Biomedical subjects

M Doser

Publications and source records attributed to M Doser.

At least 19 recordsLinked to original sources

PubMed2006

Evidence for the production of slow antiprotonic hydrogen in vacuum.

We present evidence showing how antiprotonic hydrogen, the quasistable antiproton (p)-proton bound system, has been synthesized following the interaction of antiprotons with the molecular ion H2+ in a nested Penning trap environment. From a careful analysis of the spatial distributions of antiproton annihilation events, evidence is presented for antiprotonic hydrogen production with sub-eV kinetic energies in states around n=70, and with low angular momenta. The slow antiprotonic hydrogen may be studied using laser spectroscopic techniques.

Journal Article↗

PubMed2006

Seeding of human vascular cells onto small diameter polyurethane vascular grafts.

INTRODUCTION: Thrombogenicity of small diameter vascular prostheses might be reduced by complete coverage of the luminal surface with vascular cells. We investigated cell seeding on polyurethane vascular prostheses (PUVP). METHODS: 45 PUVP were divided into three groups of n = 15 each: Group A (diameter 20 mm, gamma-sterilized), Group B (diameter 4 mm, gamma-sterilized), and Group C (diameter 4 mm, ethylene oxid [Eto]-sterilized). Human smooth muscle cells (SMC), fibroblasts (FB), and endothelial cells (EC) were isolated from saphenous vein segments and expanded in culture. PUVPs were pre-seeded with a mixed culture of FBs and SMCs (mean 7.7 +/- 2.3 x 10(6) cells) followed by EC seeding (mean 4.4 +/- 0.9 x 10(6) cells). Seven days after cell seeding, PUVPs were perfused under a pulsatile flow. Flow definitions were as follows: adaption phase: low flow, resulting pressure: 60/30 mm Hg; high flow: resulting pressure: 160/50 mm Hg, lasting for 4 hours in all groups. Three subgroups were defined out of each group, differing in the perfusion strategy: high flow immediately, adaption phase of 15 minutes followed by high flow, and adaption phase of 30 minutes followed by high flow. Specimens were taken after each seeding procedure, prior to and after perfusion, and then examined using a scanning electron microscope (SEM) and immunohistochemical staining procedures. RESULTS: Pre-seeding with the mixed culture revealed a better initial adhesion in Groups A and B compared to group C (76% vs. 41%). In Groups A and B, EC seeding (adhesion 72%) resulted in a confluent EC layer. Immunohistochemical stainings were positive for collagen IV, laminin, CD31, and factor VIII, but negative for eNOS. In Group C, only isolated cells were found after each seeding procedure, which rounded up and vanished during the next days. When perfused with high-flow immediately, Group A and B prostheses revealed small defects (< 10% of the surface) of all cell layers. After perfusion with an adaption phase of 15 minutes only few defects were found within the EC layer with an intact basement membrane. An adaption phase of 30 minutes resulted in a confluent cell layer without significant cell defects. After perfusion, the endothelial cells also stained positive for eNOS. CONCLUSION: Seeding of a mixed culture consisting of FBs and SMC resulted in an excellent EC adhesion and resistance to shear stress. Cell attachment was better on gamma-sterilized PUVPs compared to Eto-sterilization. The cells obviously maintained their ability to adapt to shear stress.

Adaptation, Physiological↗

PubMed2006

[Tissue engineering of peripheral nerves].

BACKGROUND: In spite of considerable progress in microsurgical techniques, the treatment of long distance defects in peripheral nerves remains challenging for the surgeon. Autologous nerve grafting has been the only applicable procedure to overcome such defects in the past. Due to the known disadvantages of this procedure (neuroma formation and sensory deficits at the donor-site, limited availability of donor-material, etc.) and impaired regenerative results, different tubulisation techniques are discussed more frequently as alternatives to the autologous nerve grafts. AIM OF THE STUDY: In this work, the authors summarise their experiences and results with different synthetically developed materials, cellular and acellular tubes and venous conduits for the reconstruction of peripheral nerve defects. MATERIAL AND METHODS: To analyse peripheral nerve regeneration, we utilised a median nerve model in rats. In these studies nerve gaps up to 40 mm were induced. Guiding tubes of various materials (trimethylene carbonate-epsilon-caprolactone, polyethylene, veins, and collagen) were employed. Furthermore, we introduced Schwann cells as cellular elements into some of the trimethylene carbonate-epsilon-caprolactone tubes. The longest postoperative observation period was nine months. RESULTS: The results demonstrated that only in the case of cellular filled tubes (syngenic Schwann cells) did regeneration occur across the 20 mm gap. This regeneration was comparable to that induced after autologous grafting. Across a 40 mm gap the autologous graft demonstrated the best results.

