Search PubMed⌕ Search

Biomedical subjects

U Heinzmann

Publications and source records attributed to U Heinzmann.

At least 19 recordsLinked to original sources
PubMed2002

Time-resolved atomic inner-shell spectroscopy.

The characteristic time constants of the relaxation dynamics of core-excited atoms have hitherto been inferred from the linewidths of electronic transitions measured by continuous-wave extreme ultraviolet or X-ray spectroscopy. Here we demonstrate that a laser-based sampling system, consisting of a few-femtosecond visible light pulse and a synchronized sub-femtosecond soft X-ray pulse, allows us to trace these dynamics directly in the time domain with attosecond resolution. We have measured a lifetime of 7.9(-0.9)(+1.0) fs of M-shell vacancies of krypton in such a pump-probe experiment.

Journal Article↗
PubMed2002

Experimental verification of quadrupole-dipole interference in spin-resolved photoionization.

We have measured the spin polarization of Xe (4p)(-1) photoelectrons after ionization with circularly polarized light at photon energies close to the ionization threshold where a resonant enhancement of quadrupole transitions has recently been predicted. At a reaction angle of 90 degrees a nonvanishing longitudinal spin polarization component of about 4% clearly indicates a quadrupole contribution to the photoexcitation. This is the first experimental evidence for the influence of nondipole transitions on the photoionization process at excitation energies much below 1 keV in an observable other than the intensity angular distribution.

Journal Article↗
PubMed2002

Steering attosecond electron wave packets with light.

Photoelectrons excited by extreme ultraviolet or x-ray photons in the presence of a strong laser field generally suffer a spread of their energies due to the absorption and emission of laser photons. We demonstrate that if the emitted electron wave packet is temporally confined to a small fraction of the oscillation period of the interacting light wave, its energy spectrum can be up- or downshifted by many times the laser photon energy without substantial broadening. The light wave can accelerate or decelerate the electron's drift velocity, i.e., steer the electron wave packet like a classical particle. This capability strictly relies on a sub-femtosecond duration of the ionizing x-ray pulse and on its timing to the phase of the light wave with a similar accuracy, offering a simple and potentially single-shot diagnostic tool for attosecond pump-probe spectroscopy.

Journal Article↗
PubMed2002

Enhanced values of the RBE and H ratio for cytogenetic effects induced by secondary electrons from an X-irradiated gold gurface.

The low-energy secondary electrons emerging from the entrance surface of an X-irradiated gold foil increase the dose to cells in contact with or at micrometer distances from this surface (Radiat. Res. 150, 92-100, 1998). We examined the effect of the spectrum of these low-energy electrons on the RBE for cytogenetic effects and showed that this RBE was increased. A monolayer of surface-attached human T lymphocytes was exposed to 60 kV X rays in the absence or presence of a gold foil positioned immediately behind the cell layer or separated from it by a Mylar foil 0.9 or 2 microm thick. The enhancement of dose in the cell nuclei caused by the photoelectrons and Auger electrons emerging from the entrance surface of the gold foil was measured by TSEE dosimetry. Dose enhancement factors of 55.7, 46.6 and 37.5 were obtained with 0, 0.9 and 2 microm of Mylar inserted between the gold surface and the cell layer. This large enhancement results from the photoelectric effect in the gold foil, as shown by the accompanying Monte Carlo calculations of the secondary electron spectra at the gold surface. Auger electrons from the gold foil generally were not able to penetrate into the cell nuclei except for that fraction of the cells that had a very thin (< 0.7 microm) layer of cytoplasm and membranes between gold surface and cell nucleus. The dose-yield curves for dicentric chromosomes plus centric rings and for acentric fragments obtained after exposures without or with the gold foil were linear-quadratic. The coefficient alpha, the slope of the linear yield component, was increased in the presence of the gold foil and showed RBE values ranging from 1.7 to 2.2 compared to exposures in absence of the gold foil. The ratio of the yield of interstitial deletions and dicentrics (H ratio) was significantly increased from about 0.17 in the absence of the gold foil to about 0.22 in the presence of the gold foil. The increases in the RBE and the H ratio are interpreted in microdosimetric terms: The preferred occurrence of electron track ends in the vicinity of the gold surface causes an increase in the dose-mean restricted linear energy transfer in cell nuclei exposed to the photoelectrons and Auger electrons.

Chromosome Aberrations↗
PubMed2001

Attosecond metrology.

