotic pathway. These studies highlight the conserved role of caspase activation in the apoptotic mechanism, and focus attention on several conserved structural substrates as potential transducers of the proteolytic signal in apoptosis.

Apoptosis↗
PubMed1998

Pulmonary nodules: detection with low-dose vs conventional-dose spiral CT.

The purpose of the study was the evaluation of low-dose spiral CT in the detection and assessment of contours of pulmonary nodules. In a prospective investigation 71 consecutive chest CT examinations were acquired both at 30 and 200 mA. Films were interpreted independently by two radiologists. According to the size, nodules were divided into four categories: </= 3, 4-5, 6-10, and > 10 mm; nodule shape was registered. With both protocols, 240 nodules were detected. The correlation coefficient for both methods was 0.89. Discrepancies were found most frequently in nodules near to pulmonary vessels. Nodule size estimation did not differ more than one size category. Eight spiculated nodules were identified by both techniques. Low-dose spiral CT of the chest has a high sensitivity in the detection of pulmonary nodules. If clinical circumstances require dose minimization, low-dose spiral CT may be advocated as an alternative screening method to conventional dose spiral CT.

Adolescent↗
PubMed1998

Detection of coronary artery calcifications predicting coronary heart disease: comparison of fluoroscopy and spiral CT.

The aim of this study was to evaluate the clinical relevance of coronary artery calcifications detected by spiral CT, congruence with fluoroscopy (FS) and coronary angiography, and comparison with studies reporting on application of double-helical CT and ultrafast CT. Forty patients underwent spiral CT (2-mm slice thickness, table feed 3 mm/s), coronary angiography, and FS (performed in the usual manner). Stenosis and calcifications were evaluated semiquantitatively. Nineteen patients suffering from a stenosis >/= 75 % were verified at coronary angiography. All had coronary artery calcification on spiral CT. Fluoroscopy did not detect 8 of 19 patients with a stenosis >/= 75 % (1 vessel: n = 1; 2 vessels: n = 3; 3 vessels: n = 4). In spiral CT sensitivity was 100 % and specificity was 33 % (FS: 58 and 48 %). Positive predictive value was 83 % for spiral CT (FS: 50 %), and negative predictive value was 100 % (FS: 56 %). A significant linear increase in the calcification score was found for increasing maximal stenosis (p < 0.005). Spiral CT is more sensitive than FS in the recognition of hemodynamic relevant stenoses using the detection of coronary artery calcifications. Statistical parameters are comparable to ultrafast-CT. Spiral CT is a suitable non-invasive diagnostic technique in coronary heart disease. Coronary calcifications found incidentally in symptomatic patients at chest CT should be reported to the referring physician for further cardiological workup.

Adult↗
PubMed1998

Bone age determination based on the study of the medial extremity of the clavicle.

The development of the medial clavicular epiphysis and its fusion with the clavicular shaft have been a subject of medical research since the second decade of this century. Computed tomography provides the imaging modality of choice in analyzing the maturation process of the sternal end of the clavicle. In a retrospective study, we analyzed normal development in 380 individuals under the age of 30 years. The appearance of an epiphyseal ossification center occurred between ages 11 and 22 years. Partial union was found from age 16 until age 26 years. Complete union was first noted at age 22 years and in 100 % of the sample at age 27 years. Based on these data, age-related standardized age distributions and 95 % reference intervals were calculated. Compared to the experience recorded in the relevant literature, there are several landmarks that show no significant change between different ethnic groups and different periods of publication; these are the onset of ossification, the time span of partial union, and the appearance of complete union. Despite the relatively long time spans of the maturation stages, bone age estimation based on the study of the development of the medial clavicular epiphysis may be a useful tool in forensic age identification in living individuals, especially if the age of the subject is about the end of the second or the beginning of the third decade of life (e. g. in determining the applicability of adult or juvenile penal systems). Another possible use is in identifying human remains whose age is estimated at under 30 years.

Adolescent↗
PubMed1998

[Acute vascular perforation with shunt formation in the right ventricle after percutaneous transluminal coronary angioplasty. Magnetic resonance tomography and Doppler ultrasound detection of shunt flow].

A coronary artery perforation is a rare complication after percutaneous transluminal coronary angioplasty. The therapy will be determined by the hemodynamic failure of the left or right ventricle. A case of a coronary artery perforation with a shunt from the right coronary artery to the right ventricle after coronary angioplasty is reported. The shunt was detected by coronary angiography and confirmed by magnetic resonance imaging and doppler echocardiography.

