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Biomedical subjects

A Herrmann

Publications and source records attributed to A Herrmann.

At least 163 records · Page 9Linked to original sources

The influence of the antiviral drugs amantadine and rimantadine on erythrocyte and platelet membranes and its comparison with that of tetracaine.

The influence of the antivirus drugs amantadine and rimantadine and of the anionic analogue 1-adamantane-carboxylic acid on a range of properties of human erythrocyte membrane and of thrombocytes has been compared with the effect of the local anaesthetic tetracaine. At low antiviral drug concentrations the abilities of the drugs to induce erythrocyte shape change and suppress osmotic haemolysis were quantitatively proportional to their clinical potency (rimantadine more effective than amantadine at the same concentration). Rimantadine was also more effective than amantadine in suppressing influenza virus-erythrocyte fusion and viral induced haemolysis. The antiviral drug effects were qualitatively similar to those induced by tetracaine. At the quantitative level, tetracaine was more efficient than the antiviral drugs in inhibiting osmotic haemolysis, virus membrane fusion and platelet aggregation. In the absence of any specificity of the antiviral drug effects we argue for a lysosomotropic mode of drug action, i.e. that the drugs modify virus-membrane interactions by changing the endosomal or lysosomal pH.

Adamantane↗

Phospholipid outside-inside translocation in lymphocyte plasma membranes is a protein-mediated phenomenon.

We have measured the transbilayer diffusion of spin-labeled analogs of sphingomyelin, phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine in pig lymphocyte plasma membrane. At 4 degrees C and 37 degrees C the aminophospholipids are rapidly transported from the outer to the inner leaflet of the membrane, whereas the choline-containing phospholipids experience a slower diffusion. This selectivity is abolished after cell treatment by SH-group reagents indicating that the aminophospholipid translocation is protein-dependent and must be driven by a system analogous to the one existing in the human red cell membrane. The fact that the selectivity exists at low temperature, that it does not depend on cytoskeleton integrity and that there is a competition between the two aminophospholipids show that this translocation is not purely an endocytic process.

Animals↗

Musculoskeletal tumors: improved depiction with linear combinations of MR images.

With postprocessing, the authors produced a single hybrid image that combines the complementary information in conventional T1- and T2-weighted magnetic resonance (MR) images. A 1-T MR imager was used to produce T1- and T2-weighted images (repetition time, msec/echo time, msec: 500/30, 1,500/120) of patients with various primary bone tumors. Various weighted sums and differences of these images were then formed. Weighted subtraction allowed formation of hybrid images with high contrast between tumor and all adjacent normal tissues (muscle, fat, bone marrow), unlike the original T1- and T2-weighted images. Certain weighted sums of the acquired images simultaneously display the high signal-to-noise and clear anatomic detail of the T1-weighted technique along with the high contrast between extraosseous tumor and muscle of the T2-weighted image. A single hybrid MR image can contain useful characteristics both of T1- and T2-weighted images, making it easier for one to detect the extent of an abnormality.

Bone Neoplasms↗

EPR spectroscopic analysis of binding sites of a cancerostatic agent on erythrocyte membranes.

A biologically highly active antitumor agent, chloroethyl-nitrosourea-piperidine-N-oxyl, was found to bind covalently to sulfhydryl groups of membrane proteins of erythrocytes. The agent penetrates the erythrocyte membrane very easily within three minutes. Mainly two different binding sites are distinguishable with rather high rotational mobility of the NO-moiety and high polarity of their environment. The lowered broadening of bound label suggests pocket-like binding sites with a limited accessibility for paramagnetic ions. Besides common concepts that antitumor agents often bind to DNA and inhibit cell proliferation, further targets on plasma membranes are taken into consideration for antitumor agents.

Alkylating Agents↗

Erythrocyte shape dynamics: influence of electrolyte conditions and membrane potential.

The correlation of erythrocyte shape and transmembrane potential already published (J. Membrane Biol 51 (1979), 217 and 66 (1982) 79) has been confirmed by using glutaraldehyde fixation and experiments without ionophores. It is demonstrated additionally that the influence of amphipathic drugs on the shape formation depends on the membrane electric field. The results can be interpreted assuming a negatively charged membrane compound being distributed between the two leaflets by electrochemical equilibrium.

Electrochemistry↗

Conformational alterations within the glycocalyx of erythrocyte membranes studied by spin labelling.