The generation of ultrashort pulses is a key to exploring the dynamic behaviour of matter on ever-shorter timescales. Recent developments have pushed the duration of laser pulses close to its natural limit-the wave cycle, which lasts somewhat longer than one femtosecond (1 fs = 10-15 s) in the visible spectral range. Time-resolved measurements with these pulses are able to trace dynamics of molecular structure, but fail to capture electronic processes occurring on an attosecond (1 as = 10-18 s) timescale. Here we trace electronic dynamics with a time resolution of </= 150 as by using a subfemtosecond soft-X-ray pulse and a few-cycle visible light pulse. Our measurement indicates an attosecond response of the atomic system, a soft-X-ray pulse duration of 650 +/- 150 as and an attosecond synchronism of the soft-X-ray pulse with the light field. The demonstrated experimental tools and techniques open the door to attosecond spectroscopy of bound electrons.

Journal Article↗
PubMed2001

Asymmetry in photoelectron emission from chiral molecules induced by circularly polarized light.

In photoionization of free, unoriented chiral molecules with circularly polarized radiation, a significant circular dichroism, i.e., an asymmetry in the forward-backward electron emission, has been observed in the photoelectron angular distribution. This leads also to an asymmetry in the momentum transfer to the photoions. The spectra for the left- and right-handed enantiomers of bromocamphor exhibit asymmetries up to several percent which vary as a function of orbital binding energy. This enantioselective effect can similarly occur for biomolecules with handedness, like amino acids, and may thus be a contributing factor related to the origin of the terrestrial biomolecular homochirality.

Journal Article↗
PubMed2001

Ischemically compromised myocardium displays different time-courses of functional recovery: correlation with morphological alterations?

OBJECTIVE: It has been demonstrated that positron emission tomography (PET) predicts the functional recovery of viable but ischemically compromised myocardium. Reversible contractile dysfunction after revascularization has been reported for 'hibernating myocardium' and stunned myocardium, however, there are little data concerning the time-course and the extent of improvement of the two different pathophysiological conditions. METHODS: Twenty-nine patients with advanced coronary artery disease and severely reduced left ventricular function (EF 18--35%) who were referred for isolated coronary artery bypass grafting underwent preoperative PET viability assessment and were functionally assessed by two-dimensional echocardiography preoperatively at 11 days, 14 weeks, and more than 12 months after surgical revascularization. Intraoperative biopsies were taken from dysfunctional areas defined by PET as segments of normal perfusion and normal metabolism (stunned myocardium) and from areas with a 'mismatch' between perfusion and metabolism (hibernating myocardium). The degree of morphological alterations was evaluated by electron microscopy. RESULTS: In 70% of the 240 dysfunctional segments, 'stunned myocardium' was present whereas 'hibernating myocardium' could be detected in only 24% (P < 0.01). Hibernating myocardium was associated with more severe preoperative wall motion abnormalities and incomplete postoperative recovery. After 1 year, 31% of 'stunned' segments vs. only 18% of 'hibernating' segments showed complete functional restoration (P < 0.05). This incomplete improvement was associated with more severe morphological alterations including depletion of sarcomeres, accumulation of glycogen, loss of sarcoplasmatic reticulum, and cellular sequestration. CONCLUSIONS: These data indicate that in patients with severe ischemic left ventricular dysfunction 'stunned myocardium' is more prevalent than 'hibernation'. Functional normalization is more frequent in 'stunned' segments, whereas areas of 'hibernation' showed more severe tissue injury and protracted recovery. Different degrees of myocardial injury coexist in most patients, which determines the time-course and the extent of improvement after revascularization.

Aged↗
PubMed2001

Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats.