Aged↗
PubMed1998

[Histotomography studies of direct radiogenic dental enamel changes].

OBJECTIVE: The volume of literature on radiation-induced caries is still inconsistent as regards the state of the art. Our histotomographic studies have shown direct radiogenic effects on the dentoenamel junction (atrophy of the odontoblast processes). Whether there are direct effects of radiation on dental enamel is not yet known. MATERIAL AND METHOD: Sound teeth (group 1, n = 10) were compared either with enamel specimens after high dose in vitro radiation (500-2500 Gy; group 2; n = 10) and after experimental enoral in situ irradiation (60 Gy; group 3; n = 20), or with teeth from patients after cancer radiotherapy (36 Gy; group 4; n = 20) and with teeth which had obviously decayed due to cancer radiotherapy (60 Gy; group 5; n = 20). Vestibular enamel surfaces of the teeth were exposed to identical in vitro demineralizations (lactic acid gel; pH = 5.0). Each of the samples was prospectively studied histologically by confocal laser scanning microscopy (CLSM) after 90, 180 and 270 min of acid interaction. Data were interpreted micromorphometrically (width of the demineralized area) and micromorphologically. RESULTS: The width of the demineralized area varies between the two in vivo irradiated groups of specimens (group 4: P < 0.01; group 5: P < 0.001) and the high dose in vitro irradiated teeth (P < 0.01) and is significantly different from the sound controls. The histological image of the demineralization in subsurface areas in the teeth of radiotherapy patients is characterized by a total loss of the prismatic structure (homogeneously, amorphous substance). CONCLUSIONS: Direct radiogenic effects at the dentoenamel junction have been described earlier. The additional information offered by this study is that there are significant micromorphometric differences in the demineralizing behaviour of irradiated enamel. Obviously, enamel is less resistant to acid attack after irradiation.

Cobalt Radioisotopes↗
PubMed1998

[Magnetic resonance imaging (MRI) of liver and brain in hematologic-oncologic patients with fever of unknown origin].

PURPOSE: To examine the advantage of liver and brain MRI in clinically anomalous haematological patients with fever of unknown origin. MATERIAL AND METHODS: Twenty liver MRI (T2-TSE, T2-HASTE, T1-FLASH +/- Gd dynamic) and 16 brain MRI (T2-TSE, FLAIR, T1-TSE +/- Gd) were performed searching for a focus of fever with a suspected organ system. Comparison with clinical follow-up. RESULTS: A focus was detected in 11/20 liver MRI. Candidiasis (n = 3), mycobacteriosis (n = 2), relapse of haematological disease (n = 3), graft versus host disease (n = 1), non-clarified (n02). The remaining 9 cases with normal MRI were not suspicious of infectious hepatic disease during follow-up. In brain MRI, 3/16 showed a focus (toxoplasmosis, aspergillosis, mastoiditis). Clinical indication for an infectious involvement of the brain was found in 4/16 cases 2-5 months after initially normal brain MRI. No suspicion of an infectious involvement of brain was present in the remaining 9/16 cases. CONCLUSION: In case of fever of unknown origin and suspicion of liver involvement, MRI of the liver should be performed due to data given in literature and its sensitivity of 100%. Because of the delayed detectability of cerebral manifestations, in cases of persisting suspicion even a previously normal MRI of the brain should be repeated.

Aspergillosis↗
PubMed1998

[Low-field MR arthrography of the shoulder: early results using an open 0.2T MR system].

PURPOSE: To assess the practicability and image quality of doing MR arthrography of the shoulder using a 0.2T system. PATIENTS AND METHOD: 60 patients (24 with chronic instability, 36 with impingement syndrome) were examined in an open 0.2T MR apparatus (Magnetom Open, Siemens). After the intra-articular injections of 15-20 ml of a 2 mmol Gd-DTPA solution, coronary STIR, T1-weighted, sagittal and axial T2*-weighted FLASH 2D sequences were performed. 21 patients subsequently underwent surgery. RESULTS: Image quality of the T1- and T2*-weighted FLASH 2D sequences was regarded as good or adequate and movement artifacts were minor or moderate. STIR sequences were statistically significantly worse in respect of image quality and movement artifacts (p < 0.001, p < 0.005). The sensitivity and specificity in the diagnosis of rotator cuff rupture as confirmed by surgery was 100% (labrum lesions 100%, 93%). Agreement in the diagnosis of rupture of the supraspinatus and infraspinatus tendons was 0.93 and 0.65. CONCLUSION: MR arthrography of the shoulder using an open 0.2 T MR system provides adequate information concerning the intra articular structures of the joint. The disadvantage is the prolonged duration of the examination with the risk of poor image quality resulting from movement artifacts.

