Showing papers by "Ludwig Maximilian University of Munich published in 1975"

Prolongation of hippocampal inhibitory postsynaptic potentials by barbiturates.

Abstract: IT is well documented that barbiturates dramatically prolong presynaptic inhibition1–4. Their effect on postsynaptic inhibition is less clear, although the available evidence suggests that a similar enhancement may occur at some sites5–7. Since the inhibitory postsynaptic potentials (i.p.s.p.s) in hippocampal neurones are unusually large and the neurones are readily penetrable by microelectrodes8, we have studied the effect of barbiturates on these i.p.s.p.s in detail. We have found that barbiturates hyperpolarise hippocampal neurones and markedly prolong the i.p.s.p. by a direct action on inhibitory synapses, anaesthetic doses increasing the duration fivefold. The hyperpolarising action of barbiturates and their effect on i.p.s.p.s would both contribute to the neural depressant action of these anaesthetic agents.

Hydroperoxide-Metabolizing Systems in Rat Liver

Abstract: 1 Metabolism of added hydroperoxides was studied in hemoglobin-free perfused rat liver and in isolated rat hepatocytes as well as microsomal and mitochondrial fractions. 2 Perfused liver is capable of removing organic hydroperoxides [cumene and tert-butyl hydroperoxide] at rates up to 3–4 μmol × min−1× gram liver−1. Concomitantly, there is a release of glutathione disulfide (GSSG) into the extracellular space in a relationship approx. linear with hydroperoxide infusion rates. About 30 nmol GSSG are released per μmol hydroperoxide added per min per gram liver. GSSG release is interpreted to indicate GSH peroxidase activity. 3 GSSG release is observed also with added H2O2. At rates of H2O2 infusion of about 1.5 μmol x min−1× gram liver−1 a maximum of GSSG release is attained which, however, can be increased by inhibition of catalase with 3-amino-1,2,4-aminotriazole. 4 A contribution of the endoplasmic reticulum in addition to glutathione peroxidase in organic hydroperoxide removal is demonstrated (a) by comparison of perfused livers from untreated and phenobarbital-pretreated rats and (b) in isolated microsomal fractions, and a possible involvement of reactive iron species (e.g. cytochrome P-450-linked peroxidase activity) is discussed. 5 Hydroperoxide addition to microsomes leads to rapid and substantial lipid peroxidation as evidenced by formation of thiobarbituric-acid-reactive material (presumably malondialdehyde) and by O2 uptake. Like in other types of induction of lipid peroxidation, malondialdehyde/O2 ratios of 1/20 are observed. Cumene hydroperoxide (0.6 mM) gives rise to 4-fold higher rates of malondialdehyde formation than tert-butyl hydroperoxide (1 mM). Ethylenediamine tetraacetate does not inhibit this type of lipid peroxidation. 6 Lipid peroxidation in isolated hepatocytes upon hydroperoxide addition is much lower than in isolated microsomes or mitochondria, consistent with the presence of effective hydroperoxide-reducing systems. However, when NADPH is oxidized to the maximal extent as evidenced by dual-wavelength spectrophotometry, lipid peroxidation occurs at large amounts. 7 A dependence of hydroperoxide removal rates upon flux through the pentose phosphate pathway is suggested by a stimulatory effect of glucose in hepatocytes from fasted rats and by an increased rate of 14CO2 release from [1-14C]glucose during hydroperoxide metabolism in perfused liver.

The Formation of Hematite from Amorphous Iron(III)Hydroxide

Abstract: The formation of hematite from amorphous Fe(III)hydroxide in aqueous systems at pH 6 and 70°C, both with and without oxalate, was followed by kinetic measurements, electron microscopy, i.r. spectroscopy and thermal analysis. In the absence of oxalate, small amorphous particles coalesce into aggregates which eventually become single crystals of hematite. When oxalate is present, crystal growth is much faster and does not proceed through the intermediate stage of aggregation. Aggregates, when formed, consist of groups of single crystals. It is suggested that oxalate accelerates the nucleation of hematite crystals by acting as a template, the Fe-Fe distance in Fe-oxalate ions being similar to that in hematite.

