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Biomedical subjects

A Bauer

Publications and source records attributed to A Bauer.

At least 127 records · Page 7Linked to original sources
PubMed1999

Improved imaging of liver metastases with stimulated acoustic emission in the late phase of enhancement with the US contrast agent SH U 508A: early experience.

PURPOSE: To see whether stimulated acoustic emission (SAE) in the liver parenchyma in the late phase of enhancement with SH U 508A increases the conspicuity of occult metastases at ultrasonography (US). MATERIALS AND METHODS: Eighteen patients with known hypo- or hypervascular hepatic metastases underwent US after SH U 508A administration, after a delay of at least 5 minutes, to ensure decay of blood pool enhancement. In 16 patients with visible metastases, conspicuity was compared on registered SAE and gray-scale scans by two blinded readers and by using computerized analysis of relative gray-scale and color Doppler conspicuity scores inside and outside the lesion. In nine patients, areas suspected of being involved but without definite gray-scale masses were imaged in the same way. Paired sections were analyzed by two blinded readers looking for parenchymal color defects without corresponding gray-scale masses; nine control images from three healthy volunteers were also included. RESULTS: Intense, transient parenchymal SAE was seen in all subjects. All metastases appeared as areas of reduced or absent signal. The conspicuity score was 80% for SAE versus 9% for gray-scale US (P < .001, Wilcoxon signed rank test). SAE-specific defects were seen in all patients but in none of the volunteers. Metastases seen on SAE but undetectable on gray-scale images were proved in three patients. CONCLUSION: SAE with SH U 508A improves the conspicuity of metastases. SAE-specific defects may reveal isoechoic or subtle metastases.

Biopsy↗
PubMed1999

Vulval diseases need an interdisciplinary approach.

BACKGROUND: Vulval diseases are common, but their frequency and importance are often underestimated. OBJECTIVE: The study intended to evaluate the number of patients with vulval diseases seen in medical practice. Furthermore, the acceptance of an interdisciplinary vulval disease clinic, managed by a dermatologist in cooperation with a gynaecologist and a psychologist, was evaluated. METHODS: In April and Mai 1998, a mailing survey of all gynaecologists (n = 239), general practitioners (n = 244) and dermatologists (n = 96) in Thuringia, Germany, containing 7 questions concerning patients with vulval diseases was performed. RESULTS: 49% (n = 286) of the questionnaires were returned. On average, 97% of the physicians regularly treated females with genital diseases. The most common diseases mentioned by all specialities were local fungal and bacterial infections. The further ranking of diagnosis was different between the specialities. It was estimated that 83% of patients with chronic disorders would develop additional psychological problems. The necessity of an interdisciplinary vulval disease clinic in Thuringia was stated by 71% of the interviewed physicians. 76% of the gynaecologists and 75% of the general practitioners welcomed the introduction of the clinic. Interestingly, only 51% of the dermatologists felt that a vulval disease clinic was necessary. CONCLUSION: The majority of the physicians in Thuringia welcomed an interdisciplinary vulval disease clinic to improve the conditions for women suffering from genital diseases.

Dermatology↗
PubMed1999

A novel way to induce erythroid progenitor self renewal: cooperation of c-Kit with the erythropoietin receptor.

Red blood cells are of vital importance for oxygen transport in vertebrates. Thus, their formation during development and homeostasis requires tight control of both progenitor proliferation and terminal red cell differentiation. Self renewal (i.e. long-term proliferation without differentiation) of committed erythroid progenitors has recently been shown to contribute to this regulation. Avian erythroid progenitors expressing the EGF receptor/c-ErbB (SCF/TGFalpha progenitors) can be induced to long-term proliferation by the c-ErbB ligand transforming growth factor alpha and the steroids estradiol and dexamethasone. These progenitors have not yet been described in mammals and their factor requirements are untypical for adult erythroid progenitors. Here we describe a second, distinct type of erythroid progenitor (EpoR progenitors) which can be established from freshly isolated bone marrow and is induced to self renew by ligands relevant for erythropoiesis, i.e. erythropoietin, stem cell factor, the ligand for c-Kit and the glucocorticoid receptor ligand dexamethasone. Limiting dilution cloning indicates that these EpoR progenitors are derived from normal BFU-E/CFU-E. For a detailed study, mEpoR progenitors were generated by retroviral expression of the murine Epo receptor in bone marrow erythroblasts. These progenitors carry out the normal erythroid differentiation program in recombinant differentiation factors only. We show that mEpoR progenitors are more mature than SCF/TGFalpha progenitors and also do no longer respond to transforming growth factor alpha and estradiol. In contrast they are now highly sensitive to low levels of thyroid hormone, facilitating their terminal maturation into erythrocytes.

