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Biomedical subjects

E Müller

Publications and source records attributed to E Müller.

At least 37 records · Page 2Linked to original sources

Diamond-like carbon coatings with Ca-O-incorporation for improved biological acceptance.

Diamond-like carbon (DLC) coatings were modified by doping the thin films with Ca-O compounds. Raman spectroscopy indicates growth of sp(2)-hybridised, ordered regions in size and/or number within the amorphous carbon-hydrogen network as a result of the Ca-O-incorporation. CaCO(3) was identified by X-ray induced photoelectron spectroscopy. Proliferation and morphology of L929 mouse fibroblasts reveal improved biocompatibility of Ca-O-modified DLC.

Animals↗

Investigation of interfacial interaction between uncoated and coated carbon fibres and the magnesium alloy AZ91.

Unidirectionally reinforced metal-matrix composites with a fibre volume content between 63 and 68% were processed by squeeze casting using T800 H carbon fibres and the magnesium alloy AZ91. The surface of the fibres was prepared by thermal desizing of the fibres or by deposition of a pyrolytic carbon (pyC) coating. Different interfacial conditions could be identified by transmission electron microscopy (TEM) and the single-fibre push-in test. TEM confirmed the formation of needle-like phases at the fibre surface or, for coated fibres, within the pyrolytic carbon coating. During loading by the Vickers type indenter an intense response was observed for composites of coated fibres and the magnesium alloy. This could by caused by stick-slip effects within the pyrolytic carbon coating.

Journal Article↗

Nasal CPAP therapy: effects of different CPAP levels on pressure transmission into the trachea and pulmonary oxygen transfer.

BACKGROUND: Nasal continuous positive airway pressure (nCPAP) is considered useful for prophylaxis and treatment of respiratory complications following major thoracic surgery. It is unknown, however, which CPAP levels are required to avoid alveolar derecruitment and to consistently improve pulmonary oxygen transfer in patients following thoracotomy. We therefore studied the effects of different nCPAP levels on pressure transmission into the trachea as well as on pulmonary oxygen transfer. METHODS: In 10 consecutive patients after cardiac or thoracic vascular surgery, following extubation in the ICU, nCPAP was generated by means of a high-flow gas source and applied randomly at levels of 5 or 10 cm H2O. Airway pressure was recorded continuously in the nasal mask and the trachea. The PaO2/FiO2ratio was calculated from the tracheal oxygen concentration, and PaO2 was determined while breathing at an ambient and elevated airway pressure. Haemodynamic variables (heart rate, arterial blood pressure, central venous pressure) were also recorded. RESULTS: Mean pressures in the nasal mask were 5.4+/-0.1 and 9.7+/-0.3 cm H2O. Corresponding tracheal pressures were 2.8+/-1.0 vs. 7.2+/-1.1 cm H2O (P=0.007). With higher mask pressure, the fraction of pressure transferred from the nasal mask into the trachea was larger (0.75+/-0.03 vs. 0.52+/-0.05; P=0.04), and tracheal pressures remained positive during the entire respiratory cycle in all patients. In contrast, with 5.4 cm H20, negative pressure changes during inspiration occurred in five out of 10 patients. The PaO2/FiO2 ratio increased from 183+/-53 (ambient pressure) to 199+/-74 (nCPAP 5.4 cm H2O; P=0.25) and to 333+/-54 (nCPAP 9.7 cm H2O; P=0.003). Nasal CPAP did not alter hemodynamics. CONCLUSION: Nasal CPAP is an effective non-invasive means of increasing tracheal and thus intrathoracic pressure without adverse hemodynamic effects. Only mask pressures of 9-10 cm H2O were sufficient to consistently improve pulmonary oxygen transfer in patients following thoracotomy.

Aged↗

Indications of associations of the porcine FOS proto-oncogene with skeletal muscle fibre traits.