The structure of the glycocalyx of the membrane of human erythrocytes and spectrin-depleted vesicles was studied under various conditions by two spin-labelling approaches: covalently labelling sialic acid residues of the glycocalyx and incorporation of a charged hydrophobic spin probe, CAT 16, being sensitive to alterations on the membrane surface into the lipid phase. Although cell electrophoretic measurements which were performed, additionally, indicated an erection of the glycocalyx upon decreasing the ionic strength of the suspension medium a more restricted mobility of spin-labelled sialic acid residues was found, in this case probably due to electrostatic interactions. The enhanced mobility of the spin probe CAT 16 at low ionic strength as well as in the case of neuraminidase-treated cells could be caused by reduced steric and electrostatic interaction with glycoproteins and glycolipids. La3+ adsorption and virus attachment on the human erythrocyte membrane were accompanied with a reduced mobility of sugar headgroups of the surface coat. No indication of cluster formation or lateral segregation of glycophorin molecules was found upon virus binding. After denaturation of the spectrin cytoskeleton of intact erythrocytes, increased mobility of spin-labelled sialic acid residues was observed.

Electron Spin Resonance Spectroscopy↗

Correlation of the internal microviscosity of human erythrocytes to the cell volume and the viscosity of hemoglobin solutions.

The microviscosity of the cytoplasm of human erythrocytes as well as of membrane-free hemoglobin solutions was investigated measuring the rotation of the small spin-label molecule, Tempone. The dependence of the intracellular microviscosity on the extracellular pH and osmotic pressure which was varied by NaCl or sucrose was sufficiently explained on the basis of alterations of the red blood cell volume. The intracellular microviscosity depended exclusively on the hemoglobin concentration. It did not differ from that of comparable membrane-free hemoglobin solutions. It was not necessary to take into account long-range interactions between hemoglobin molecules. The conclusion therefore was that the intracellular viscosity is not modified by cytoplasmic structures or the cell membrane. Above a hemoglobin concentration of 6 mM the viscosity of hemoglobin solutions increased much faster than the microviscosity. From measurements obtained with different spin-labels it followed that also the charge of these molecules is of importance.

Cyclic N-Oxides↗

Ionic strength-dependent alterations of membrane structure of red blood cells.

Electron paramagnetic resonance (EPR) measurements using various fatty acid spin labels were performed on membranes of intact human erythrocytes at physiological, and at low ionic strength. In the case of spin probes bearing the nitroxide near the polar head group, a less restricted motion at low ionic strength was seen than with those labels with a nitroxide deeper within the hydrophobic tail of the membrane. Although these data clearly show an influence of ionic strength on membrane structure, and possibly a modified protein-lipid interaction, they cannot be simply discussed in terms of an altered membrane fluidity.

Electron Spin Resonance Spectroscopy↗

A model for the asymmetric lipid distribution in the human erythrocyte membrane.

The asymmetric transverse distribution of phospholipids in the human erythrocyte membrane can be explained by differences between the rate constants of flip and flop motion of the lipids. A selective interaction between aminophospholipids and spectrin does not need to be assumed for creating and maintaining the asymmetric localization of these lipids. Shape transformation of red cells could be caused by alterations of the flip-flop rate constants leading to a change of the lipid distribution and, consequently, to a differential area expansion of the outer and inner membrane leaflet.

Adenosine Triphosphate↗

Structural alterations of the human erythrocyte membrane upon influenza virus attachment.

Molecular events on the human erythrocyte membrane subsequent to influence virus binding were investigated by electron spin resonance (ESR) measurements after spin labeling of the cell membrane at different positions. Virus binding affected the glycocalyx structure as well as the physical state of the cytoskeleton at the inner leaflet, but not the lipid phase. A lateral reorganization of spin-labeled glycophorin was not indicated after virus attachment.

Absorption↗

Inactivation of the AIDS-causing retrovirus and other human viruses in antihemophilic plasma protein preparations by pasteurization.

Heat treatment at 60 degrees C for 10 h in solution (pasteurization) was introduced into the manufacturing process of antihemophilic cryoprecipitate (AHC) and factor VIII concentrates (F VIII) to reduce the risk of transmission of hepatitis to hemophiliacs. Since the acquired immunodeficiency syndrome (AIDS) may also be transmitted to hemophiliacs by antihemophilic plasma protein preparations, we have investigated inactivation of the AIDS virus HTLV III by pasteurization in AHC or F VIII and included in this study cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), poliovirus and vaccinia virus. Each of these viruses was efficiently inactivated by pasteurization although considerable differences were observed between the different viruses HTLV III was rapidly inactivated, becoming nondetectable within 30-60 min. Our findings indicate that pasteurized AHC or F VIII should have a high margin of safety regarding the transmission of AIDS or any other infectious disease caused by viruses such as those tested.

