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Biomedical subjects

U Heinzmann

Publications and source records attributed to U Heinzmann.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1995

Effect of fibrinogen substitution in afibrinogenemia on hemorheology and platelet function.

Fibrinogen substitution can correct bleeding in afibrinogenemia. We assessed the effect of fibrinogen substitution in a patient lacking immunoreactive fibrinogen. Fibrinogen and thrombin time were not measurable before, but became detectable within 30 min after substitution, parallelled by an increase in ADP-induced platelet aggregation from < 10% to 32%. Platelet adhesion, measured by Stagnation Point Flow Adhesio- Aggregometry, was not detectable prior to substitution but attained normal values thereafter. Scanning electron microscopy of adhering platelets revealed pseudopodia protrusion and spreading. Morphometry revealed two populations of spread platelets one of which demonstrated inhibited spreading as compared to healthy controls. Immunoelectron microscopy revealed normal GPIIb/IIIa receptor expression, both before and after substitution. Dynamic and kinematic viscosity of plasma and whole blood remained below the 99.9% confidence border of a healthy control group. In afibrinogenemia fibrinogen levels as low as 10% of normal concentration sufficed to normalize coagulation, platelet adhesion, and, partially, spreading.

Adult↗
PubMed1995

Residence time in niches of stagnant flow determines fibrin clot formation in an arterial branching model--detailed flow analysis and experimental results.

Deposition of blood components in branching flow has been investigated primarily with regard to platelets. We instead examined thrombin-induced fibrin clot formation in separated laminar as well as turbulent branching flow. The most rapid clot growth and largest clot was obtained at the lowest inflow rate. Increased inflow reduced the clot size and turbulence completely prevented clot formation. Examination of corresponding flow conditions revealed the recirculation zone in laminar flow to be characterized by two stationary, counterrotating vortices. Niches of stagnant flow, exhibiting long residence times, low wall shear rates and characterized by convergent flow, were spared between the bulk flow and these vortices. Here, fibrin clot growth continued even when shear rates were increased more than 100-fold. Our results indicate that, in branching flow, the long residence times and convergent flow characteristic of flow niches rather than shear rate are critical for fibrin clot formation.

Arteries↗
PubMed1994

Flow mediated fibrin thrombus formation in an endothelium-lined model of arterial branching.

In vivo arterial thrombosis occurs preferentially at curvatures and branchings, i.e. regions of flow separation and recirculation where blood is retained orders of magnitude longer than within straight vessel sections. To examine the effect of such disturbed flow on endothelial thromboresistance glass T-branchings lined with endothelial cells from human umbilical cord veins (HUVEC) were perfused with buffered fibrinogen solution (3mg/ml). The flow was adjusted to form a large recirculation zone and flow conditions were determined beforehand by means of flow visualization via dye injection as well as by laser ultramicroscope anemometry. Thrombus formation, which was registered on-line by video and evaluated planimetrically, was induced by injection of thrombin at concentrations ranging from 0.3 to 2.0 units/ml. Fibrin thrombus growth always began within the flow niche at the point of flow separation and extended downstream along the wall and into the vessel lumen finally occluding up to 80% of the lumen. Light and electron microscopy revealed that overall thrombus form as well as the orientation of single fibrin fibers were correlated strictly to the prevailing streamlines. Despite the integrity of the endothelial lining fibrin thrombus formation occurred. The fibrin fibers closely contacted the endothelial surface. These results indicate that recirculation zones promote fibrin thrombus formation sufficient to obstruct the vessel lumen and that intact endothelium alone is insufficient in preventing adhesion of fibrin to its surface.

Arteries↗
PubMed1994

Detection of epidermal growth factor receptor by scanning electron microscopy.