Animals↗
PubMed1999

Sonographic detection of acute parenchymal injury in an experimental porcine model of renal hemorrhage: gray-scale imaging using a sonographic contrast agent.

OBJECTIVE: The purpose of this study was to determine the usefulness of contrast-enhanced sonography in the detection of acute parenchymal injury. SUBJECTS AND METHODS: In a model of acute renal injury in pigs, four separate renal parenchymal bleeds were created by puncturing an interlobar artery of the upper and lower poles of the kidneys. B-mode gray-scale scans of the kidneys before and after injury, and after the administration of i.v. and intraarterial (i.a.) contrast agents were recorded on videotape for 5 min for each condition (baseline, after injury, after i.v. contrast administration, and after i.a. contrast administration). For each condition and injury, selected frames were analyzed with regions of interest of the normal renal parenchyma, the area of injury, and the perinephric space. Randomized videotape clips from each of the experimental conditions were rated by three sonologists as to the presence or absence of increased intrarenal parenchymal echogenicity, perinephric echogenicity, and confidence as to whether renal injury was present. RESULTS: Areas of renal injury were isoechoic with normal parenchyma on unenhanced scans. After both i.v. and i.a. contrast material injection, areas of injury were visible as areas of increased echogenicity. Contrast increased from 0.2 on unenhanced images to 4.0 and 4.5, respectively, after i.v. and i.a. administration of the new contrast agent. The three observers' ability to diagnose renal injury increased from 0.61, 0.64, and 0.54 to 0.71, 0.70, and 0.74 after i.v. injection and to 0.93, 0.92, and 0.97 after i.a. injection as indicated by the area under the curve in the receiver operating characteristic analysis. CONCLUSION: Transabdominal contrast-enhanced gray-scale sonography can reveal the area of acute renal hemorrhage. This procedure may be applicable in patients when sonographic contrast agents, imaging procedures, and modes of contrast administration are optimized for clinical use in trauma.

Animals↗
PubMed1999

[A cancer mortality atlas on a small geographic scale: procedure, validity and possibilities for its use].

Cancer mortality in two counties (Dithmarschen and Nordfriesland) of the Federal State of Schleswig-Holstein (Germany) was assessed by analysing the death certificates for the period from 1980 to 1991. Age-adjusted cancer mortality rates were calculated for the more common cancers for counties as well as for smaller sub-scales. The procedure in respect of data base, data protection, data flow, calculation of rates and mapping of cancer mortality rates on small geographic scales is described and discussed. The data collected by us was compared with the data provided by the offices of statistic affairs on a county scale (only for the more common cancers). The comparison was done for each gender and each county, respectively. The agreement was high (> 95%) for 16 of 22 compared items, and below 90% for two items only. The validity of the data, therefore, was considered sufficient for epidemiological studies. As an example, results regarding female breast cancer rates are shown. The possibilities for the utilization of cancer registries on small geographic scales are discussed: Depending on the incidence of the occurrence of different cancers, cancer registries should provide data on multiple regional scales. A more flexible use of the possibilities of the assessment of regional cancer rates is imperative to utilise the very expensive and time-consuming instruments of analytical epidemiological studies of the causes of cancer more effectively.