The cardiovascular system is currently considered a target for particulate matter, especially for ultrafine particles. In addition to autonomic or cytokine mediated effects, the direct interaction of inhaled materials with the target tissue must be examined to understand the underlying mechanisms. In the first approach, pulmonary and systemic distribution of inhaled ultrafine elemental silver (EAg) particles was investigated on the basis of morphology and inductively coupled plasma mass spectrometry (ICP-MS) analysis. Rats were exposed for 6 hr at a concentration of 133 microg EAg m(3) (3 x 10(6) cm(3), 15 nm modal diameter) and were sacrificed on days 0, 1, 4, and 7. ICP-MS analysis showed that 1.7 microg Ag was found in the lungs immediately after the end of exposure. Amounts of Ag in the lungs decreased rapidly with time, and by day 7 only 4% of the initial burden remained. In the blood, significant amounts of Ag were detected on day 0 and thereafter decreased rapidly. In the liver, kidney, spleen, brain, and heart, low concentrations of Ag were observed. Nasal cavities, especially the posterior portion, and lung-associated lymph nodes showed relatively high concentrations of Ag. For comparison, rats received by intratracheal instillation either 150 microL aqueous solution of 7 microg silver nitrate (AgNO(3) (4.4 microg Ag) or 150 microL aqueous suspension of 50 microg agglomerated ultrafine EAg particles. A portion of the agglomerates remained undissolved in the alveolar macrophages and in the septum for at least 7 days. In contrast, rapid clearance of instilled water-soluble AgNO(3) from the lung was observed. These findings show that although instilled agglomerates of ultrafine EAg particles were retained in the lung, Ag was rapidly cleared from the lung after inhalation of ultrafine EAg particles, as well as after instillation of AgNO(3), and entered systemic pathways.

Administration, Inhalation↗
PubMed2000

Sudden interchannel interaction in the Tl 6p ionization above the 5d threshold

The linear magnetic dichroism in the angular distribution of Tl 5d and 6p photoelectrons and their dynamical spin polarization have been measured between hnu = 30 and 50 eV. In contrast to the Xe 5p photoionization at the 4d threshold, our results show that above the Tl 5d threshold strong interchannel coupling effects induce a sudden increase in the asymptotic phase difference of the s and d waves for the Tl 6p ionization. This shows that the valence excitation is different for resonant (Xe 4d) and nonresonant (Tl 5d) excitation from subvalence shells.

Journal Article↗
PubMed2000

Dissolution of copper-rich granules in hepatic lysosomes by D-penicillamine prevents the development of fulminant hepatitis in Long-Evans cinnamon rats.

BACKGROUND/AIM: The Long-Evans cinnamon rat has a mutation homologous to the human Wilson disease gene, leading to gross copper accumulation and the development of hepatitis. D-penicillamine, a copper-chelating drug widely and efficiently used in treating Wilson disease, has also been shown to prevent hepatitis in Long-Evans cinnamon rats. The objectives of this study were: i) to investigate the effectiveness of D-penicillamine when administered to the already affected animals, and ii) to elucidate the mechanism of action of the drug. METHODS: Long-Evans cinnamon rats were divided into groups according to age and treatment with D-penicillamine. The drug was administered orally before and after the onset of hepatitis. Livers were examined by light and electron microscopy. The effect of D-penicillamine on the subcellular distribution and binding of copper was investigated in more detail. Finally, the interaction between D-penicillamine and specific hepatic copper-binding proteins was studied in vitro. RESULTS: D-penicillamine when given to either healthy or diseased animals prevented or reversed hepatitis, respectively. The drug particularly inhibited the disease-specific accumulation of copper in lysosomes of hepatocytes, tissue macrophages and Kupffer cells. When administered to diseased animals, the drug sequestered copper particularly from insoluble lysosomal particles. According to results obtained in vitro, the mobilization of this copper is likely to proceed through the solubilization of these particles. In contrast and as supported by the in vitro data, D-penicillamine had only a minor effect on copper bound to metallothionein in the cytosol. CONCLUSION: Our findings on the Long-Evans cinnamon rat provide some conclusions on the mechanism of action of D-penicillamine in Wilson disease therapy. The drug prevents the formation or promotes the solubilization of copper-rich particles which occur in lysosomes of hepatocytes and Kupffer cells in the livers of patients with Wilson disease. Once chelated with D-penicillamine copper might then be excreted into urine. However, the mobilization of copper by D-penicillamine seems to be limited due to the binding of the metal to metallothionein in liver cytosol. This copper, even at relatively high concentrations, apparently may be well tolerated.

Animals↗
PubMed1998

Loss of the differentiated phenotype precedes apoptosis of ROS 17/2.8 osteoblast-like cells.

