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    Biophysical investigations of the in vitro effects of shock waves and ultrasound
    (1993) Brümmer, Franz; Suhr, Dierk; Irmer, Ulrich; Bachleitner, Christoph; Hülser, Dieter F.
    To investigate the interactions of ultrasonic waves with biological tissues, we developed and standardized several in vitro models. Using these systems - artificial stones, human erythrocytes, L1210 mouse leukemia cells, multicellular spheroids, cavitation assay - we are able to elucidate the mechanisms of interaction as well as the cause of clinically observed side effects.
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    Biological effects of shock waves
    (1990) Brümmer, Franz; Bräuner, Thomas; Hülser, Dieter F.
    Extracorporeal shock wave lithotripsy has become established worldwide as the method of choice for the treatment of nephrolithiasis and ureterolithiasis over the last 10 years. Although initial studies showed no damaging effects of the shock waves on organs and tissues, numerous recent reports have presented evidence for severe acute effects and chronic complications after shock wave treatment. The pathophysiological effects on kidneys and the histopathological effects on organs or tissues in man and animal, and also the effects on cells in culture and tumors are sumarized. Suspended and immobilized cell cultures were used to characterize and quantify the efficacy of shock wave. Extended applications of shock waves and possible modifications to shock wave generators are discussed.
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    Introduction - Symposium on Intercellular Communication Stuttgart, 1982
    (1982) Hülser, Dieter F.
    Intercellular communication is a postulate of complex multicellular organisation. Signal transfer between cells is possible in different ways: 1.) Long distances of up to 1 m may be bridged by molecules which are produced in distinct cells and are released into the extracellular fluid where they are distributed and interact with receptors on the surface of their target cells (e.g., humoral interaction). 2.) Transmitter substances which have a limited life span or which can be inactivated by inhibitor molecules spread signals only over shorter distances (e.g., synaptic cleft, -200nm). 3.) Information can also be exchanged by direct membrane contact when two molecules interact with each other directly or via linker molecules (e.g., immune system). 4.) Intercellular communication is also possible by channels between adjacent cells, which permit the exchange of ions and molecules and the spread of electric currents; many of those pores are arranged in the membranes of the contacting cells as a quasicristalline structure forming the gap junction. A national symposium on "Intercellular Communication" in Stuttgart on 16 and 17 September 1982 serving the aim of increased "interlaboratory communication" covered most of the above aspects.
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    Extraordinary biological membrane structures resulting from different local membrane curvatures
    (1992) Meyer, Helmut W.; Hülser, Dieter F.
    The bilayer arrangement of amphiphilic molecules is not only the basic structure of rather flat biological membranes, but also of regularly curved bilayers in most cubic phase structures. The basis of these cubic phase structures are infinite periodical minimal surfaces (IPMS). Extraordinary biological membrane structures resembling such IPMS were found as periodically curved bilayers in areas of the plasma membrane in a Streptomyces strain and in liposomes prepared from its extracted lipids. This structure consists of a transition of convex to concave curvatures and vice versa. A structure with curvatures in one direction only was observed in vacuolar membranes of yeast cells with a genetic defect. Our electron microscopical analysis of freeze fractured membranes of these cells revealed not only fully invaginated but also flat particle-free areas which were mainly circularly shaped, some elongated areas, however, were also present. In addition, sometimes periodical arrangements were detected which obviously are not related to IPMS structures. Both structures, however, indicate a high proportion of wedge-shaped lipid molecules in the bilayer.
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    The use of the tip potential of glass microelectrodes in the determination of low cell membrane potentials
    (1973) Hülser, Dieter F.; Webb, Dennis J.
    The tip potential of Ling-Gerard glass microelectrodes changes upon insertion into cells and thus impedes the determination of the actual membrane potential. The lower the membrane potential of a cell, the larger will be the error due to this tip potential. However, as is demonstrated, a relationship exists between the tip potential of the electrode and the measured potential difference, which allows the determination of the membrane potential of a particular cell type by linear regression. This method showed that resting lymphocytes had no membrane potential, whereas for the slime mould Dictyostelitium discoideum a membrane potential of about -9 mV could be calculated.
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    Reduced cavitation-induced cellular damage by the antioxidative effect of vitamin E
    (1994) Suhr, Dierk; Brümmer, Franz; Irmer, Ulrich; Schlachter, Manfred; Hülser, Dieter F.