Age Factors↗
PubMed1998

Pontin52, an interaction partner of beta-catenin, binds to the TATA box binding protein.

beta-catenin, the vertebrate homolog of the Drosophila Armadillo protein, has been shown to have dual cellular functions, as a component of both the cadherin-catenin cell adhesion complex and the Wnt signaling pathway. At Wnt signaling, beta-catenin becomes stabilized in the cytoplasm and subsequently available for interaction with transcription factors of the lymphocyte enhancer factor-1/T-cell factor family, resulting in a nuclear localization of beta-catenin. Although beta-catenin does not bind DNA directly, its carboxyl- and amino-terminal regions exhibit a transactivating activity still not well understood molecularly. Here we report the identification of an interaction partner of beta-catenin, a nuclear protein designated Pontin52. Pontin52 binds beta-catenin in the region of Armadillo repeats 2-5 and, more importantly, also binds the TATA box binding protein. We provide evidence for an in vivo multiprotein complex composed of Pontin52, beta-catenin, and lymphocyte enhancer factor-1/T-cell factor. Our results suggest involvement of Pontin52 in the nuclear function of beta-catenin.

Amino Acid Sequence↗
PubMed1998

Insulin-mimetic signalling of synthetic phosphoinositolglycans in isolated rat adipocytes.

A set of synthetic phosphoinositolglycan (PIG) compounds has been demonstrated to exert insulin-mimetic activity on glucose and lipid metabolism in rat adipocytes differing considerably in potency [compound 41>37>45>>7>1; W. Frick, A. Bauer, J. Bauer, S. Wied and G. Müller, G. (1998) Biochemistry 37, 13421-13436]. In the present study we examine whether these differences are based on the capability of the PIG compounds to stimulate signalling components which are thought to mediate metabolic insulin action. Studies using a tyrosine kinase inhibitor and introduction into adipocytes of anti-phosphotyrosine or inhibitory anti-insulin receptor beta-subunit antibodies demonstrated dependence on tyrosine phosphorylation but independence of insulin receptor kinase activation of the insulin-mimetic signalling and metabolic activity of the PIG compounds. The five compounds elicited in rat adipocytes a significant increase in tyrosine phosphorylation of both insulin receptor substrate 1 (IRS-1) and IRS-3 and, to a minor degree, IRS-2, in IRS-1/3-associated phosphatidylinositol 3-kinase (PI 3-K) protein as well as activity, and in protein kinase B (PKB) activity as well as phosphorylation. This was most pronounced for compound 41, approaching 65-95% of the maximal insulin response (MIR) at 20 microM, and declined in the order of compounds 37, 45, 7 and 1. The same ranking was true for the maximal inhibition of glycogen synthase kinase 3 activity (GSK-3) (41, 75% of MIR; compound 37, 65%; compound 7, 25%; compound 1, 10%) and GSK-3 autophosphorylation. The half-maximal concentrations effective for signalling (compound 41, 2-5 microM; compound 37, 10-20 microM) corresponded well to those stimulating glucose and lipid metabolism. Interestingly, compounds 37 and 41 stimulated mitogen-activated protein kinase (MAPK) and protein synthesis in rat adipocytes to only about 20-30% (at 50 microM) of MIR. We conclude that in rat adipocytes: (i) the potency of PIG compounds to regulate glucose/lipid metabolism depends on the activation of PI 3-K and PKB and inhibition of GSK-3; (ii) initiation of tyrosine phosphorylation of IRS-1/3 is sufficient and activation of the PI 3-K cascade is required for insulin-mimetic metabolic signalling; and (iii) PIG compounds are quite selective for the PI 3-K compared to the MAPK cascade, (iv) PIG compounds seem to use the same signalling components downstream of PI 3-K (including Rab4) for stimulation of glucose transport as does insulin. Thus the early signalling step(s) used by PIG, but not by insulin, may represent a target for the treatment of insulin-resistant states.

Adipocytes↗
PubMed1998

Modification of the E-cadherin-catenin complex in mitotic Madin-Darby canine kidney epithelial cells.