Abstammung, Eigenschaften und Verwendung des attenuierten Vaccinia-Stammes MVA

Abstract: Das MVA-Virus reprasentiert ein Labor-Virus, das sich durch zahlreiche biologische Marker von den bekannten Vaccinia-Stammen wie auch von den anderen Viren der Orthopox-Gruppe sicher differenzieren last. Es kommt nicht in der Natur vor und besitzt fur Mensch und Tiere bei fehlender Kontagiositat nur noch eine geringgradige Virulenz. Es kann ohne Gefahr sowohl parenteral wie auch lokal, insbesonders oral und intrakutan, appliziert werden. Nach lokaler Verabreichung induziert es sehr stark die Bildung von endogenem Interferon. Voraussetzung hierfur ist die Impfung mit hohen Virusdosen (uber 107,5FHEKID50/ml).

Microrheology and light transmission of blood. III. The velocity of red cell aggregate formation.

Abstract: Employing both microscopic and photometric methods the rheology of pathological red cell aggregation was studied in model experiments. Suspensions of washed human red blood cells in dextran solutions containing rising concentrations of dextrans (M.W. 40000, 70000, 110000, 250000, 500000) were used. At low concentrations ( 70000)red cell suspensions formed aggregates similar to the ones found in normal human blood. At higher concentrations, the aggregates were similar to those observed in pathological human blood. The aggregates were studied under the condition of stasis, slow flow and at shear rate of their hydrodynamic dispersion. Besides, the flow behavior of the dispersed cells at high shear rates was studied. We found: 1. In all samples the rate of spontaneous aggregate re-formation in stasis (following hydrodynamic desaggregation) rose with rising dextran concentration up to 5.0 g-%. 2. The shear resistance of the aggregates, as measured by the shear stress necessary to keep them dispersed, rose up to concentrations of 2.5 g-%, but fell at higher concentrations. 3. Only with dextran of a molecular weight above 110000 coarse agglomerates could be produced at high concentrations. Loose elastic meshes were rapidly produced at high concentrations of Dx 70. 4. When subjected to steady state low shear (7 sec−1) only the agglomerates, but not the meshes rapidly grew in size.

Photoemission from Rare-Gas Solids: Electron Energy Distributions from the Valence Bands

Abstract: Photoelectron energy distributions for solid Ne, Ar, Kr, and Xe have been measured for $8 \mathrm{eV}l~\ensuremath{\hbar}\ensuremath{\omega}l~30 \mathrm{eV}$ by use of synchrotron radiation. From these we obtained the total width and structure of the valence bands. Our data demonstrate that almost all available band-structure calculations fail to predict quantitatively features other than the spin-orbit splitting. Photoelectron energy distributions for Xe in Ar and Xe in Ne support this viewpoint.

Histographic surgery: accuracy of visual assessment of the margins of basal-cell epithelioma.

Abstract: In 72 basal-cell epitheliomas, the clinical extension and the actual extension of the defect measured by complete tumor removal by Mohs' chemosurgery were compared. Subclinical extension depends on the type of basal-cell epithelioma (primary, recurrent), on case history, location, clinical diameter, number of previous treatments and histological type. It is remarkably great in large (diameter more than 20 mm), in morphea-like basal-cell epitheliomas on the forehead, temple and scalp, especially following several previous treatments. In such cases the excision should include at least a 5-10 mm margin of "normal tissue." Present results again show that "histographic," that is, Mohs' chemosurgery is the method of choice for the treatment for these tumors.

Coronary responses to dilating substances and competitive inhibition by theophylline in the isolated perfused guinea pig heart.

Abstract: Coronary dilation induced by infusion of adenosine, adenine nucleotides, dipyridamole, and papaverine was quantitated in the spontaneously beating isolated perfused guinea pig heart. Theophylline antagonized the effects of all the substances tested. The inhibition proved to be reversible and of a competitive type. Single injections of ADP and ATP induced flow increases which were more rapid in onset and of greater magnitude than those due to equimolar amounts of adenosine. Lowering the perfusate temperature prolonged coronary responses to ADP and ATP more than those to adenosine. Papaverine produced greater maximal dilation than adenosine. Theophylline inhibited papaverine-induced dilation less effectively than dilating responses to adenosine and other compounds. In the potassium arrested heart, the dilation caused by compound D 600 and papaverine was sensitive to the perfusate calcium concentration but that due to adenosine was unaffected. Dipyridamole, which was equipotent to adenosine in the non-arrested heart, became less potent than adenosine in the arrested heart. The results favour the view that all of the substances tested induce coronary dilation per se and that their effects are not mediated by adenosine. The dilator response to papaverine is assumed to be the result of two effects, one of which is inhibited by theophylline, the other by high extracellular calcium.

