PubMed Health⌕ Search

Biomedical subjects

C Bauer

Publications and source records attributed to C Bauer.

At least 73 records · Page 4Linked to original sources
PubMed2001

HIF-1 is expressed in normoxic tissue and displays an organ-specific regulation under systemic hypoxia.

Adaptation to hypoxia is regulated by hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor consisting of an oxygen-regulated alpha subunit and a constitutively expressed beta subunit. Although HIF-1 is regulated mainly by oxygen tension through the oxygen-dependent degradation of its alpha subunit, in vitro it can also be modulated by cytokines, hormones and genetic alterations. To investigate HIF-1 activation in vivo, we determined the spatial and temporal distribution of HIF-1 in healthy mice subjected to varying fractions of inspiratory oxygen. Immunohistochemical examination of brain, kidney, liver, heart, and skeletal muscle revealed that HIF-1alpha is present in mice kept under normoxic conditions and is further increased in response to systemic hypoxia. Moreover, immunoblot analysis showed that the kinetics of HIF-1alpha expression varies among different organs. In liver and kidney, HIF-1alpha reaches maximal levels after 1 h and gradually decreases to baseline levels after 4 h of continuous hypoxia. In the brain, however, HIF-1alpha is maximally expressed after 5 h and declines to basal levels by 12 h. Whereas HIF-1beta is constitutively expressed in brain and kidney nuclear extracts, its hepatic expression increases concomitantly with HIF-1alpha. Overall, HIF-1alpha expression in normoxic mice suggests that HIF-1 has an important role in tissue homeostasis.

Animals↗
PubMed2001

Effects of endothelin receptor antagonists on the progression of diabetic nephropathy.

BACKGROUND: Diabetic nephropathy is the leading cause of end-stage renal disease in European countries and is associated with an enhanced renal synthesis of endothelin (ET)-1. ETs are - beside their potent vasoconstrictor properties - very potent profibrotic acting paracrine hormones especially in the kidney. METHODS: We analyzed in rats with streptozotocin-induced diabetes the effects of an ETA-type (ETA) receptor antagonist (LU 135252) in comparison to a combined ETA/ETB receptor antagonist (LU 224332) on the expression of interstitial and glomerular collagen type I, III and IV as well as on fibronectin and laminin by quantitative immunohistochemistry using a computer-aided image analysis system. Global glomerular matrix deposition was analyzed after PAS staining. In addition to the morphometric examination of the kidneys, we also investigated GFR, urinary albumin and total protein excretion. The diabetic rats were treated for 36 weeks. RESULTS: Treatment with either LU 135252 or LU 224332 normalized the amount of PAS-positive material within the glomeruli. The expression of glomerular fibronectin and type IV collagen was increased 36 weeks after induction of diabetes. The overexpression of these two matrix proteins within the glomeruli of diabetic rats was completely abolished by both ET receptor antagonists, whereas protein excretion was only reduced by about 50% as compared to diabetic rats without treatment. CONCLUSION: The present study indicates that ETA receptor antagonists as well as combined ETA/ETB receptor antagonists reduce proteinuria and completely normalize the renal matrix protein expression in hyperglycemic rats with streptozotocin-induced diabetes. The antifibrotic effect seems to be mediated via the ETA receptor. ET receptor antagonists might be a new approach in the treatment of diabetic nephropathy.

Animals↗
PubMed2001

Rescuing desmoplakin function in extra-embryonic ectoderm reveals the importance of this protein in embryonic heart, neuroepithelium, skin and vasculature.

Desmosomes mediate intercellular adhesion through desmosomal cadherins, which interface with plakoglobin (PG) and desmoplakin (DP) to associate with the intermediate filament (IF) cytoskeleton. Desmosomes first assemble in the E3.5 mouse trophectoderm, concomitant with establishment of epithelial polarity and appearance of a blastocoel cavity. Increasing in size and number, desmosomes continue their prominence in extra-embryonic tissues, but as development proceeds, they also become abundant in a number of embryonic tissues, including heart muscle, epidermis and neuroepithelium. Previously, we explored the functional importance of desmosomes by ablating the Dsp gene. Homozygous Dsp mutant embryos progressed through implantation, but did not survive beyond E6.5, owing to a loss or instability of desmosomes and tissue integrity. We have now rescued the extra-embryonic tissues by aggregation of tetraploid (wild-type) and diploid (Dsp mutant) morulae. These animals survive several days longer, but die shortly after gastrulation, with major defects in the heart muscle, neuroepithelium and skin epithelium, all of which possess desmosomes, as well as the microvasculature, which does not. Interestingly, although wild-type endothelial cells of capillaries do not form desmosomes, they possess unusual intercellular junctions composed of DP, PG and VE-cadherin. The severity in phenotype and the breadth of defects in the Dsp mutant embryo is greater than PG mutant embryos, substantiating redundancy between PG and other armadillo proteins (e.g. beta-catenin). The timing of lethality is similar to that of the VE-cadherin null embryo, suggesting that a participating cause of death may be a defect in vasculature, not reported for PG null embryos.