One of the hallmarks of polarized epithelial cells undergoing mitosis is their rounded morphology. This phenotype correlates with a reduced cell-substratum adhesion, apparently caused by a modulation of integrin function. However, it is still unclear whether the cadherin-mediated cell-cell adhesion is affected as well. To address this question, the cadherin complex was analyzed in different cell cycle stages of Madin-Darby canine kidney cells. By immunofluorescence, mitotic Madin-Darby canine kidney cells showed an increased staining of E-cadherin and the catenins (alpha-catenin, beta-catenin, plakoglobin, p120(ctn)) in the cytosol, suggesting a reorganization of the cadherin-catenin complex during mitosis. Biochemical analysis revealed that the overall amount of these components, as well as the proportion of the complex associated with the actin cytoskeleton, remained unchanged in mitotic cells. However, we found evidence for an internalization of E-cadherin during mitosis. In addition, the cadherin-catenin complex was analyzed for mitosis-specific changes in phosphorylation. We report a decrease in the tyrosine phosphorylation of beta-catenin, plakoglobin, and p120(ctn) during mitosis. Moreover, we observed a mitosis-specific Ser/Thr-phosphorylation of p120(ctn), as detected by the MPM-2 antibody. Hence, the cadherin/catenin complex is a target for different posttranslational modifications during mitosis, which may also have a profound impact on cadherin-mediated cell-cell adhesion.

Adenomatous Polyposis Coli Protein↗
PubMed1998

Structure-activity relationship of synthetic phosphoinositolglycans mimicking metabolic insulin action.

Phosphoinositolglycan (PIG) molecules have been implicated to stimulate glucose and lipid metabolism in insulin-sensitive cells and tissues in vitro and in vivo. The structural requirements for this partial insulin-mimetic activity remained unclear so far. For establishment of a first structure-activity relationship, a number of PIG compounds were synthesized consisting of the complete or shortened/mutated glycan moiety derived from the structure of the glycosylphosphatidylinositol (GPI) anchor of the GPI-anchored protein, Gce1p, from yeast. The PIG compounds were divided into four classes according to their insulin-mimetic activity in vitro with the typical representatives: compound 41, HO-SO2-O-6Manalpha1(Manalpha1-2)-2Manalpha1 (6-HSO3)- -6Manalpha1-4GluNb eta1-6(D)inositol-1,2-(cyclic)-phosphate; compound 37, HO-PO(H)O-6Manalpha1(Manalpha1-2)-2Manalpha1-6Manal pha1-4GluNbeta1-6( D)inositol-1,2-(cyclic)-phosphate; compound 7, HO-PO(H)O-6Manalpha1-4GluN(1-6(L)inositol-1,2-(cyclic)-ph osp hate; and compound 1, HO-PO(H)O-6Manalpha1-4GluN(1-6(L)inositol. Compounds 41 and 37 stimulated lipogenesis up to 90% (at 20 microM) of the maximal insulin response but with differing concentrations required for 50% activation (EC50 values 2.5 +/- 0.9 vs 4.9 +/- 1.7 microM) as well as glycogen synthase (4.7 +/- 1 vs 9.5 +/- 1.5 microM) and glycerol-3-phosphate acyltransferase (3.5 +/- 0.8 vs 8.0 +/- 1.1 microM). Compound 7 was clearly less potent (20% of the maximal insulin response at 100 microM), whereas compound 1 was almost inactive. This relative ranking in the insulin-mimetic potency between members of the PIG classes (e.g., 41 > 37 >> 7 > 1) was also observed for the (i) activation of glucose transport and glucose transporter isoform 4 translocation in isolated normal and insulin-resistant adipocytes, (ii) inhibition of lipolysis in adipocytes, (iii) stimulation of glucose transport and glycogen synthesis in isolated normal and insulin-resistant diaphragms, and (iv) induction of tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in diaphragms. The complete glycan core structure (Man3-GluN) of typical GPI anchors including a mannose side chain and the inositolphosphate moiety was required for maximal insulin-mimetic activity of the PIG compounds with some variations possible with respect to the type of residues coupled to the terminal mannose/inositol as well as the type of linkages involved. These data argue for the potency and specificity of the interaction of PIG molecules with putative signaling component(s) (presumably at the level of the IRS proteins) in adipose and muscle cells which finally lead to insulin-mimetic metabolic activity even in insulin-resistant states.