Skeletal muscle fibre characteristics are key determinants of meat quality. High fibre diameters and shifting towards higher white fibre proportions lead to increasing R-values (degree of desamination of adenosine) and lactate-production, resulting in high incidences of pale, soft, exudative (PSE) meat and stress susceptibility in European and American pig breeds. Development of muscle fibres including their enzymes, is regulated by the MyoD-gene family together with transcription factors like FOS. We report on the associations between the chromosomal region of FOS with skeletal muscle fibre and metabolism traits. The BB genotype representing the European Pietrain breed had 10.9% more white fibres with fibre diameters decreased by 6.1%, with 3.9% higher R-values and 8.5% higher lactate levels than the AA genotype of the Chinese Meishan. Lactate levels and R-values per microm of fibre diameter were increased to 18.4 and 11.6% in the BB genotype. The contrast between the two quantitative trait loci (QTL) alleles associated with a polymorphism in the FOS gene explained up to 5.13% of the total variance. A new TaiI-restriction fragment length polymorphism (RFLP) connected to a Asn258/Ser mutation, located in a transcription activator region, was used to map FOS between markers S0115 and Sw581 on SSC7. The QTLs for skeletal muscle fibre and metabolism traits have been mapped to the marker interval around FOS. The present data suggest that variability in FOS gene may underlie phenotypic variation in skeletal muscle fibre and metabolism traits in the pig.

Alleles↗

[Calcium-oxygen modified amorphous and nanocrystalline carbon layers as biomaterials].

Undoped and Ca-O-modified diamond-like carbon coatings were deposited by a direct current discharge. Hardness and Young's modulus of Ca-O-modified DLCs were reduced in comparison with the undoped DLC, but the adherence of the Ca-O-modified films is improved. Ca-O-modified DLCs have a higher fraction of nano-crystalline regions with carbon in sp2 hybridisation. In addition, an increased oxygen content and CaCO3 was identified in Ca-O-modified DLCs. While mouse fibroblasts of the type L929 attach and grow on unmodified diamond-like carbon coatings synthesized by the decomposition of hydrocarbon, the addition of CaO-H2O into the precursor gas improves the coatings biological acceptance by the cells.

Animals↗

Nano- and microstructure of short fibre reinforced and unreinforced hydroxyaptite.

Hydroxyapatite (HA) and alumina short fibre reinforced hydroxyapatite (Al2O3/HA) were processed by uniaxial pressing of green bodies with 200 MPa and sintering in air for 4 hours at 1150 degrees C, 1175 degrees C and 1200 degrees C. The phase composition of the materials were investigated by transmission electron microscopy and Raman spectroscopy. Results were supported by X-ray diffraction. Amorphous calcium phosphate could be found either as islands in unreinforced HA or at the grain boundaries in the Al2O3/HA composite. The reinforced calcium phosphate contains an enhanced amount of decomposition products like tetracalcium phosphate.

Aluminum Oxide↗

[Quality assurance of powders for bioceramic applications with image analysis].

Bone substitute materials are very demanding with respect to their quality, in particular, a high toughness and durability are required. In case of producing the composites by sintering of mechanically generated powder mixtures, a high efficiency of mixture is demanded, too. The characterisation of such particle systems is difficult. An effective method is the image analysis supported by statistical evaluation of both the size and the shape distributions of particles and agglomerates. As it is proved by first results, powder mixtures of hydroxyapatite can be described by the geometry of voids in the agglomerate structure using the shape factor weighted by area of the respective image object. As a measure of the efficiency of mixture, the degree of reproducibility was introduced.

Bone Substitutes↗

Community structure of micro- and macroflocs in pin-point sludge and the influence of sludge age and potassium addition on microfloc formation.

Settling problems caused by pin-point sludge constitute a serious problem in biological wastewater treatment, particularly in many industrial plants. Until now, most studies focused on the relationship between pin-point sludge formation and either shearing forces or the impact of toxicants. This study deals with the community structure in both the micro- and macrofloc fraction which was analyzed by fluorescent in situ hybridization (FISH) and BIOLOG substrate utilization patterns. It was shown that each fraction consisted of different microbial communities with unique metabolic profiles suggesting that pin-point sludge formation is not due to dispersal of intact flocs but to microcolonies growing separately. Alternatively, macroflocs may have an architecture leading to segregation of microbial communities after floc dispersal. Further it could be shown that the formation of microflocs was influenced by sludge age. The best sludge sedimentation was obtained for a sludge age of 5 and 10 days. Additional analysis of extracellular polymeric substances (EPS) suggested that the lower protein to carbohydrate ratio of 10-day-old sludge led to better flocculation compared to 20-day-old sludge containing similar total amounts of EPS. From a practical point of view, addition of potassium (0.1 g/l) effected a noticeable improvement of sludge settleability.