Animals↗
PubMed2001

Bronchial blocker compared to double-lumen tube for one-lung ventilation during thoracoscopy.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) requires one-lung ventilation with a properly collapsed lung. This study compared the Broncho-Cath double-lumen endotracheal tube with the Wiruthan bronchial blocker to determine the advantages of one device over the other during anaesthesia with one-lung ventilation for thoracoscopy. METHODS: Thirty-five patients undergoing VATS were randomly assigned to one of two groups. Sixteen patients received a left-sided double-lumen tube (DLT) and nineteen a Wiruthan bronchial blocker (BB). The BB group was subdivided in two: BB in the right mainstem bronchus (BBR) for right-sided VATS (9 patients), BB in the left mainstem bronchus (BBL) for left-sided VATS (10 patients). The position of the devices was checked using a fibreoptic bronchoscope. The following variables were measured: 1) number of unsuccessful placement attempts; 2) number of malpositions of the devices; 3) time required to place the device in the correct position; 4) number of secondary dislodgements of the devices after turning the patient into the lateral decubitus position. The quality of lung deflation was evaluated by the surgeons who were blinded to the type of tube being used. RESULTS: The number of unsuccessful placement attempts was one in the DLT group (1/16), three in the BBL group (3/10) and none in the BBR group (0/9). The number of malpositions was significantly greater in the BBL group (10/10) compared to the DLT group (2/16) and to the BBR group (1/9) (P<0.001). The time (mean+/-SD) required to place a BBL was 4.21 min+/-1.28, significantly longer than the time required to place a DLT (2.26 min+/-0.55, P<0.0006) or a BBR (2.41 min+/-0.53, P<0.008). The difference in placement time between DLT and BBR was not significant. The number of secondary dislodgements was one in the DLT group, one in the BBR group and none in the BBL group (NS). The quality of lung deflation was judged excellent or fair in all patients in the DLT and the BBL groups and poor in 44% of the patients in the BBR group. CONCLUSION: It took significantly longer to place a left BB than a DLT (P<0.0006) or a right BB (P<0.008). The number of initial malpositionings of the left BB was significantly greater than in the other groups (P<0.001). The quality of lung deflation was better in the BBL and in the DLT groups than in the BBR group. We conclude that for routine use during left-sided VATS, the use of a DLT is preferable to a left BB because of its greater ease of placement. For right-sided VATS, DLT and right BB showed the same facility of placement but the DLT provided a better quality of lung deflation.

Adult↗
PubMed2001

Multispecific resistance of trichostrongyles to benzimidazoles in a goat herd in Germany.

Anthelmintic resistance of nematodes to benzimidazoles and ivermectin was suspected from field observations in an Angora goat herd in northern Hesse. Larvae of the caprine trichostrongyle isolate were used for artificial infections of helminth-naive sheep. Groups of the lambs were treated with albendazole (3.8 mg/kg p.o.) or ivermectin (0.2 mg/kg s.c.) four weeks after infection or remained untreated as controls and were necropsied one week later. Albendazole reduced the mean faecal egg counts by 82% and the mean worm counts of Haemonchus contortus by 22%, Ostertagia circumcincta by 10% and Trichostrongylus colubriformis by 41% as compared with the controls. Ivermectin was 100% effective. This is the first report from Germany of multispecific resistance to benzimidazoles in a trichostrongyle population of goats.

Animals↗
PubMed2000

Determination of polycyclic aromatic hydrocarbons in waste water by off-line coupling of solid-phase microextraction with column liquid chromatography.