Adipocytes↗
PubMed1998

The thyroid hormone receptor functions as a ligand-operated developmental switch between proliferation and differentiation of erythroid progenitors.

The avian erythroblastosis virus (AEV) oncoprotein v-ErbA represents a mutated, oncogenic thyroid hormone receptor alpha (c-ErbA/ TRalpha). v-ErbA cooperates with the stem cell factor-activated, endogenous receptor tyrosine kinase c-Kit to induce self-renewal and to arrest differentiation of primary avian erythroblasts, the AEV transformation target cells. In this cooperation, v-ErbA substitutes for endogenous steroid hormone receptor function required for sustained proliferation of non-transformed erythroid progenitors. In this paper, we propose a novel concept of how v-ErbA transforms erythroblasts. Using culture media strictly depleted from thyroid hormone (T3) and retinoids, the ligands for c-ErbA/TRalpha and its co-receptor RXR, we show that overexpressed, unliganded c-ErbA/ TRalpha closely resembles v-ErbA in its activity on primary erythroblasts. In cooperation with ligand-activated c-Kit, c-ErbA/ TRalpha causes steroid-independent, long-term proliferation and tightly blocks differentiation. Activation of c-ErbA/ TRalpha by physiological T3 levels causes the loss of self-renewal capacity and induces synchronous, terminal differentiation under otherwise identical conditions. This T3-induced switch in erythroid progenitor development is correlated with a decrease of c-ErbA-associated histone deacetylase activity. Our results suggest that the crucial role of the mutations activating v-erbA as an oncogene is to 'freeze' c-ErbA/ TRalpha in its non-liganded, repressive conformation and to facilitate its overexpression.

Animals↗
PubMed1998

[Intracoronary brachytherapy with strontium/yttrium-90. Initial experiences in Germany].

Restenosis after PTCA is still an unresolved problem and occurs in approximately 30% of our patients despite a stent implantation rate of up to 63%. Intracoronary brachytherapy has the potential to counteract the proliferative component of restenosis as well as to prevent shrinking of the coronary artery. Two years ago, we applied for the license to use the Novoste Beta-Cath system. This is the first report of its use in Germany. Attaining the license was complicated by the facts that this device did not yet have CE-certification (MPG section 17), that brachytherapy is not yet an approved method of treatment (StrSchV section 41), the report of the BfS and the approval by an accredited ethical committee. The application becomes even more complicated by the amount demanded by the LfU for insurance: 1 Million DM for each individual patient (AtDeckV section 15). The final local inspection needs to be performed by an expert from the LfAS (StrSchV section 76). Strontium-90 decays into Yttrium-90 with a half-life time of approximately 28 years. Yttrium-90, too, is a pure beta-emitter with a shorter half-life time of approximately 64 hours and a considerably higher electron energy of maximum 2.27 MeV. Yttrium-90 is the therapeutic agent. The radiation source of the Beta-Cath system consists of 12 single, separate cylinders (pellets, seeds) with a total length of 3 cm. The activity of the total train is approximately 1.3 to 1.5 GBq (35 to 40 mCi). For verification of the dose rate provided by the manufacturer, we performed a check using the GafChromic film. The test dose (exactly 2 mm from the center of the long axis of the activity train) was 150 Gy. We obtained the following results for the optical density: reference source: 0.29 +/- 0.01, source C: 0.318 +/- 0.013 and source D: 0.317 +/- 0.028. For a dose rate of e.g. 0.083 Gy/s, the radiation times are 169 s for a dose of 14 Gy (vessel diameter 2.7 to 3.35 mm) or 217 s for 18 Gy (vessel diameter 3.36 to 4.0 mm), respectively. In our cath lab, the following dose rates were measured: at the lead container: 20 microSv/h, surface of the transfer device: 400 microSv/h, surface of the phantom: 20 microSv/h and surface of the bail out box: 100 microSv/h. Because moving the source train to the tip of the catheter takes only approximately 1 s, the exposure to other tissues or organs is negligible. However, inappropriate handling of the device could cause significant radiation of other organs. Therefore, the importance of intensive training cannot be overemphasized. The results of the currently ongoing multicenter trials (Beta-Cath system trial in the USA and the BRIE trial in Europe) are being anxiously awaited and will have a decisive impact on the medical acceptance of intracoronary radiation for prophylaxis and/or therapy of restenosis.