A method of immunocytochemistry and low-voltage scanning electron microscopy (SEM) is described for visualization of the epidermal growth factor membrane receptor (EGFR). The specific labelling is achieved of antigenic sites on the surface of prefixed cells. The advantage of this approach over existing techniques is the capability for unlimited high-resolution surface examination at the single cell level. This is achieved by using low acceleration voltage (V0) and either very thin or no coating of the specimens to prevent the label from being masked. Furthermore, by using conventional field emission SEM and a highly sensitive detector for backscattered electrons, detection of the gold-conjugate (< 10 nm in diameter) becomes possible even at low V0. A431 cells (human epidermoid carcinoma) show intercellular variability in their EGFR area density. Highest density was recorded upon cells in the mitotic stage of the cell cycle due to a decrease in the relative surface of rounded versus flattened cells. At the ultrastructural level a marked heterogeneity was also seen on the surface of contracted cells, where enhanced labelling could be observed only at the tips of microvilli. In contrast, spread cells displayed a homogeneous receptor distribution due to their smooth surface.

Carcinoma, Squamous Cell↗
PubMed1994

Morphologic effects of a sulfur(IV) aerosol on the nasal cavity of beagle dogs.

Morphologic changes were observed in nasal cavities of beagle dogs after long-term exposure to a respirable sulfur(IV) aerosol at a concentration equivalent to a sulfur dioxide (SO2) concentration of 0.6 mg/m3. The changes were characterized by a thickened epithelial layer resulting from epithelial proliferation, by a loss of secretory material, and by moderate mononuclear cell infiltration.

Administration, Inhalation↗
PubMed1993

Reduction of HIV-1 antigen production by phosphatidylcholine containing formulations via growth inhibition of HIV-1-infected cells.

Phosphatidylcholine (PC) and licensed formulations containing PC were tested for their influence on the proliferation and viability of cells permanently infected with HIV-1 (human immunodeficiency virus type 1). PC alone, as well as pharmaceutical formulations containing PC, selectively inhibited the growth of productively infected lymphoid cells. The strongest growth inhibition was observed with formulations containing PC, glycerol and triglyceride together. The growth inhibition was dose-dependent for HIV-1-infected cells. Additionally, PC-containing formulations dramatically reduced antigen production from peripheral blood mononuclear cells (PBMCs) infected in vitro with HIV-1. In vivo experiments with Rauscher-MuLV-infected mice showed that PC administered either intraperitoneally or orally was able to inhibit Rauscher-virus-induced splenomegaly. PC-containing formulations are currently used in man for supportive therapy at doses, which in vitro induced 50% growth inhibition of HIV-1-infected cells in vitro. Such doses have been used in man without side effects for many years. Thus, PC-containing formulations may be valuable for the treatment of HIV-1-infected individuals.

Animals↗
PubMed1992

Prenatal pathogenesis of hydro-micrencephaly induced by X-rays. An animal model.

Experimental results are presented which describe induction and pathogenesis of the hydro-micrencephaly in NMRI-mice after single X-irradiation with 0.9 Gy or 1.9 Gy on gestation day (gd) 12. The ultrastructural alterations in the ventricular walls are sequentially investigated up to gross developmental damage. The ventricular zone is the most sensitive region in the developing brain. Its constituting undifferentiated and proliferating cells lose their palisade like orientation and fail subsequently to differentiate into primitive neurons, glia cells, or ependymal cells. Structurally this results in the thinning of ventricular walls by more than 50% associated with periventricular oedema and a dilation of the brain ventricles by 20-60%. Damage is clearly more pronounced with the higher dose. Repair processes originate from regions with intact Zonulae adherents which give also rise to typical globular or cylindrical heterotopic structures; these are known as rosettes and made up from undifferentiated proliferating ventricular cells. Perinatally in these rosettes cell replication persists, at a time when cell production in the ventricular zone has ceased. Histological changes are most prominent in and around the telencephalic roof consisting in replacement of the ependymal lining by a felt of glial fibers, faulty myelinisation, and periventricular oedema; postnatally these structural alterations lead to hydro-micrencephaly. Results from this animal model can be translated to the human situation because the fundamental developmental processes in the brain of mammals are similar despite species related differences of the time scale.

Abnormalities, Radiation-Induced↗