A new method for the determination of polycyclic aromatic hydrocarbons (PAHs) in waste water using solvent-free solid-phase microextraction (SPME) is described. The PAHs are extracted with a 100 microm polydimethylsiloxane (PDMS) fiber, desorbed in 40 microl acetonitrile and measured with LC and fluorescence detection. The detection limits of this very simple method under the given conditions (extraction from 5 ml sample, extraction time 1 h) are in the range of 1-6 ng l(-1). The standard deviations (n = 6) at a concentration level of 0.8 microg l(-1) are between 1.8 and 14.4%. The procedure was used for the determination of PAHs in contaminated water samples.

Chromatography, Liquid↗
PubMed2000

Nitric oxide prevents cardiovascular disease and determines survival in polyglobulic mice overexpressing erythropoietin.

Nitric oxide (NO) induces vasodilatatory, antiaggregatory, and antiproliferative effects in vitro. To delineate potential beneficial effects of NO in preventing vascular disease in vivo, we generated transgenic mice overexpressing human erythropoietin. These animals induce polyglobulia known to be associated with a high incidence of vascular disease. Despite hematocrit levels of 80%, adult transgenic mice did not develop hypertension or thromboembolism. Endothelial NO synthase levels, NO-mediated endothelium-dependent relaxation and circulating and vascular tissue NO levels were markedly increased. Administration of the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) led to vasoconstriction of peripheral resistance vessels, hypertension, and death of transgenic mice, whereas wild-type siblings developed hypertension but did not show increased mortality. L-NAME-treated polyglobulic mice revealed acute left ventricular dilatation and vascular engorgement associated with pulmonary congestion and hemorrhage. In conclusion, we here unequivocally demonstrate that endothelial NO maintains normotension, prevents cardiovascular dysfunction, and critically determines survival in vivo under conditions of increased hematocrit.

Animals↗
PubMed2000

Conditional ablation of beta1 integrin in skin. Severe defects in epidermal proliferation, basement membrane formation, and hair follicle invagination.

The major epidermal integrins are alpha3beta1 and hemidesmosome-specific alpha6beta4; both share laminin 5 as ligand. Keratinocyte culture studies implicate both integrins in adhesion, proliferation, and stem cell maintenance and suggest unique roles for alphabeta1 integrins in migration and terminal differentiation. In mice, however, whereas ablation of alpha6 or beta4 results in loss of hemidesmosomes, epidermal polarity, and basement membrane (BM) attachment, ablation of alpha3 only generates microblistering due to localized internal shearing of BM. Using conditional knockout technology to ablate beta1 in skin epithelium, we have uncovered biological roles for alphabeta1 integrins not predicted from either the alpha3 knockout or from in vitro studies. In contrast to alpha3 null mice, beta1 mutant mice exhibit severe skin blistering and hair defects, accompanied by massive failure of BM assembly/organization, hemidesmosome instability, and a failure of hair follicle keratinocytes to remodel BM and invaginate into the dermis. Although epidermal proliferation is impaired, a spatial and temporal program of terminal differentiation is executed. These results indicate that beta1's minor partners in skin are important, and together, alphabeta1 integrins are required not only for extracellular matrix assembly but also for BM formation. This, in turn, is required for hemidesmosome stability, epidermal proliferation, and hair follicle morphogenesis. However, beta1 downregulation does not provide the trigger to terminally differentiate.

Animals↗
PubMed2000

Epolones induce erythropoietin expression via hypoxia-inducible factor-1 alpha activation.

