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Biomedical subjects

E Fröhlich

Publications and source records attributed to E Fröhlich.

At least 19 recordsLinked to original sources
PubMed2005

[Contrast-enhanced "low MI real-time" sonography for the assessment of the malignancy of focal liver lesions].

PURPOSE: Contrast enhanced sonography using phase-inversion harmonic mode is a promising technique to detect and characterize hepatic lesions. Aim of the following study was to evaluate whether this technique can characterize liver tumors. MATERIAL AND METHODS: During January and December 2004, 46 patients with a solitary liver lesion were examined. The age of the 21 women and 25 men ranged between 37 and 82 years. The tumor size was between 8 mm and 14.5 cm. First conventional B-mode sonography and color-coded sonography were performed, followed by intravenous injection of the contrast agent SonoVue and continuous sonographic examination over 5 minutes using "low MI real-time" phase-inversion mode. The examination was video taped. The enhancement was evaluated qualitatively. RESULTS: Of the 21 malignant lesions, 20 could be correctly diagnosed as malignant. One of the malignant lesions was classified as benign. Of the 25 benign lesions, 21 could be classified correctly as benign, however, 4 lesions (2 hemangiomas, 1 adenoma, 1 teratoma) showed no enhancement in the portal and late phase and were incorrectly classified as malignant as well. CONCLUSION: Using pulse-inversion harmonic US with SonoVue, liver lesions showing an isoechoic or hyperechoic enhancement can be classified as probably benign. Further work up is necessary in case of little or no enhancement on delayed phase imaging.

Adult↗
PubMed2005

Distribution and colocalization of markers for proliferation, invasion, motility and neoangiogenesis in benign melanocytic naevi and malignant melanomas.

BACKGROUND: Melanomas are heterogeneous tumours, and differentiation from other melanocytic lesions may cause problems. It may be possible that the distribution and/or colocalization pattern of different markers in the lesions can enable a more accurate diagnosis of melanocytic tumours. OBJECTIVES: To test this hypothesis, melanocytic naevi, primary melanomas and metastases were investigated. METHODS: The distribution and colocalization of markers for proliferation, invasion, angiogenesis and motility of the tumour cells were investigated using antibodies directed against actin, cathepsin B (CatB), transforming growth factor-beta, vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen/Ki-67 and basic fibroblast growth factor (FGF-2). In addition, melanoma markers (HMB-45 and Melan-A) and proteins unrelated to melanoma progression [epidermal growth factor (EGF) and cathepsin H] were investigated. RESULTS: Malignant melanomas tended to express more markers of malignancy compared with melanocytic naevi, and the differences were statistically significant for EGF and actin immunoreactivity: melanocytic naevi displayed clear EGF labelling more often (60% vs. 5%) and melanomas showed more intense actin labelling (70% vs. 0%). HMB-45+ cells to a large extent also stained with antibodies to CatB but not to EGF or actin; EGF-, FGF-2- and VEGF-immunoreactive cells were predominantly HMB-45-. Similar combinations were observed in melanocytic naevi and in melanomas. CONCLUSIONS: Labelling with EGF may improve the differential diagnosis of melanocytic neoplasias. However, we did not detect a clear-cut increase of markers of malignancy in melanoma. Cells expressing multiple malignancy markers were also found in some melanocytic naevi; this may confirm the dormant potential of melanocytic naevi for melanoma development.

Biomarkers, Tumor↗
PubMed2002

[Structure and function of blood-tissue barriers].

SUMMARY: Pharmacologic effects caused by systemic administration of drugs in some organs are prevented by poor transport of the often large or hydrophilic molecules to the parenchyme. The exclusion of macromolecules from the tissue is called blood-tissue barrier. Common examples for barriers are the blood-brain, the blood-placenta-, the blood-retina-, the blood-testis- and the blood- thymus-barrier. The barriers have a well defined anatomic substrate: for the blood-brain-, the inner blood- retina and the blood-thymus-barrier it is the endothelium, for the blood-placenta-, the outer blood-retina-, the blood-testis- and the blood-thymus-barrier these are epithelial cells in the vicinity of the capillary. Epithelia with barrier-function typically have dense intercellular junctions and few pinocytotic vesicles. They express many transporters for the selective transport and for the exchange of molecules. One group of transporters is responsible for the multi-drug resistance. Inflammations and tumors are the most common causes for disturbances of the blood-tissue-barriers. Strategies available for drug delivery to tissues with barriers include the opening of the barrier and the modification of the drug. The opening of the permeability can be achieved by the co-application of the respective drug with mediators as bradykinin or hyperosmolar concentrations of mannitol. Modifications of the drug include lipidization of the molecule, enclosure into liposomes and coupling to substances that are actively taken up by the cells. The pharmaceutical treatment of organs with blood-tissue barriers requires both an efficacious drug and an special application strategy.