Angioplasty, Balloon, Coronary↗
PubMed1998

[3-dimensional echo-enhanced transcranial Doppler ultrasound diagnosis].

Echo-enhancing agents improve the signal intensity of transcranial Doppler signals, enabling a novel approach of three-dimensional transcranial vascular imaging by Doppler ultrasound. The basic principle, system requirements and early clinical results with a custom built system are described. Transcranial color Doppler imaging was performed through the temporal bone acoustic window. During i.v. administration of the transpulmonary stable, galactose-based echo-enhancer Levovist (Schering) the video output of the ultrasound scanner was digitized and the spatial position of the recorded frames was simultaneously registered using a mechanical position sensor. After automatic segmentation of the color information, the 3D datasets were reconstructed offline using a Unix-based workstation (Silicon Graphics). Visualization was achieved by maximum intensity projection or surface visualization techniques. Administration of Levovist resulted in good enhancement of the vascular Doppler signal intensity, enabling acquisition of a 3D dataset of the complete circle of Willis with an imaging window of approximately 3-5 min for one i.v. injection. The vascularity of tumors could be recorded as a 3D dataset and further analyzed. The power Doppler technique with echoenhancement proved a valuable tool for 3D dataset recording. 3D datasets clearly facilitated the diagnosis of the vascular anatomy and lesion vascularity and provided additional information on localization of feeders, vascular displacement and extent of tumor vascularity.

Blood Flow Velocity↗
PubMed1998

Antiphospholipid antibodies and lipoprotein (a) in women with recurrent fetal loss.

OBJECTIVE: To estimate the occurrence of lupus anticoagulant, both isotypes of anticardiolipins, IgG and IgM, and lipoprotein (a) in women with recurrent fetal loss. METHOD: 43 women with two or more fetal losses were included in this open, prospective study. They were divided into a group of 32 nullipara who have had only miscarriages and a group of 11 women who besides the fetal losses were able to give birth to at least one live newborn. Two control groups were also added: 35 women who were never pregnant and 15 parous who did not have any miscarriage. The presence of lupus anticoagulant was assessed by the Staclot LA clotting test. IgG and IgM isotypes of anticardiolipins and lipoprotein (a) were determined using the immunoenzymatic methods. RESULTS: Lupus anticoagulant was discovered in only one of 23 examined patients. Abnormally high values of IgG isotype of anticardiolipins were found in two subjects of each control group and in two nullipara with miscarriages only. The increased level of IgM isotype was noted in approx. 50% of patients with recurrent fetal loss, but at least one successful delivery and in control subjects who were never pregnant. In contrast, the frequency of the increased level of this antibody was diminished by half in the remaining two groups: women who delivered a live child (children) without any miscarriage and women who had only miscarriages. Elevated levels of lipoprotein (a) were found in approx. 30% of non-pregnant control subjects and in the patients of both groups; the abnormally high concentration of this lipoprotein was encountered in only 13% of women who gave birth to live newborn(s) and did not have any miscarriage. CONCLUSION: Of all four determined variables, only abnormally high values of lipoprotein (a) may have some prognostic significance in women predisposed to the recurrent fetal loss.

Abortion, Habitual↗