Induction of erythropoietin (Epo) expression under hypoxic conditions is mediated by the heterodimeric hypoxia-inducible factor (HIF)-1. Following binding to the 3' hypoxia-response element (HRE) of the Epo gene, HIF-1 markedly enhances Epo transcription. To facilitate the search for HIF-1 (ant)agonists, a hypoxia-reporter cell line (termed HRCHO5) was constructed containing a stably integrated luciferase gene under the control of triplicated heterologous HREs. Among various agents tested, we identified a class of substances called epolones, which induced HRE-dependent reporter gene activity in HRCHO5 cells. Epolones are fungal products known to induce Epo expression in hepatoma cells. We found that epolones (optimal concentration 4-8 micromol/L) potently induce HIF-1 alpha protein accumulation and nuclear translocation as well as HIF-1 DNA binding and reporter gene transactivation. Interestingly, the activity of a compound related to the fungal epolones, ciclopirox olamine (CPX), was blocked after addition of ferrous iron. This suggests that CPX might interfere with the putative heme oxygen sensor, as has been proposed for the iron chelator deferoxamine mesylate (DFX). However, about 10-fold higher concentrations of DFX (50-100 micromol/L) than CPX were required to maximally induce reporter gene activity in HRCHO5 cells. Moreover, structural, functional, and spectrophotometric data imply a chelator:iron stoichiometry of 1:1 for DFX but 3:1 for CPX. Because the iron concentration in the cell culture medium was determined to be 16 micromol/L, DFX but not CPX function can be explained by complete chelation of medium iron. These results suggest that the lipophilic epolones might induce HIF-1 alpha by intracellular iron chelation. (Blood. 2000;96:1558-1565)

Animals↗
PubMed2000

Directed actin polymerization is the driving force for epithelial cell-cell adhesion.

We have found that epithelial cells engage in a process of cadherin-mediated intercellular adhesion that utilizes calcium and actin polymerization in unexpected ways. Calcium stimulates filopodia, which penetrate and embed into neighboring cells. E-cadherin complexes cluster at filopodia tips, generating a two-rowed zipper of embedded puncta. Opposing cell surfaces are clamped by desmosomes, while vinculin, zyxin, VASP, and Mena are recruited to adhesion zippers by a mechanism that requires alpha-catenin. Actin reorganizes and polymerizes to merge puncta into a single row and seal cell borders. In keratinocytes either null for alpha-catenin or blocked in VASP/Mena function, filopodia embed, but actin reorganization/polymerization is prevented, and membranes cannot seal. Taken together, a dynamic mechanism for intercellular adhesion is unveiled involving calcium-activated filopodia penetration and VASP/Mena-dependent actin reorganization/polymerization.

Actins↗
PubMed2000

Magic-angle sample spinning electron paramagnetic resonance--instrumentation, performance, and limitations.

An electron paramagnetic resonance (EPR) setup for line narrowing experiments with fast sample spinning at variable angles between the rotation axis and the static magnetic field is described and applied in the magic-angle sample spinning (MAS) EPR experiment at X-band frequencies (9.5 GHz). Sample spinning speeds up to 17 kHz at temperatures down to 200 K can be achieved with rotors of 4-mm outer and 2.5-mm inner diameter without severe losses in microwave amplitude compared to standard pulse EPR probeheads. A phase cycle is introduced that provides pure absorption MAS EPR spectra and allows one to distinguish between positive and negative frequency offsets (pseudo-quadrature detection). Possible broadening mechanisms in MAS EPR spectra are discussed. It is demonstrated both by theory and by experiment that the MAS EPR experiment requires excitation bandwidths that are comparable to the total spectral width, since otherwise destructive interference between contributions of spins with similar resonance offsets suppresses the signal. Experimental observations on the E(1) center in gamma-irradiated silica glass and on the SO(-)(3) radical in gamma-irradiated sulfamic acid are reported.

Electron Spin Resonance Spectroscopy↗
PubMed2000

[Standardized morphology-adjusted resection in treatment of benign nodular struma].

In 1996 we performed a prospective study with 279 patients suffering from benign nodular goiter. The study investigates the influence of a standardized morphologically adjusted resection technique--SMART--on complication rates in surgery. Apart from the number of transient and permanent recurrent laryngeal nerve lesions and hypocalcemia, we focused in particular on the rate of "false relapses" associated with residual nodular tissue after resection. Bilateral ligation of the inferior thyroid artery in a bilobal approach as well as the entire preparation towards the ligament of Berry permit a reduction in irreversible nerve lesions in all lobal resections to 0.4% and permanent hypocalcemia to 0.3%. Bilateral ligation of the inferior thyroid artery results in a significantly larger number of transient hypocalcemia, without any impact on the long-term course. By applying a standardized surgical technique, a residual nodular goiter rate of 1.4% can be achieved. In spite of thorough intraoperative exploration, false relapses cannot completely be ruled out, however. Nodular tissue might remain undetected by conventional intraoperative exploration even in the presence of sophisticated preoperative ultrasound of the thyroid gland. Also, performing an enucleation can lead to remaining nodules, particularly in the posterior areas. For the future intraoperative ultrasound may be an interesting method in these doubtful cases.