Biological Transport, Active↗
PubMed2002

[Suspected acute coronary syndrome in patients without ST-elevation. Exclusion of infarction, early clinical estimation and non-coronary diagnoses].

BACKGROUND AND OBJECTIVE: Patients admitted to the hospital with suspected acute coronary syndrome (ACS) represent a collective at high risk. The NOWIS substudy aimed at evaluating 3 points: (1) Safe exclusion of myocardial infarction by history, symptoms, biochemical markers and the ECG, (2) value of the first diagnosis by the physician in the emergency room, and (3) prevalence and distribution of non-coronary leading diagnoses. PATIENTS AND METHODS: In 164 patients admitted with suspected ACS without ST-segment elevation (73 % men, median age 66 years) the cardiac markers myoglobin, troponin T and CK/CK-MB were assessed on admission and 4 h later. In 2 of the NOWIS centers, the diagnosis on admission, derived from the ECG, history and clinical symptoms, was compared with the leading diagnosis at discharge, based on coronary angiography and, if negative, on additional esophago-gastroscopy. RESULTS: (1) Myoglobin was the biochemical marker with the highest sensitivity 4 h after admission for acute myocardial infarction (classic) definition by CK-MB elevation) with 90.4 %, followed by troponin T with 84.6 %. Four h after admission, in 15.4 % of the infarction patients (prevalence 31.7 %) troponin T was normal. (2) The admission diagnosis instable angina pectoris was confirmed in 46.7 % (57 of 122), suspected acute infarction in 76.2 % (32 of 42). On the other hand, 90.4 % (57 of 63) of the patients with instable angina as leading diagnosis at discharge were correctly diagnosed on admission, but only 61.5 % (32 of 42) of the patients with infarction. (3) At discharge, 29.9 % (49 of 164) of the patients had a non-coronary leading diagnosis. Here, the most common were gastro-intestinal (55.1 %), costo-vertebral (18.4 %) and broncho-pulmonary (16.3 %). CONCLUSIONS: (1) Troponin and myoglobin are helpful in patients without ST-segment elevation; yet, 4 h after admission, a safe exclusion of myocardial infarction is not possible. (2) The clinical diagnosis on admission is important. However, it corresponds with the leading diagnosis at discharge, based on coronary angiography, in only 50 to 75 %. Patients admitted with suspected ACS should be monitored for 24 h in the hospital (chest pain units or coronary care units). (3) Nearly one third of the patients initially admitted with suspected ACS show a non-coronary leading diagnosis, thus underlining the value of further investigations and of an interdisciplinary approach.

Acute Disease↗
PubMed2001

Activity, expression, and transcription rate of the cathepsins B, D, H, and L in cutaneous malignant melanoma.

BACKGROUND: Increased activity of the protease cathepsin B has been demonstrated in many tumor cells. A correlation of cathepsin B activity and metastatic potential of melanoma has been well established. METHODS: The cathepsins B, D, H, and L were evaluated in normal skin, nevi, and melanoma samples to obtain information about their role and their regulation in melanoma. The authors localized specific proteolytic activity with histochemistry, cathepsin protein immunohistochemistry, and mRNA with in situ hybridization. RESULTS: Activities and immunoreactivities of the cathepsins B and L were found to be increased in all melanocytic lesions. However, the staining for the corresponding mRNA levels was elevated only in melanomas. Cathepsin D protein and mRNA were expressed to a higher degree only in the dysplastic nevus and in melanomas. The increase was due to tumor cells and cells of the surrounding tissue. Cathepsin H activity, immunoreactivity, and mRNA appeared to be correlated inversely with the invasive potential of the lesion. CONCLUSIONS: It may be relevant for the malignant potential of the lesion whether the increase in activity is accompanied by an increase in the mRNA level. Two different mechanisms-the existence of different mRNAs and the higher transcription rate of the cathepsin gene-have been proposed for the regulation of cathepsin B activity in tumor cells. The current data suggest that, depending on the thickness of the melanoma, cathepsin activity is regulated by different mechanisms. The up-regulation of cathepsin gene transcription appears to be characteristic for more invasive tumor cells.

Cathepsins↗
PubMed2001

Enzymatic heterogeneity of bovine retinal pigment epithelial cells in vivo and in vitro.