Bacteria↗

[Time-related expression of adhesive proteins and other markers of age of injuries].

UNLABELLED: In addition to evidence of the vital reaction it is important from the forensic aspect to assess the age of wounds, in particular in wounds with a short time of survival. To both can contribute detection of adhesive molecules, identified in recent years, possibly in combination with other markers of early stages of reparative inflammation. The submitted paper comprises the results of investigation of 465 skin wounds. The investigated samples were obtained from necroptic material, excision from wounds of treated patients and from experimental injuries in mice. Assessment of the age of injuries by means of endothelial adhesive molecules was made in paraffin sections after transfer into Varioclave and using the ABC techniqueref.. In human material a strong positive reaction of ICAM-1 was observed first after 1 and a half hours and latest after 3 and a half days, in P-selectin first after 3 mins., latest after 7 hours, in E-selectin first after 1 hour and latest after 17 days, in VCAM-1 first after 3 hours and latest 3 and a half days after the development of the injury. Expression of L-selectin was not typical for the injury. In skin injuries of mice positive immunohistochemical reactions were found as a rule sooner than in skin injuries of humans. Fibronectin was detected in paraffin sections from 70 skin wounds of dissected subjects immunohistochemically by the indirect immunoperoxidase reaction and by the use of the ABC technique labelled with alkaline phosphatase. Positive evidence was observed first after 5 minutes and latest after 8 hours. CONCLUSION: Detection of a rise of expression of ICAM-1, VCAM-1 and P- and E. selectin and the formation of basic netlike fibronectin structures improves the assessment of the age of wounds with a short survival period.

Animals↗

New alleles and mutational events in D12S391 and D8S1132: sequence data from an eastern German population.

To investigate the DNA mutation rate and pattern in the hypervariable short tandem repeat (STR) locus D12S391 and in the locus D8S1132, samples from an eastern German population (Dresden area) were analysed. A duplex PCR was applied, using short amplification products for D12S391 (129-177bp) and a modified reverse primer for D8S1132 (127-182bp). The sequences of some rare and new variant alleles are described. At the locus D12S391, 13 regular and six incomplete alleles with different lengths were found, exhibiting several sequence structures. Two isolated father/child mismatches were observed in a total of 648 meioses. Novel alleles 13.1, 14.1 and 27 were discovered at the locus D8S1132. Three parent/child mismatches were found in a total of 672 meioses.

Adult↗

A highly selective telomerase inhibitor limiting human cancer cell proliferation.

Telomerase, the ribonucleoprotein enzyme maintaining the telomeres of eukaryotic chromosomes, is active in most human cancers and in germline cells but, with few exceptions, not in normal human somatic tissues. Telomere maintenance is essential to the replicative potential of malignant cells and the inhibition of telomerase can lead to telomere shortening and cessation of unrestrained proliferation. We describe novel chemical compounds which selectively inhibit telomerase in vitro and in vivo. Treatment of cancer cells with these inhibitors leads to progressive telomere shortening, with no acute cytotoxicity, but a proliferation arrest after a characteristic lag period with hallmarks of senescence, including morphological, mitotic and chromosomal aberrations and altered patterns of gene expression. Telomerase inhibition and telomere shortening also result in a marked reduction of the tumorigenic potential of drug-treated tumour cells in a mouse xenograft model. This model was also used to demonstrate in vivo efficacy with no adverse side effects and uncomplicated oral administration of the inhibitor. These findings indicate that potent and selective, non-nucleosidic telomerase inhibitors can be designed as novel cancer treatment modalities.

