Showing papers by "University of Tübingen published in 1972"

Stoffwechselprodukte von Mikroorganismen. 98. Mitteilung. Phosphinothricin und Phosphinothricyl-Alanyl-Alanin

Abstract: From cultures of Streptomyces viridochromogenes a new antibiotic, phosphinothricylalanyl-alanine, has been isolated. The new amino acid phosphinothricin is 2-amino-4-methyl-phosphino-butyric acid, its structure is confirmed by synthesis. The tripeptide is highly active against Gram-positive and Gram-negative bacteria and against the fungus Botrytis cinerea. Phosphinothricin is an active glutamine synthetase inhibitor.

Determination of drug metabolizing enzymes in needle biopsies of human liver.

Abstract: A micromethod is described for determination of the cytochrome P-450 content, demethylation rate of aminopyrine and p-nitroanisole, the activities of NADPH-cytochrome-c-reductase, pseudocholinesterase and glucose-6-phosphatase in homogenates of the small amount of human liver (about 20 mg) obtained by needle biopsy. 1 g of human liver contains 32–38 mg microsomal protein, much less than that present in rat liver (50–60 mg/g liver). The cytochrome P-450 content in normals was 10.8±2.6 nmoles/g liver wet weight (mean±1 S.D.). In severe hepatitis and cirrhosis the cytochrome P-450 content fell to 50% of the control value, whereas mild and moderate hepatitis did not produce any change. Similarly, only in seriously damaged livers were the demethylationrates of both substrates lowered. The activity of the NADPH-cytochrome-c-reductase was 1.88±0.51 micromoles/g liver × min and was not impaired even by severe liver damage. The activities of glucose-6-phosphatase and pseudocholinesterase also fell only in severe liver disease.

Liquid Phase Synthesis of Peptides

Abstract: ONE of the most exciting recent developments in peptide synthesis is the introduction of the solid phase method1 which facilitates rapid synthesis of peptides by the elimination of tedious purification steps. Excess reagents are removed by filtration. The ease of these operations led to speculations that the method might be used for the synthesis of enzymes, but careful investigation has shown that the individual coupling steps are not quantitative, so that erroneous sequences accumulate, together with the desired poly peptide2,3. General methods to separate such complex mixtures are still not available, especially if the chain length exceeds 20 amino-acids, so much was clear in the attempted synthesis of the enzyme ribonuclease4 and other larger peptides. Another disadvantage of the solid phase method compared with synthesis in solution is the restriction in the choice of solvents, coupling methods and protecting groups.

Induction of drug metabolizing enzyme system in the liver

Abstract: 1. Accelerated drug metabolism in liver cells was discovered during studies of the cause of barbiturate tolerance and of the way in which polycyclic hydrocarbons protect against the actions of several carcinogenic compounds. — 2. It is elicited by many lipid soluble drugs and is accompanied by increased synthesis of haem and enzyme proteins. It is due to increased activity of the drug metabolizing microsomal enzyme-complexes in the liver which consist of non specific mixed function oxidases and various transferases. — 3. Acceleration of drug metabolism is accompanied by hypertrophy of smooth intracellular membranes and enlargement of the liver. It is dependent on the concentration of the inducer in the endoplasmic reticulum and seems to be influenced by the stability of a complex formed between the drug and cytochrome P-450, as well as by certain, as yet unidentified properties possessed by certain types of inducing agents. — 4. In man it has been observed in patients during and after treatment with a few drugs which have a high inducing capacity and are prescribed in large doses. — 5. Accelerated drug metabolism might be highly advantageous and beneficial in protecting an organism against an overload of endogenous or exogenous toxic compounds, but it can also be harmful if it results in increased production of toxic metabolites. — 6. It can be regarded as a hitherto unknown pharmacological effect on the regulation of the synthesis-rate of enzymes involved in drug metabolism.

Divaricate patterns in pelecypod shells

Abstract: Shingled divaricate ribs occurring in several unrelated groups of pelecypods are highly functional structures related to specific burrowing processes. However, their obliqueness and ambivalence, seemingly the most aberrant features, are shared by a variety of colour, mineralization, and groove patterns both in the functional and non-functional field. Their basic form is assumed to be less controlled by adaptation and phylogeny than by a common principle of shell growth, the nature of which has still to be found out.

Bildung von Chloroform aus Tetrachlorkohlenstoff in Lebermikrosomen, Lipidperoxidation und Zerstörung von Cytochrom P-450

Abstract: 1. In reduzierten und anaeroben Suspensionen von Kaninchenlebermikrosomen werden 2% von zugegebenem CCl4 (1 mM) innerhalb von 5 min zu CHCl3 umgewandelt. Die Bildung von CHCl3 wird durch Metyrapon um 50%, durch CO um 75% und durch O2 um 95% gehemmt. 2. Orale Gaben von 2,5 ml/kg CCl4 an Ratten bewirken innerhalb der ersten 3 Std einen Abfall des endoplasmatischen Cytochroms P-450 um 30 bis 40%. Diese Verringerung wird durch Behandlung der Ratten mit Metyrapon, Desipramin, Piperonylbutoxid, Disulfiram oder Silymarin nicht verhindert. 3. Die Abnahme von Cytochrom P-450 kann in vitro durch aerobes Inkubieren von isolierten Lebermikrosomen mit NADPH in Gang gesetzt werden und wird durch CCl4 weiter beschleunigt. Zwischen dem Ausmas der Lipidperoxidation und der Abnahme von Cytochrom P-450 wurde eine gute Korrelation gefunden. ADTA oder GSH verhindern die Lipidperoxidation. Infolgedessen andert sich der Gehalt an Cytochrom P-450 sogar in Gegenwart von CCl4 gegenuber den Kontrollen nicht. UV-Bestrahlung von Mikrosomensuspensionen bewirkt Lipidperoxidation und schnelle Zerstorung von Cytochrom P-450. 4. Wahrend der Inkubation von Lebermikrosomen mit Linolensaure und Lipoxygenase aus Sojabohnen wurde eine ahnliche Beziehung zwischen der Abnahme von Cytochrom P-450 und der Lipidperoxidation beobachtet. Zugabe von Linolensaure oder Lipoxygenase allein hatte keine Wirkungen. Die Untersuchungen und Befunde sprechen fur einen gekoppelten Mechanismus der Lipidperoxidation mit gleichzeitiger oxidativer Zerstorung des Ham-Anteils.