Salt and Water Balance

Abstract: In warm-blooded animals water makes up about 60 percent of the body weight and exists as a solution of organic and mineral substances. This water is in constant exchange with the environment as a result of periodic uptake from the gut and continual loss through the skin, respiratory passages, and kidney. Within the body the water is distributed in several more or less discrete compartments whose contents are called the “body fluids.” The anatomical boundaries separating these compartments and the differences in the solutes present in each are of fundamental biological significance.

Effect of increased blood fluidity through hemodilution on general circulation at rest and during exercise in dogs.

Abstract: During progressive normovolemic hemodilution with dextran-60, circulatory functions (cardiac output, oxygen delivery to tissues, arterial pressure and mixed venous oxygen saturation) and total body oxygen consumption were studied in conscious dogs at rest and during two levels of submaximal treadmill exercise. At rest, cardiac output rose continuously with progressive hemodilution. This increase, however, was not sufficient to compensate for the reduced arterial oxygen content. Consequently oxygen delivery fell significantly from 23.3±1.8 ml/min·kg at hematocrit 47.5% to 15.7±0.9 ml/min·kg at hematocrit 12.5%. The constant oxygen consumption was maintained by a simultaneous increase in oxygen extraction from blood. During the superimposed stress of exercise, a constant oxygen consumption was maintained between hematocrit ranges of 50 to 15 or 25%, respectively. Again, the increase of cardiac output due to hemodilution did not compensate for the reduced arterial oxygen content and consequently oxygen extraction rate was increased. These data demonstrate that at rest (and even more during submaximal treadmill exercise) the reduced whole blood viscosity or improved fluidity during hemodilution does not initiate an increase in cardiac output that is sufficient to maintain a constant oxygen delivery to the tissues.

Carbon isotope discrimination in alpine succulent plants supposed to be capable of crassulacean acid metabolism (CAM)

Abstract: 1. The 4 alpine species of Sempervivum (S. arachnoideum L., S. montanum L., S. soboliferum Sims, S. wulfenii Hoppe) analyzed in this study showed acidification during the dark period in their natural habitat. The δ13C value of these species varied according to the water supply at their natural habitat, being less negative at dry sites. These data are consistent with a larger contribution of dark CO2 fixation via Phosphoenolpyruvate-Carboxylase in relation to light CO2 fixation via Ribulose-1, 5-diphosphate Carboxylase. These alpine Sempervivum spp. behave, therefore, like typical CAM-plants. 2. In contrast, the 3 alpine species of Sedum analyzed in this respect (S. acre. L., S. alpestre Vill., S. rosea (L.) Scop.) showed no pronounced dark acidification. The δ13C value of the 8 alpine Sedum species examined in this study (the 3 mentioned above and S. album L., S. atratum L., S. dasyphyllum L., S. reflexum L., S. sexangulare L.) was much more negative than in the Sempervivum spp., indicating that the dark CO2 fixation does not play a great role in the carbon metabolism of the alpine Sedum spp. in the natural habitats. Water supply in the natural habitat has no clear-cut influence on the δ13C value. 3. All alpine species of Saxifraga analysed (S. seloides L., S. oppositifolia L., S. bryoides L., S. aizoides L., S. squarrosa Sieber, S. paniculata Mill., S. caesia L.) show δ13C values typical of C3 plants and they were not influended by the water conditions in the natural sites. Saxifraga paniculata showed no dark acidification in its natural habitat and we suspect that alpine Saxifrages are not CAM plants. 4. Based on δ13C values the alpine plants Pinguicula alpina L., Thesium alpinum L., and Linaria alpina (L.) Mill. are typical C3 plants.