Diagnosis, Differential↗
PubMed2000

Chronic toxicity of nonylphenol and ethinylestradiol: haematological and histopathological effects in juvenile Common carp (Cyprinus carpio).

In recent ecotoxicological research, there is an increasing concern about alkylphenolic industrial chemicals, such as nonylphenol (NP), because of their estrogenic properties. Data on the general fish toxicity of these wide spread aquatic pollutants are scarce. In order to evaluate sublethal toxic effects of environmentally relevant concentrations of NP, juvenile Common carp (Cyprinus carpio) were exposed to NP concentrations ranging from 1 to 15 microg NP/l over a 70-day period. Classical toxicological endpoints, such as various haematological parameters and histopathological alterations were investigated. In a comprehensive protocol, besides NP-induced effects also alterations due to a treatment with the synthetic estrogen ethinylestradiol (EE2) were evaluated. After both the NP-exposure as well as the EE2-treatment, the predominant haematological finding was a severe anaemia. Histopathological alterations in the kidney, the liver and the spleen occurred exclusively after treatment with EE2, whereas NP-exposed fish did not show any tissue lesions. Depending on the haematological parameter examined, a NOEC between 1 and 5 microg NP/l could be established. From the present findings, it is assumed, that under field conditions, the NP-induced, general toxic effects, might outbalance the relatively weak estrogenic effects of this compound and possibly might disturb ecologically relevant processes such as fish reproduction.

Animals↗
PubMed2000

Prandial glucose regulation with repaglinide: its clinical and lifestyle impact in a large cohort of patients with Type 2 diabetes.

OBJECTIVE: Prandial glucose regulation has the potential for achieving good metabolic control with a low risk of hypoglycaemia and increased flexibility with regard to eating patterns. Comparative studies have suggested that the prandial glucose regulator repaglinide is at least equivalent to sulphonylureas in terms of efficacy, but incurs a lower risk of major hypoglycaemia. However, these trials employed fixed dosing and mealtime regimens, so repaglinide was not used as intended. This prospective investigation in a daily clinical setting aimed to assess the efficacy and tolerability profile of flexible prandial glucose regulation with repaglinide in Type 2 diabetes. DESIGN: 5,985 patients with Type 2 diabetes in Germany were surveyed prospectively. These patients were assessed before and after a mean of 46 days treatment with repaglinide. At baseline, available data showed that 64% of patients had previously received therapy with conventional oral antidiabetic drugs, 22% were on diet alone, and 13% were naive to any treatment. RESULTS: Overall, mean HbA1c decreased from 8.6 to 7.4%, fasting blood glucose from 183.9 to 134.2 mg/dl (10.2 to 7.4 mmol/l), blood glucose prior to main meals from 198.5 to 141.4 mg/dl (11 to 7.8 mmol/l), and blood glucose 2 hours after main meals from 219.3 mg/dl to 153.2 mg/dl (12.2 to 8.5 mmol/l). Subgroup analysis showed significant improvements in each of these parameters (P<0.0001) in therapy-naive patients, in patients switched from other oral antidiabetic drugs, and in patients receiving repaglinide as combination therapy. Body weight decreased slightly (1.2+/-2.7 kg). Only 49 hypoglycaemic episodes were reported, of which 38 cases were mild and no adverse sequelae to these events have been reported. Repaglinide also led to a liberating effect on lifestyle when patients were switched from other oral hypoglycaemic agents (OHAs), with 80% reporting a sense of relief at the prospect of being able to miss meals. The proportion of these patients reporting lifestyle restrictions as a result of fixed mealtimes declined from 36% to 7%. Before switching, 38% of the patients admitted to eating when not hungry for fear of hypoglycaemia, but only 10% continued this behaviour and patients took fewer supplementary snacks after switching to repaglinide. CONCLUSION: Prandial glucose regulation with repaglinide improves metabolic control in patients with Type 2 diabetes without causing weight gain and with few hypoglycaemic episodes. This beneficial effect is seen in patients who are therapy-naive, have switched from alternative OHAs, or are in need of combination therapy. The prandial approach to treatment has a liberating effect with regard to eating behaviour that is welcomed by most patients switched from alternative therapies.

Attitude to Health↗