Animals↗

PubMed2005

New source of dense, cryogenic positron plasmas.

We have developed a new method, based on the ballistic transfer of preaccumulated plasmas, to obtain large and dense positron plasmas in a cryogenic environment. The method involves transferring plasmas emanating from a region with a low magnetic field (0.14 T) and relatively high pressure (10(-9) mbar) into a 15 K Penning-Malmberg trap immersed in a 3 T magnetic field with a base pressure better than 10(-13) mbar. The achieved positron accumulation rate in the high field cryogenic trap is more than one and a half orders of magnitude higher than the previous most efficient UHV compatible scheme. Subsequent stacking resulted in a plasma containing more than 1.2 x 10(9) positrons, which is a factor 4 higher than previously reported. Using a rotating wall electric field, plasmas containing about 20 x 10(6) positrons were compressed to a density of 2.6 x 10(10) cm(-3). This is a factor of 6 improvement over earlier measurements.

Journal Article↗

PubMed2005

Direct measurements of Ab and Ac using vertex and kaon charge tags at the SLAC detector.

Exploiting the manipulation of the SLAC Linear Collider electron-beam polarization, we present precise direct measurements of the parity-violation parameters A(c) and A(b) in the Z-boson-c-quark and Z-boson-b-quark coupling. Quark-antiquark discrimination is accomplished via a unique algorithm that takes advantage of the precise SLAC Large Detector charge coupled device vertex detector, employing the net charge of displaced vertices as well as the charge of kaons that emanate from those vertices. From the 1996-1998 sample of 400 000 Z decays, produced with an average beam polarization of 73.4%, we find A(c)=0.673+/-0.029(stat)+/-0.023(syst) and A(b)=0.919+/-0.018(stat)+/-0.017(syst).

Journal Article↗

PubMed2005

Spatial distribution of cold antihydrogen formation.

Antihydrogen is formed when antiprotons are mixed with cold positrons in a nested Penning trap. We present experimental evidence, obtained using our antihydrogen annihilation detector, that the spatial distribution of the emerging antihydrogen atoms is independent of the positron temperature and axially enhanced. This indicates that antihydrogen is formed before the antiprotons are in thermal equilibrium with the positron plasma. This result has important implications for the trapping and spectroscopy of antihydrogen.

Journal Article↗

PubMed2005

A low-flow adaptation phase improves shear-stress resistance of artificially seeded endothelial cells.