Cell Division↗

A central role for the armadillo protein plakoglobin in the autoimmune disease pemphigus vulgaris.

In pemphigus vulgaris (PV), autoantibody binding to desmoglein (Dsg) 3 induces loss of intercellular adhesion in skin and mucous membranes. Two hypotheses are currently favored to explain the underlying molecular mechanisms: (a) disruption of adhesion through steric hindrance, and (b) interference of desmosomal cadherin-bound antibody with intracellular events, which we speculated to involve plakoglobin. To investigate the second hypothesis we established keratinocyte cultures from plakoglobin knockout (PG-/-) embryos and PG+/+ control mice. Although both cell types exhibited desmosomal cadherin-mediated adhesion during calcium-induced differentiation and bound PV immunoglobin (IgG) at their cell surface, only PG+/+ keratinocytes responded with keratin retraction and loss of adhesion. When full-length plakoglobin was reintroduced into PG-/- cells, responsiveness to PV IgG was restored. Moreover, in these cells like in PG+/+ keratinocytes, PV IgG binding severely affected the linear distribution of plakoglobin at the plasma membrane. Taken together, the establishment of an in vitro model using PG+/+ and PG-/- keratinocytes allowed us (a) to exclude the steric hindrance only hypothesis, and (b) to demonstrate for the first time that plakoglobin plays a central role in PV, a finding that will provide a novel direction for investigations of the molecular mechanisms leading to PV, and on the function of plakoglobin in differentiating keratinocytes.

Animals↗

Cofactor requirements for nuclear export of Rev response element (RRE)- and constitutive transport element (CTE)-containing retroviral RNAs. An unexpected role for actin.

Nuclear export of proteins containing leucine-rich nuclear export signals (NESs) is mediated by the export receptor CRM1/exportin1. However, additional protein factors interacting with leucine-rich NESs have been described. Here, we investigate human immunodeficiency virus type 1 (HIV-1) Rev-mediated nuclear export and Mason-Pfizer monkey virus (MPMV) constitutive transport element (CTE)-mediated nuclear export in microinjected Xenopus laevis oocytes. We show that eukaryotic initiation factor 5A (eIF-5A) is essential for Rev and Rev-mediated viral RNA export, but not for nuclear export of CTE RNA. In vitro binding studies demonstrate that eIF-5A is required for efficient interaction of Rev-NES with CRM1/exportin1 and that eIF-5A interacts with the nucleoporins CAN/nup214, nup153, nup98, and nup62. Quite unexpectedly, nuclear actin was also identified as an eIF-5A binding protein. We show that actin is associated with the nucleoplasmic filaments of nuclear pore complexes and is critically involved in export processes. Finally, actin- and energy-dependent nuclear export of HIV-1 Rev is reconstituted by using a novel in vitro egg extract system. In summary, our data provide evidence that actin plays an important functional role in nuclear export not only of retroviral RNAs but also of host proteins such as protein kinase inhibitor (PKI).

Actins↗

CD30-mediated cell cycle arrest associated with induced expression of p21(CIP1/WAF1) in the anaplastic large cell lymphoma cell line Karpas 299.

One of the major characteristics of anaplastic large cell lymphomas (ALCL) is the expression of the Ki-1/CD30 antigen. While the receptor mediates NF-kappaB-activation in Hodgkin's lymphomas, some data suggest the CD30-mediated apoptosis of other CD30-expressing cells. We were able to demonstrate that activation of CD30 leads to different effects regarding cell proliferation of the ALCL-derived cell lines Karpas 299 and JB6. Western and Northern blotting analysis revealed that CD30-induced growth inhibition of Karpas 299 cells correlated with a strong upregulation of the cell cycle inhibitor p21(CIP1/WAF1). We found a non activating point mutation at codon 273 in exon 8 of the p53 gene in Karpas 299 cells which indicates an p53-independent mechanism for induced p21 expression. Abundant p21 protein expression resulted in hypophosphorylation of the retinoblastoma protein (Rb) and inhibition of the proliferating cell nuclear antigen (PCNA). CD30-stimulated cells showed no indications of apoptotic cell death, like genomic DNA fragmentation or cleavage of the caspase-3 target protein poly (ADP-ribose) polymerase (PARP). Our results indicate that CD30 is able to mediate an p21-associated cell cycle arrest in ALCL with possible implications for prognosis and clinical treatment.