Osteoblast cells, recruited from mesenchymal precursors, initiate the final phase of bone remodeling by secreting the protein components of the bone matrix. Upon completion of remodeling, some of these osteoblasts may further differentiate, giving rise to matrix-embedded osteocytes and bone lining cells. The fate of the remaining osteoblasts is unknown, although by analogy with other cell systems, apoptotic cell death may be involved. We induced and characterized the apoptotic process in ROS 17/2.8 osteosarcoma cells by growing and maintaining confluent cultures in low serum medium. At confluence, but prior to apoptosis, the levels of collagen type I, alkaline phosphatase, and osteocalcin mRNAs declined abruptly. Expression of two housekeeping genes (ribosomal protein RPS6 and GAPDH) remained unchanged. Some 72 hours later cells began to show morphological and biochemical features of apoptosis, namely, chromatin condensation, membrane budding, and internucleosomal degradation of genomic DNA. We conclude that serum starvation-induced apoptosis of ROS 17/2.8 cells can serve as a model for investigating the mechanisms of osteoblastic apoptosis.

Animals↗
PubMed1998

Association of copper to metallothionein in hepatic lysosomes of Long-Evans cinnamon (LEC) rats during the development of hepatitis [se e comments].

BACKGROUND: The Long-Evans cinnamon (LEC) rat has a mutation homologous to the human Wilson's disease gene, leading to copper-induced hepatotoxicity. The mechanism of how excess copper damages the liver or what chemical form of copper is toxic is still unclear. RESULTS: In liver cytosol, copper levels were highest just before the onset of hepatitis and declined thereafter. In cytosol, total copper was bound to metallothionein (MT). Considerable amounts of both copper and iron accumulated in lysosomes with increasing age and development of liver damage. Lysosomal levels of presumably reactive non-MT-bound copper were increased. In severely affected livers, large amounts of copper were associated with insoluble material of high density which, upon ultrastructural information, was found to be derived from the lysosomes of Kupffer cells. This copper-rich material is considered to consist of polymeric degradation products of copper-MT. CONCLUSION: We suggest that chronic copper toxicity in LEC rats involves the uptake of copper-loaded MT into lysosomes, where it is incompletely degraded and polymerizes to an insoluble material containing reactive copper. This copper, together with iron, initiates lysosomal lipid peroxidation, leading to hepatocyte necrosis. Subsequent to phagocytosis by Kupffer cells, the reactive copper may amplify liver damage either directly or through stimulation of these cells.

Animals↗
PubMed1996

Analysis of chromosome aberrations in human peripheral lymphocytes induced by in vitro alpha-particle irradiation.

Irradiation of human lymphocytes by alpha-particles under different conditions has been seen to be substantially more effective in the induction of dicentric chromosomes than irradiation by gamma-rays. However, the relative biological effectiveness (RBE) determined in these studies differed by a factor of more than 10. These variations in RBE are likely to be due in part to differing exposure conditions. Therefore, a technique designed to insure uniformity of irradiation was developed in the present study, and complications due to the cell cycle kinetics were controlled. After stimulation with phytohaemagglutinin (PHA), separated lymphocytes were allowed to attach for 3 h to the thin foil bottom of an irradiation chamber. Cell monolayers were exposed with alpha-particles from Am. Strong over-dispersion was noted for the cell-to-cell variance of the number of dicentrics. The dose response of dicentrics was linear, with a yield of 0.27 dicentrics per cell and per Gy. This corresponds to a low dose RBE of 15 relative to Cs gamma-ray exposure under the same experimental conditions.

Alpha Particles↗
PubMed1996

Agglutination of isolated platelet membranes.

Platelet membrane glycoproteins play a central role in platelet aggregation and thus in primary hemostasis. To investigate mechanisms of platelet-platelet interaction in the absence of cellular activation events, we studied immunological and functional aspects of isolated platelet membranes. Platelet membranes contained significant amounts of the inducible fibrinogen receptor, glycoprotein (GP) IIb-IIIa, which exposes conformation-dependent LIBS1 and PMI-1 epitopes in response to fibrinogen-mimetic peptides GRGDSP and HHLG-GAKQAGDV. In the presence of soluble fibrinogen, membrane-coated latex beads showed Ca(2+)-dependent agglutination that could be partially inhibited by GRGDSP but not by the biologically inactive peptide GRGESP. Thrombospondin enhanced agglutination of membrane-coated beads, which could be inhibited by polyvalent anti-thrombospondin Fab fragments and anti-thrombospondin monoclonal antibody MA-II. Mg2+ inhibited both GPIIb-IIIa- and thrombospondin-mediated agglutination of membranes in a dose-dependent manner. The results of the present study indicate that isolated platelet membranes are a useful tool to study regulation of GPIIb-IIIa- and thrombospondin-mediated platelet-platelet interaction.

Agglutination↗