Acquired Immunodeficiency Syndrome↗

Interaction of the antivirus agents remantadine and amantadine with lipid membranes and the influence on the curvature of human red cells.

Surface potential difference, conductance, and elasticity changes of bilayer lipid membranes induced by the antivirus drugs amantadine and remantadine were measured. An influence on the human erythrocyte shape was shown. Both drugs are stomatocytogenic. The adsorption at the cytoplasmatic membrane was electrophoretically proved. The heat-induced vesiculation is partly inhibited. No microvesicles were observed. Instead, large tails which did not detach from the cell body were seen. The general conclusion is that these amphiphilic adamantane derivatives are membrane agents which modify membrane interaction processes, possibly by influencing the bending properties.

Adamantane↗

Volumetric development of the fetal telencephalon, cerebral cortex, diencephalon, and rhombencephalon including the cerebellum in man.

Fresh volumes of the human telencephalon, cerebral cortex, diencephalon, and of the rhombencephalon including cerebellum were determined in a series of 10 normal specimens ranging in age from 63 to 176 days after conception. The volumetric growth of these parts shows a nonlinear dependence on age with a smaller increase during the 3d ontogenetic month and a stronger increase from the 4th month on. These data were analyzed together with previous measurements of 28 brains taken from the Yakovlev Collection in Washington, D.C., and the Vogt Collection in Düsseldorf. These brains range in age from 137 to 22,900 days after conception. These samples were reproduced in a model using sigmoid logistic functions. The entire brain and all analyzed parts show a monotonous growth. The individual regions develop heterochronously. The diencephalon is the first part to reach its ideal volume, with a main growth spurt between 100 and 420 days after conception. The rhombencephalon including the cerebellum is the last, with its main growth spurt between 240 and 650 days after conception. The growth of the entire brain is determined to a great extent by that of the telencephalon, having a main growth spurt between 175 and 580 days after conception. The prenatal growth is described separately with the asymmetric sigmoid function according to Gompertz. This yields a better approximation of the data collected from the early prenatal period.

Cerebellum↗

The dielectric properties of aqueous solutions of poly(ethylene glycol) and their influence on membrane structure.

The dielectric constant of water is reduced drastically on addition of poly(ethylene glycol). The behaviour is not described by a linear mixture equation. The decreased dielectric constant can lead to the general perturbation of the membrane structure which is necessary in such a manner that a strong aggregation of membranes would lead to their fusion. The changed cation permeability in the presence of poly(ethylene glycol) can explained as the effect of the lowered dielectric constant on the transfer energy.

Electric Conductivity↗

Spectroscopic characterization of vesicle formation on heated human erythrocytes and the influence of the antiviral agent amantadine.

EPR investigations on the vesiculation process of heated human erythrocytes were performed, using different fatty acid spin labels. Spectrin denaturation and vesiculation do not influence the fluidity of the lipid phase of the remaining membrane of human erythrocytes: Vesicles released differ in chemical composition as well as in the lipid fluidity of their membrane from the intact human erythrocyte membrane. A reduced cholesterol-to-phospholipid ratio and a depletion of spectrin was found. By changing the ionic concentration of the suspension medium an effect on membrane spectra and on vesicle release was established. The adamantane derivative amantadine causes fluidization of the human erythrocyte membrane and inhibits vesicle release. Based on these results, a model for the mechanism by which adamantane-like molecules could interact with membranes is proposed.

Amantadine↗

Shape transformation of erythrocyte ghosts depends on ion concentrations.

Resealed human erythrocyte ghosts undergo shape transformations similar to those of intact erythrocytes. The results indicate that the shape of these ghosts depends on the inner as well as on the outer NaCl concentration. A correlation between shape and calculated transmembrane potential was established similar to that for intact human erythrocytes.

Cations↗

Influence of the intracellular and extracellular cation concentration on monovalent cation efflux of resealed human erythrocyte ghosts.

Tracer efflux measurements (86Rb+ and 22Na+) were performed on resealed human erythrocyte ghosts at different intra- and extracellular NaCl concentrations. Using a modified Goldman equation the observed alterations of the rate constants could be explained by taking into account the transmembrane and surface potentials, at constant permeability coefficient. These results emphasize the importance of membrane surface potentials in triggering ion transport across biological membranes.

Biological Transport, Active↗