Antibodies↗

Regulation of phosphotransferase activity of hexokinase 2 from Saccharomyces cerevisiae by modification at serine-14.

Isoenzyme 2 of hexokinase functions in sugar sensing and glucose repression in Saccharomyces cerevisiae. The degree of in vivo phosphorylation of hexokinase 2 at serine-14 is inversely related to the extracellular glucose concentration [Vojtek, A. B., and Fraenkel, D. G. (1990) Eur. J. Biochem. 190, 371-375]; however, a physiological role of the modification causing the dissociation of the dimeric enzyme in vitro [as effected by a serine-glutamate exchange at position 14; Behlke et al. (1998) Biochemistry 37, 11989-11995] is unclear. This paper describes a comparative stopped-flow kinetic and sedimentation equilibrium analysis performed with native unphosphorylated hexokinase 2 and a permanently pseudophosphorylated glutamate-14 mutant enzyme to determine the functional consequences of phosphorylation-induced enzyme dissociation. The use of a dye-linked hexokinase assay monitoring proton generation allowed the investigation of the kinetics of glucose phosphorylation over a wide range of enzyme concentrations. The kinetic data indicated that monomeric hexokinase represents the high-affinity form of isoenzyme 2 for both glycolytic substrates. Inhibition of glucose phosphorylation by ATP [Moreno et al. (1986) Eur. J. Biochem. 161, 565-569] was only observed at a low enzyme concentration, whereas no inhibition was detected at the high concentration of hexokinase 2 presumed to occur in the cell. Pseudophosphorylation by glutamate substitution for serine-14 increased substrate affinity at high enzyme concentration and stimulated the autophosphorylation of isoenzyme 2. The possible role of hexokinase 2 in vivo phosphorylation at serine-14 in glucose signaling is discussed.

Amino Acid Substitution↗

Possible complication regarding phosphorus removal with a continuous flow biofilm system: diffusion limitation.

Diffusion limitation of phosphate possibly constitutes a serious problem regarding the use of a biofilm reactor for enhanced biological phosphorus removal. A lab-scale reactor for simultaneous removal of phosphorus and nitrate was operated in a continuous alternating mode of operation. For a steady-state operation with excess amounts of carbon source (acetate) during the anaerobic phase, the same amount of phosphate was released during the anaerobic phase as was taken up during the anoxic phase. The measured phosphorus content of the biomass that detached during backwash after an anoxic phase was low, 2.4 +/- 0.4% (equal to 24 +/- 4 mg P/g TS). A simplified computer model indicated the reason to be phosphate diffusion limitation and the model revealed a delicate balance between the obtainable phosphorus contents of the biomass and operating parameters, such as backwash interval, biofilm thickness after backwash, and phase lengths. The aspect of diffusion is considered of crucial importance when evaluating the performance of a biofilter for phosphate removal.

Anaerobiosis↗

[Life threatening complication after transthoracic esophageal resection].

Acute inflow stasis of the vena cava superior is an emergency case. Because of the rapidly rising venous pressure, life-threatening complications can arise (e.g. cerebral hemorrhage, hemorrhagic venous infarcts). The main cause of central venous thrombosis is bronchial carcinoma (incidence: 3-5%). Iatrogenic reasons are thrombosis caused by pacemaker electrodes, dialysis catheter, central vein catheters, implanted ports and radiation-induced venous fibrosis. In this case a patient with an esophageal carcinoma was pretreated by a neoadjuvant chemoradiotherapy. The chemotherapy was given through a venous access port, which was implanted earlier. Radiation therapy with a total of 60 Gy followed. After the esophagectomy the patient developed an acute inflow stasis of the vena cava superior.

Angioplasty, Balloon↗