INTRODUCTION: The purpose of this study was to evaluate the effect of different adaptation phases on the shear-stress resistance of endothelial cells seeded artificially onto vascular prostheses and biological heart valves. MATERIAL AND METHODS: Human endothelial cells (EC), fibroblasts (FB), and smooth muscle cells (SMC) were isolated from vena saphena magna pieces and expanded in culture. Group A: 15 polyurethane vascular grafts (20 mm diameter) were seeded with FB and SMC (53 +/- 1.2 million cells), followed by EC seeding (39 +/- 0.9 million cells). Group B: eight stentless porcine valves (Freestyle, Medtronic, USA) were seeded with FB (68 +/- 1.5 million cells) and EC (42 +/- 1.1 million cells). Shear-stress testing was done under pulsatile flow (pulse rate: 80 pulses/min.). Adaptation phase: flow was set to 0.9 +/- 0.3 l/min (systolic pressure: 40 - 50 mm Hg). High flow was 3.2 +/- 0.6 l/min. (systolic pressure: 140 - 160 mm Hg) and lasted over four hours in all groups. The vascular grafts were divided into three groups (n = 5 each): group 1 (high flow immediately), group 2 (adaptation phase of 15 minutes), and group 3 (adaptation phase of 30 minutes). The valves either were given high flow immediately (n = 4) or had an adaptation phase of 30 minutes (n = 4). Specimens were obtained after cell seeding, before, and after perfusion. RESULTS: A confluent EC layer was achieved on all grafts. After perfusion without adaptation, large defects within the cell layer were found. No FB and SMC were seen at the bottom of these defects. In group B, the defects were largest on the ventricular surface of the leaflets. After an adaptation phase of 15 minutes in group A, only a few defects within the EC layer were detected with a still confluent FB and SMC. After a 30-minute adaptation phase defects within the EC layer were very rare and no interruption of the underlying FB and SMC layer was seen. Immunohistochemical staining for factor VIII and CD31 proved the EC to be viable and staining for collagen IV and laminin revealed the formation of a basement membrane. After perfusion, the specimen also stained positive for eNOS. CONCLUSION: An adaptation phase of 30 minutes proved to be sufficient to allow artificially seeded endothelial cells to adapt to shear stress. The formation of a basement membrane was of great importance for the maintenance of a confluent EC layer.

Adaptation, Physiological↗

PubMed2005

Encapsulation of islets in rough surface, hydroxymethylated polysulfone capillaries stimulates VEGF release and promotes vascularization after transplantation.

The transplantation of encapsulated islets of Langerhans is one approach to treat type 1 diabetes without the need of lifelong immunosuppression. Capillaries have been used for macroencapsulation because they have a favorable surface-to-volume ratio and because they can be refilled. It is unclear at present whether the outer surface of such capillaries should be smooth to prevent, or rough to promote, cell adhesions. In this study we tested a new capillary made of modified polysulfone (MWCO: 50 kDa) with a rough, open-porous outer surface for islet transplantation. Compared with free-floating islets, encapsulation of freshly isolated rat islets affected neither the kinetics nor the efficiency of glucose-induced insulin release in perifusion experiments. Free-floating islets maintained insulin secretion during cell culture but encapsulated islets gradually lost their glucose responsiveness and released VEGF. This indicated hypoxia in the capillary lumen. Transplantation of encapsulated rat islets into diabetic rats significantly reduced blood glucose concentrations from the first week of implantation. This hypoglycaemic effect persisted until explantation 4 weeks later. Transplantation of encapsulated porcine islets into diabetic rats reduced blood glucose concentrations depending on the islet purity. With semipurified islets a transient reduction of blood glucose concentrations was observed (2, 8, 18, 18 days) whereas with highly purified islets a sustained normoglycaemia was achieved (more than 28 days). Explanted capillaries containing rat islets were covered with blood vessels. Vascularization was also observed on capillaries containing porcine islets that were explanted from normoglycaemic rats. In contrast, on capillaries containing porcine islets that were explanted from hyperglycemic rats a fibrous capsule and lymphocyte accumulations were observed. No vascularization on the surface of transplanted capillaries was observed in the absence of islets. In conclusion, encapsulated islets can release VEGF, which appears to be an important signal for the vascularization of the capillary material. The rough, open-porous outer surface of the polysulfone capillary provides a site well suited for vascular tissue formation and may allow a prolonged islet function after transplantation.

Animals↗

PubMed2004

Three-dimensional annihilation imaging of trapped antiprotons.

We demonstrate three-dimensional imaging of antiprotons in a Penning trap, by reconstructing annihilation vertices from the trajectories of the charged annihilation products. The unique capability of antiparticle imaging has allowed, for the first time, the observation of the spatial distribution of the particle loss in a Penning trap. The radial loss of antiprotons on the trap wall is localized to small spots, strongly breaking the azimuthal symmetry expected for an ideal trap. Our observations have important implications for detection of antihydrogen annihilations.

Journal Article↗

PubMed2003

Positron plasma diagnostics and temperature control for antihydrogen production.