BACKGROUND: The retinal pigment epithelium (RPE) contains a variety of enzymes that are involved in the metabolism of the neural retina. It has been shown that the photoreceptor densities display regional variations. We aimed to find out whether the enzymes in the RPE also display regional differences. METHODS: Various enzymes were localized in RPE cells in situ and in cultured RPE cells. RPE cells of the entire tapetal region of adult and fetal bovine eyes were examined. The following enzymes were studied: Activities of aminopeptidases A and M, dipeptidylpeptidases I and II, and gamma-glutamyltranspeptidase were localized by histochemistry. Alkaline phosphatase, dipeptidylpeptidase IV, and cathepsin B were studied by histochemistry and immunocytochemistry. In addition, activities of two enzymes were localized in one cell. RESULTS: The distribution pattern of the enzymatic activities showed no marked regional differences. In contrast, pronounced cell-to-cell variability in the activities was detected for some of the enzymes tested. These intercellular differences were detected already in fetal retinae of early stages and persisted in RPE cultures. CONCLUSION: The heterogeneous distribution of enzymatic activities in RPE cells appears not to be caused exclusively by stimuli from the neural retina and from the choroid, because heterogeneity starts in the early fetal period and persists in culture.

Alkaline Phosphatase↗
PubMed2001

Effects of retinoids on porcine thyrocytes under different culture conditions.

The purpose of the paper was to study the morphological effects of retinoids on non-transformed cells such as thyrocytes. The formation of follicles was studied in primary cultures of porcine thyrocytes by adding retinol and thyroid stimulating hormone (TSH) to cells grown in the absence of TSH to form monolayers. The proliferation and apoptosis of thyrocytes were studied in cells both grown adherent to plastic surfaces and in suspension. Standard medium with traces of retinol and the same medium without retinol were used. Retinol alone was added to thyrocytes grown in the absence of TSH (TSH [symbol: see text] culture) or both retinol and TSH were added to cultures after stimulation with TSH (TSH [symbol: see text] culture). The concentration was varied from 0 to 80 microM for retinol and from 0 to 13 microM for retinoic acid. At a concentration of 13 microM, the effect of retinol was similar to that of retinoic acid. At concentrations higher than 40 microM, retinol reduced the formation of thyroglobulin-immunoreactive follicles, whereas up to 13 microM retinoic acid had no obvious influence on follicle formation. The retinoids induced apoptosis under all experimental conditions. In contrast, a significant decrease in proliferation and in the formation of thyroglobulin-immunoreactive follicles was observed only in adherent cells cultured in customary medium. The decrease in functional follicles after treatment with retinol suggests a de-differentiating effect of retinoids on normal thyrocytes and is in contrast with the differentiating effect of retinoids observed in cancer cells.

Animals↗
PubMed2001

The proteasomal substrate Stm1 participates in apoptosis-like cell death in yeast.

We have identified the yeast gene STM1 in an overexpression screen for new proteasomal substrates. Stm1 is unstable in wild-type cells and stabilized in cells with defective proteasomal activity and thus a bona fide substrate of the proteasome. It is localized in the perinuclear region and is required for growth in the presence of mutagens. Overexpression in cells with impaired proteasomal degradation leads to cell death accompanied with cytological markers of apoptosis: loss of plasma membrane asymmetry, chromatin condensation, and DNA cleavage. Cells lacking Stm1 display deficiency in the apoptosis-like cell death process induced by treatment with low concentrations of H(2)O(2). We suggest that Stm1 is involved in the control of the apoptosis-like cell death in yeast. Survival is increased when Stm1 is completely missing from the cells or when inhibition of Stm1 synthesis permits proteasomal degradation to decrease its amount in the cell. Conversely, Stm1 accumulation induces cell death. In addition we identified five other genes whose overexpression in proteasomal mutants caused similar apoptotic phenotypes.

Animals↗
PubMed2001

Diagnosis of symptomatic intestinal metastases using transabdominal sonography and sonographically guided puncture.

OBJECTIVE. We studied the sonographic findings of symptomatic intestinal metastases and the use and safety of subsequent sonographically guided 22-gauge fine-needle aspiration or 18-gauge core biopsy. CONCLUSION. Symptomatic intestinal metastases can be diagnosed by transabdominal sonography. Extensive hypoechoic segmental bowel wall thickening with loss of stratification and intussusception can be observed. Sonographically guided fine-needle aspiration or 18-gauge core biopsy performed at the end of the examination allows definite diagnosis and is a safe procedure.

Aged↗
PubMed2000

Glutamine synthetase and marker enzymes of the blood-retina barrier in fetal bovine retinal pigment epithelial cells.