    Fragmentation of human urinary and biliary stones by shock waves in extracorporeal lithotripsy is accompanied by tissue damage. Both the fragmentation as well as the side effects are often attributed to cavitation. The hazardous potential of cavitation is not only of a physical nature but also of a chemical nature, because of the generation of free radicals, e.g. ·OH, ·H and ·O2. After the application of shock waves, we have demonstrated cavitation-generated free radicals in cell-free solutions and also in the surviving and intact suspended MGH-U1 cells by hydroethidine measurements. Under electron microscopical inspection, the same cells exhibited perinuclear cisternae, damaged mitochondria and numerous intracellular vacuoles. The contribution of free radicals to cell damage was investigated by reducing the vitamin E level in rats by a tocopherol free diet and by incubating L1210 cells in a tocopherol enriched medium. After 250 shock waves, ex vivo erythrocytes revealed a 75% increase in total cell disruption over cells from non-depleted rats. The in vitro experiments with L1210 cells exhibited a moderate protection by the addition of this scavenger of free radicals.
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    Membrane potential oscillations in homokaryons : an endogenous signal for detecting intercellular communication
    (1982) Hülser, Dieter F.; Lauterwasser, Ursula
    Fusion of cells by polyethylene glycol results in homokaryons with lower membrane input resistances than their parental cells, but otherwise unchanged membrane properties. With these large cells, long lasting intracellular recordings can be realized which are impossible with single parental cells. Homokaryons often display hyperpolarizing (up to 50 mV) oscillations of their membrane potentials. In electrically non-coupled cell lines (HeLa, L, Cl-1D) the frequencies of these endogenous signals are 3 oscillations per min. Trypsinized homokaryons of electrically coupled cell lines (BICR/M1R-K, 3T3, BT5C2) have frequencies of 0.3 oscillations per min. By recording the membrane potential oscillations of two contacting homokaryons, the formation of low resistance junctions was followed - without applying exogenous signals - by a superposition of the individual oscillations. Our electronmicroscopical investigations revealed that the intercellular coupling through the membranes of homokaryons can be attributed to gap junctions.
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    β-galactosidase production in two- and threedimensionally cultivated cell cultures
    (1991) Klünder, Irene; Hülser, Dieter F.
    In these studies, we demonstrate that the threedimensional arrangement of the cells in spheroids influences the β-galactosidase activity of transfected ltk--cells. In contrast to cells grown in monolayer culture cells growing as spheroids lost their β-galactosidase activity within few days. The reduction of β-galactosidase activity in cells grown as spheroids was not caused by a lost of the lacZ-gene as can be seen from the recovery of the β-galactosidase production when cells were retransferred in monolayer culture. As we showed in cells cultivated as monolayer, β-galactosidase activity seems to be not impaired by gradients of nutrient supply or cell cycle. These measurements are confirmed by histological sections, where the highest β-galactosidase activity was found in the viable center of the spheroids.
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    Transduction of chemical signals in dictyostelium cells
    (1984) Gerisch, Günther; Tsiomenko, Arnold; Stadler, Joachim; Claviez, Michael; Hülser, Dieter F.; Rossier, Claude
    Three different functions of cyclic AMP in D discoideum are known: (1) cAMP acts as a chemoattractant during cell aggregation, (2) it controls cell development, particularly the acquisition of aggregation competence, and (3) it is involved in terminal cell differentiation. In this report we will concentrate on the functions 1 and 2 of cAMP. Chemotaxis requires the recognition of concentration gradients in the environment by attractant binding to cell surface receptors, the processing of signals from the receptors to the contractile system of the cells, extension of pseudopods at one part, and contraction at other parts of the cells in accord with the external gradient. One pathway of signal processing from the receptors to the contractile system involves the regulation of a myosin kinase. The control of development up to aggregation competence is largely dependent on the temporal pattern of cAMP application: Only repetitive pulses enhance development. This effect has been studied using the expression of a membrane glycoprotein called contact site A as a differentiation marker.
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    Cyclic-AMP reception and cell recognition in dictyostelium discoideum
    (1975) Gerisch, Günther; Malchow, Dieter; Huesgen, Adolfine; Nanjundiah, Vidyanand; Roos, Werner; Wick, Ursula; Hülser, Dieter F.
    Single cells of the slime mold, Dictyostelium discoideum, aggregate into a multicellular organism in response to cyclic AMP, which they detect by binding to cellsurface receptors. During the aggregation phase, two different responses to cyclic-AMP are observed. First, the cells orientate by chemotaxis towards the source of a concentration gradient which initially is a group of cells forming an aggregation center. Second, the cells relay pulses which are periodically generated by the centers.