Production of antihydrogen atoms by mixing antiprotons with a cold, confined, positron plasma depends critically on parameters such as the plasma density and temperature. We discuss nondestructive measurements, based on a novel, real-time analysis of excited, low-order plasma modes, that provide comprehensive characterization of the positron plasma in the ATHENA antihydrogen apparatus. The plasma length, radius, density, and total particle number are obtained. Measurement and control of plasma temperature variations, and the application to antihydrogen production experiments are discussed.

Journal Article↗

PubMed2003

Improved direct measurement of the parity-violation parameter Ab using a mass tag and momentum-weighted track charge.

We present an improved direct measurement of the parity-violation parameter A(b) in the Z boson-b-quark coupling using a self-calibrating track-charge technique applied to a sample enriched in Z-->bb events via the topological reconstruction of the B hadron mass. Manipulation of the Stanford Linear Collider electron-beam polarization permits the measurement of A(b) to be made independently of other Z-pole coupling parameters. From the 1996-1998 sample of 400,000 hadronic Z decays, produced with an average beam polarization of 73.4%, we find A(b)=0.906+/-0.022(stat)+/-0.023(syst).

Journal Article↗

PubMed2003

Areal density measurement is a convenient method for the determination of porcine islet equivalents without counting and sizing individual islets.

The determination of islet mass is important for the normalization of islet experiments in the laboratory and for the precise dosing of islets for transplantation. The common microscopical analysis is based on individual islet sizing, calculation of the frequency distribution, and conversion into islet equivalents (IEQ), which is the volume of a spherical islet with a diameter of 150 microm. However, islets are of irregular form, which makes this determination user dependent, and the analysis is irreproducible once the original sample is discarded. This routine technique of islet quantification was compared with the analysis of areal density measurements. It was assumed that the entire area occupied by islets can be expressed in IEQ without sizing and counting individual islets. Porcine islets were isolated by continuous digestion/filtration and purified by gradient centrifugation. Purified islets were stained with dithizone and were repeatedly pictured under the microscope with random area selection. A total of 51 pictures was taken from 11 different purifications and stained islets were detected by digital image analysis. The correlation coefficient (r) between bothanalyses was 0.977 with an underestimation of islet yield by areal density detection (slope: 0.75 +/- 0.03). Areal density analysis per picture took about 1 min, which is about 10 times faster than the traditional method without increasing the method error (CV 2.1% vs. 2.7%). In summary, areal density measurements allow a rapid and reproducible estimation of IEQ without counting individual islets. It can be performed in a single step analysis without computer programming and is valuable for online determinations of islet yield preceding transplantation.

Animals↗

PubMed2002

Production and detection of cold antihydrogen atoms.

A theoretical underpinning of the standard model of fundamental particles and interactions is CPT invariance, which requires that the laws of physics be invariant under the combined discrete operations of charge conjugation, parity and time reversal. Antimatter, the existence of which was predicted by Dirac, can be used to test the CPT theorem-experimental investigations involving comparisons of particles with antiparticles are numerous. Cold atoms and anti-atoms, such as hydrogen and antihydrogen, could form the basis of a new precise test, as CPT invariance implies that they must have the same spectrum. Observations of antihydrogen in small quantities and at high energies have been reported at the European Organization for Nuclear Research (CERN) and at Fermilab, but these experiments were not suited to precision comparison measurements. Here we demonstrate the production of antihydrogen atoms at very low energy by mixing trapped antiprotons and positrons in a cryogenic environment. The neutral anti-atoms have been detected directly when they escape the trap and annihilate, producing a characteristic signature in an imaging particle detector.

Journal Article↗

PubMed2002

Improved direct measurement of A(b) and A(c) at the Z(0) pole using a lepton tag.

The parity violation parameters A(b) and A(c) of the Zb(b) and Zc(c) couplings have been measured directly, using the polar angle dependence of the polarized cross sections at the Z(0) pole. Bottom and charmed hadrons were tagged via their semileptonic decays. Both the electron and muon analyses take advantage of new multivariate techniques to increase the analyzing power. Based on the 1993-1998 SLD sample of 550,000 Z(0) decays produced with highly polarized electron beams, we measure A(b) = 0.919+/-0.030(stat)+/-0.024(syst), and A(c) = 0.583+/-0.055(stat)+/-0.055(syst).