BACKGROUND: Glutamine synthetase is involved in the recycling of synaptically released glutamate and GABA and in the detoxification of ammonia. It is present in the Müller cells of the neural retina but not in the retinal pigment epithelial (RPE) cells of adult mammals. In human retinal pathological conditions glutamine synthetase has also been detected in RPE cells. In this case glutamine synthetase may provide the cells with glutamine needed for proliferation. Proliferation is also intense during retinal development. METHODS: We studied the distribution of glutamine synthetase immunoreactivity in fetal bovine retinae, especially in the RPE. The maturity of the RPE was demonstrated by histochemical detection of gamma-glutamyltranspeptidase, alkaline phosphatase and Na/K-ATPase as marker enzymes for the blood-retina barrier and by electron microscopy. RESULTS: We found that in the first 3 months of gestation glutamine synthetase immunoreactivity is located exclusively in the RPE. During the 3rd month the marker enzymes of the blood-retina barrier begin to appear. From the 4th month on, RPE cells are glutamine synthetase immunonegative. CONCLUSION: Glutamine in RPE cells in early development may supply glutamine for the intensely proliferating cells in the retina. Glutamine synthetase immunoreactivity in human retinal pathological conditions may indicate reinduction of an enzyme used in earlier development.

Animals↗
PubMed1999

Oxygen stress: a regulator of apoptosis in yeast.

Oxygen radicals are important components of metazoan apoptosis. We have found that apoptosis can be induced in the yeast Saccharomyces cerevisiae by depletion of glutathione or by low external doses of H2O2. Cycloheximide prevents apoptotic death revealing active participation of the cell. Yeast can also be triggered into apoptosis by a mutation in CDC48 or by expression of mammalian bax. In both cases, we show oxygen radicals to accumulate in the cell, whereas radical depletion or hypoxia prevents apoptosis. These results suggest that the generation of oxygen radicals is a key event in the ancestral apoptotic pathway and offer an explanation for the mechanism of bax-induced apoptosis in the absence of any established apoptotic gene in yeast.

Adenosine Triphosphatases↗
PubMed1999

Effects of retinol on follicular porcine thyrocytes in culture.

Retinoids influence proliferation and differentiation in transformed thyroid cell lines. Retinoids are able to damage cells by destabilizing lysosomal membranes and induce apoptosis in certain cell lines. In normal thyrocytes retinol modulates iodine metabolism. At concentrations higher than 50x10(-6) M retinoids are cytotoxic for normal (not transformed) thyroid cells. The mechanism of this cytotoxicity is unknown. We studied the effect of 7-80x10(-6) M retinol on porcine follicular thyrocytes in culture. In order to differentiate between membrane-destabilizing effects and apoptosis we investigated cultures after incubation with retinol by light- and electron-microscopy and by labeling of potential nicks in the DNA helix by terminal deoxynucleotidyltransferase-dUTP mediated DNA nick end labeling. We conclude that the observed cytotoxicity is caused mainly by the induction of apoptosis.

Animals↗
PubMed1999

[Burns following magnetic resonance tomography study].

Skin burns associated with magnetic resonance imaging (MRI) examinations have been published. We describe the case of a 54-year-old patient with third-degree burns after MRI of the abdomen and pelvis on a 1.5 T MR system.

Abdominal Injuries↗
PubMed1999

[Simple volumetry of ischemic cerebral infarction using computerized tomography. Interobserver and method comparison].

PURPOSE: To study the reliability of brain infarct volume assessment with ruler and calculator. METHODS: The brain infarctions of 45 patients were measured using 3 different methods on CT scans: In each section showing the lesion, the largest diameters were measured and multiplied by the slice thickness using the formula for A) an ellipsoid and B) a cylinder. The sectional volumes were summed up to calculate the entire lesion volume. C) Using the ellipsoid formula, the thickness of all sections showing the lesion were added and used as the third diameter which was multiplied with the two largest diameters of the lesion. The lesion volume was also assessed by planimetry on a workstation and served as reference. Using method A, two independent investigators measured 93 brain infarcts of 49 patients to assess the 95% confidence interval (CI) of agreement. RESULTS: Compared to the reference, method A underestimated the volumes by -25%, method B overestimated the volumes by +12.5%, and method C by +18.6%. The mean difference between the two investigators was 2 ml. The 95% CI for small infarcts < or = 50 ml was 60%-150%, for larger infarcts +/- 26 ml. CONCLUSION: This simple method is only reliable when changes in infarct volume exceeding 26 ml are to be detected.

Brain↗