An isolated guinea pig heart preparation with in vivo like features.

Abstract: Hemodynamic and metabolic characteristics of an isolated guinea pig heart preparation perfused with a pyruvate fortified Krebs-Ringer-bicarbonate solution are described. The preparation is stable for more than 90 min with respect to coronary flow, heart rate, left ventricular pressure,dP/dt, oxygen consumption, and myocardial high energy phosphate levels. The changes in coronary flow induced by alterations of perfusion pressure, ischemia, and hypoxia resemble those seen under in vivo conditions. The preparation also exhibits concentration dependent and reproducible changes in coronary resistance upon administration of adenosine and papaverine. The in vivo like features of this preparation can be mainly attributed to the use of pyruvate as additional and preferentially utilized substrate. The preparation appears to be suitable for quantitative studies of myocardial metabolism and heart function as well as for investigations of the coronary system.

Liver cirrhosis: immunofluorescence and biochemical studies demonstrate two types of collagen.

Abstract: Pepsin solubilization of small and large noduled liver cirrhosis yielded two types of collagen (precipitated at 17 and 25 M NaCl concentrations) as demonstrated by electronmicroscopy The 17 M NaCl precipitate was identified as type III collagen using an immunofluorescence technique The 25 M NaCl precipitate appeared to be type I in the electronmicroscope However, immunofluorescent and biochemical studies indicated that it was not type I but a type of collagen not yet described

Immunohistochemical evidence for the presence of collagen type III in human arterial walls, arterial thrombi, and in leukocytes, incubated with collagen in vitro.

Abstract: Sections of arterial walls and of thrombi and smears of leukocytes previously incubated in vitro with collagen type III were examined by immunohistochemical technique for the presence of collagen types I, II and III. In arterial walls collagen type III was detected immediately underlaying the endothelial cell layer and in the tissue between tunica elastica interna and adventitia. Collagen type I was not shown in the subendothelial layer. Fresh thrombi contained occasionally collagen, but only of type III. This was associated with leukocytes. Leukocytes were capable in vitro to associate and/or phagocytose collagen type III and this could be visualized immunohistochemically. The data show that collagen type III in vivo may play a crucial role in the initiation of thrombus formation.

The Binding of Atractylate and Carboxy-atractylate to Mitochondria

Abstract: 35S-labelled atractylate and carboxy-atractylate are produced biosynthetically and used for studying the binding of these specific ligands to the ADP, ATP carrier in beef heart mitochondria. The following results are obtained. 1 Inhibition of translocation activity goes parallel to the increase of binding by [35S]atractylate. No additional binding is observed after full inhibition of translocation is reached giving evidence that atractylate binds exclusively to the carrier. 2 The maximum number of binding sites of both atractylates is about 1.6 μmol/g protein in beef heart mitochondria and decreases on treatment of the membrane by Pi, freezing, ageing, etc. The dissociation constants of the binding are approximately for atractylate Kd= 5.10−8M and for carboxy-atractylate Kd= 10−8M. The mass action plots of the concentration dependence for the binding are nonlinear-convex in particular with carboxy-atractylate and more linear with atractylate. Nonlinearity appears to be caused by some retardation of equilibration in the case of very high affinity binding. 3 The binding of atractylate and carboxy-atractylate is relatively fast in intact mitochondria and slower in aged membranes. There is a slower and a faster binding portion. 4 The atractylates remove ADP in a nearly 1:1 stoichiometry from untreated mitochondria. In aged and Pi-treated membranes the ratio Δ; ADP/Δatractylate approaches 0. Obviously binding of carrier sites to ADP is more sensitive to alterations then that of the atractylates. The assumption is maintained that the binding site for atractylate is identical with that for ADP and ATP. 5 Bongkrekate prevents binding of both atractylates. However, when added after, it only removes atractylate but not the carboxy compound because of its different tight binding. The removal of atractylate depends on the synergistic effect of bongkrekate with ADP. 6 The binding studies with [35S]atractylate and in particular the interaction with bongkrekate support the reorienting carrier model in which atractylate as an impermeable ligand fixes the binding site of the carrier outside while with bongkrekate the carrier site is turned to the inside.