Journal Article↗

PubMed2002

Cultivation of porcine hepatocytes in polyurethane nonwovens as part of a biohybrid liver support system.

Many patients suffering from end-stage liver disease cannot be transplanted within reasonable time due to the shortage of donor organs. Bioartificial liver support systems may contribute to the liver regeneration or bridging the time until a liver graft for transplantation becomes available. Nonwovens with integrated oxygenation capacity have been developed and manufactured by melt blow technology using thermoplastic polyurethane. Capillary membranes for oxygenation were integrated into the nonwoven during the processing. The polyurethane nonwoven structures with adapted pore size and high pore volume allow high cell densities in the hepatocyte culture. The three-dimensional cell culture was housed by a flow bioreactor system and was integrated in a closed loop circulation with monitoring possibilities for pressure, pH, temperature, ammonia, and oxygen. Hepatocytes were isolated from rats or pigs by collagenase perfusion and infused into the medium-perfused circulation. Cells showed high viability and hepatocyte specific cytochrome P450-dependent metabolic function in culture (MEGX test).

Albumins↗

PubMed2001

Improved direct measurement of leptonic coupling asymmetries with polarized Z bosons.

We present final measurements of the Z boson-lepton coupling asymmetry parameters A(e), A(mu), and A(tau) with the complete sample of polarized Z bosons collected by the SLD detector at the SLAC Linear Collider. From the left-right production and decay polar angle asymmetries in leptonic Z decays we measure A(e) = 0.1544+/-0.0060, A(mu) = 0.142+/-0.015, and A(tau) = 0.136+/-0.015. Combined with our left-right asymmetry measured from hadronic decays, we find A(e) = 0.1516+/-0.0021. Assuming lepton universality, we obtain a combined effective weak mixing angle of sin (2)theta(eff)(W) = 0.230 98+/-0.000 26.

Journal Article↗

PubMed2001

First symmetry tests in polarized Z0 decays to bbg.

We have made the first direct symmetry tests in the decays of polarized Z0 bosons into fully identified bbg states, collected in the SLD experiment at SLAC. We searched for evidence of parity violation at the bbg vertex by studying the asymmetries in the b-quark polar- and azimuthal-angle distributions, and for evidence of T-odd, CP-even or CP-odd, final-state interactions by measuring angular correlations between the three-jet plane and the Z0 polarization. We found results consistent with standard model expectations and set 95% C. limits on anomalous contributions.

Journal Article↗

PubMed2001

In vitro test of new biomaterials for the development of a bioartificial pancreas.

The implantation of macroencapsulated islets has the potential to restore endogenous insulin secretion in type 1 diabetics, with no need for lifetime immunosuppression. To match the physiological fluctuations of blood glucose concentrations with appropriate insulin release, the macroencapsulation material must combine immunoprotection with optimal diffusion properties for glucose and insulin. The impact of chemical modifications of polysulphone (PSU) capillary polymers with a cutoff of 50 kD on glucose-induced insulin secretion of macroencapsulated rat islets was studied in perifusion experiments. The insulin release of free-floating islets showed the typical rapid response to glucose stimulation. Total insulin release (AUC between minute 30 and 120 of perifusion) reached 117+/-22 ng/ml. Blending PSU with polyvinylpyrrolidone or sodium-dodecyl-sulfate was not suitable for islet macroencapsulation, since glucose-induced insulin release was absent or disturbed. Hydroxy-methylation (CH2OH) of PSU improved the secretory behavior of macroencapsulated islets depending on the degree of PSU substitution (DS 0.8, AUC 62+/-15 ng/ml; DS 1.8, 111+/-24 ng/ml). In highly substituted PSU-capillaries the kinetics of glucose-induced insulin release was very similar to that observed in free-floating islets. Two consecutive glucose stimulations potentiated insulin release of free-floating islets during the second period of stimulation. Furthermore, freshly isolated macroencapsulated islets responded with more efficient insulin secretion after the initial priming. In conclusion, in vitro membrane screening identified highly substituted hydroxy-methylated PSU as the material of choice for islet encapsulation in a bioartificial pancreas.

Animals↗