Adult↗
PubMed1998

[Effect of oxygen inhalation on hemodynamics in chronic thromboembolic pulmonary hypertension].

PURPOSE: This study evaluates the haemodynamic effects of oxygen inhalation on pulmonary artery pressure and pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension. METHOD: In 47 patients with chronic thromboembolic pulmonary hypertension haemodynamic parameters were measured before and after oxygen inhalation. RESULTS: In moderately severe and severe pulmonary hypertension oxygen inhalation significantly reduced mean pulmonary artery pressure by about 11.1% and 4.6%, respectively. However, pulmonary vascular resistance was not significantly affected. Oxygen saturation improved and heart rate was reduced. Cardiac index decreased in severe pulmonary hypertension. Systemic vascular resistance increased. CONCLUSION: We conclude that oxygen inhalation reduces pulmonary artery pressure and improves oxygen supply in patients with moderately severe and severe chronic thromboembolic pulmonary hypertension.

Blood Pressure↗
PubMed1998

[Chronic thromboembolic pulmonary hypertension: hemodynamic effects of selective pulmonary artery DSA with nonionic contrast media].

PURPOSE: This study evaluates the effects of pulmonary bolus injection of nonionic contrast medium on pulmonary artery pressure and resistance in patients with chronic thromboembolic pulmonary hypertension. METHODS: In 39 patients (age 52 +/- 15) haemodynamic measurements were performed during bolus injection of nonionic contrast medium in a control group (I), in moderately severe (II) and severe pulmonary hypertension (III). RESULTS: Initial inspiratory arrest caused significant pressure increase in all groups prior to bolus injection (delta PAsyst: 7.1 +/- 6.7 [I], 6.8 +/- 3.9 [II] und 7.2 +/- 7.9 mmHg p < 0.05). However, contrast bolus injection (25.1 +/- 2.3 ml iopamidol, 13.0 ml/s) caused only minor additional pressure increase (delta PAsyst: 2.2 +/- 1.4 [I], 2.7 +/- 1.9 [II] und 4.9 +/- 5.4 mmHg [III] p < 0.05). After angiography pulmonary artery pressure and vascular resistance was increased only moderately, predominantly in group III. Systemic vascular resistance was slightly decreased. CONCLUSION: In patients with moderately severe and severe chronic thromboembolic pulmonary hypertension bolus injection of nonionic contrast medium causes no major haemodynamic effects.

Adult↗
PubMed1998

[Flow quantification of intracardiac shunt volumes using MR phase contrast technique in the breath holding phase].

PURPOSE: Comparison of a breath-hold, velocity-encoded, phase-difference magnetic resonance (MR) sequence for intracardiac shunt flow measurement with the invasive shunt size determination by oximetry. PATIENTS AND METHODS: 10 patients with different cardiac shunts (6 ASD/3 VSD/1 PDA) and four healthy individuals were investigated using a 1.5 Tesla Siemens Vision system. For flow measurements a breath-hold, velocity-encoded, phase-difference magnetic resonance (MR) sequence was used ('through plane', FLASH 2D-sequence, TR/TE 110/5 ms, 'velocity encoding' 250 cm/s). Mean flow (ml/R-R interval) in the ascending aorta, the pulmonary trunk, and the right and left pulmonary arteries was determined. The ratio of the mean flow in the pulmonary circulation (Qp: sum of the mean flows in the right and left pulmonary arteries) and the systemic circulation (Qs: mean flow in the proximal aorta) was compared with the Qp/Qs ratios determined by the invasive oxymetric technique. Oximetry was performed within 24 hours after MR imaging. RESULTS: In the 4 healthy individuals MR flow measurement yielded a Qp/Qs ratio of 0.96 +/- 0.15. In the 10 patients with the various shunt defects, the non-invasive shunt determination by MR gave a Qp/Qs ratio of 2.09 +/- 0.67. The percentage of the calculated shunt sizes was 47.05 +/- 17.45%. In the comparison with the results determined by the invasive oxymetric technique, the MR data showed a strong correlation of r = 0.87. CONCLUSIONS: Breath-hold, velocity-encoded, phase-difference MR-technique enables a reliable quantification of cardiac shunts within a short acquisition time.

Adult↗