Shock produced rock glasses from the Ries crater

Abstract: In the suevite breccia of the Ries impact crater, Germany, glasses occur as bombs, and small particles in the groundmass. These glasses were formed from melt produced by shock fusion of crystalline basement rocks. Ejection from the crater resulted in the formation of aerodynamically shaped bombs, a few homogeneous spherules and a large mass of small glass particles which were deposited in the suevite breccia. Bombs and small particles included within chilled bottom and top layers of suevite deposits have been preserved in vitreous state, whereas glasses within the interior of the suevite devitrified, due to slower cooling rates.

An electrophysiological study of regeneration in Acetabularia mediterranea.

Abstract: Polar regeneration of anucleate posterior stalk segments (PSS) of Acetabularia mediterranea has been studied electrophysiologically. 1. During regeneration the PSS develops a longitudinal, steady potential gradient, U, which is shown to reflect a spatial difference in the transmembrane potential, ΔVm,of 5 to 10 mV, i.e. about 5% of Vm.While regeneration becomes visible at about tr=45 h after its light-triggered onset, its sign can be predicted from U not later than at t=29 h, because regeneration occurs at that cell pole where Vmis highest, i.e. where the cytoplasm is more negative (Fig. 3, Table 1). 2. Clamping U to comparable values by external circuitry causes the regeneration again to occur where Vmis highest, although in this case the flow of the current, I, which controls U is opposite to the direction of the self-generated current, or even changes its sign (Fig. 11, Table 2). 3. Clamping U to zero, i.e. eliminating any transcellular potential gradient, inhibits polar regeneration at least up to t=60 h (Table 3). 4. Spontaneous spikes of U (Fig. 4) and of I (Fig. 12), occur as early as at t=8 h (Fig. 5). These spikes arise at the presumptive regenerating pole with refractory intervals of 10–25 min. They obviously reflect the propagating action potential (Figs. 7–9) although, under the conditions of our present experiments, they spread along the PSS only electrotonically (Fig. 6). 5. Both signals, U and the spikes, are presumably due to changes in the electrogenic Cl-dependent component of Vm,rather than its K+-controlled, diffusive component. 6. The data allow to substantiate our working-hypothesis (p. 242) that the mechanism of spatial differentiation involves voltage-dependent plasmalemma properties including excitation.

Polarization of hard x-rays from solar flares.

Abstract: The polarization of hard solar X-radiation (> 10 keV) is calculated on the assumption that electrons get a non-isotropic velocity distribution in the initial phase of a flare. The brems-strahlung generated by nonthermal electrons spiralling around magnetic field lines with discrete pitch angles is considerably polarized if observed at approximately right angles to the magnetic field. In the energy range from 10 to 50 keV the degree of polarization is not strongly dependent on the photon energy. For pitch-angle distributions of the form sin2α and cos2α, the polarization has opposite signs; it decreases appreciably at high photon energies. The observation of X-ray polarization will be useful in deducing the physical conditions in flares.

Eibildung und furchung von Trichoplax adhaerens F. E. Schulze (Placozoa)

Abstract: 1. Von Trichoplax adhaerens wurden zwei Klone gezuehtet. Der eine wurde 1969 (Klon I), der andere 1971 isoliert (Klon II). 2. Bei einer bestimmten Populationsdichte setzt eine degenerative Phase ein, die aus einem reversiblen und einem irreversiblen Abschnitt besteht. Werden die Tiere nicht rechtzeitig in eine frische Kulturschale ubertragen, so gehen sic zugrunde. 3. Der Ubergang in die degenerative Phase bildet die wesentliche Voraussetzung fur die Eibildung. 4. Obwohl in einem der beiden Klone vereinzelt auch eine spontane Eibildung beobachtet wurde (Klon I), fand sic in groserem Umfang erst statt, wenn beide Klone miteinander vermischt wurden. 5. Der klonale Unterschied entspricht keiner sexuellen Differenzierung; durch Vermischen beider Klone wurde auch in Klon II eine Eibildung induziert, indem sie bisher noch nicht spontan aufgetreten ist. 6. Spermien konnten noch nicht eindeutig identifiziert werden. Far das Vorkommen einer Befruchtung spricht aber, das sich nur Eier weiterentwickeln konnen, die eine besondere Hulle (“Befruchtungsmembran”) ausgebildet haben. 7. Die Furchung ist total-aqual. Unter den derzeitigen Kulturbedingungen sterben alle Furchungsstadien fruher oder spater ab. Das Ergebnis der Embryonalentwicklung ist daher noch unbekannt.

Organic Syntheses in the Plasma of Glow Discharges and Their Preparative Application

Abstract: It is only during the last few years that reactions of organic substances as a result of electron collisions in the cold plasma of glow and corona discharges have been developed into a preparatively useful method with a wide range of possibilities. Its basic principles and development prospects are discussed in the present progress report on the basis of the research results that are known at present.

Echoortung bei Rhinolophus ferrumequinum mit frequenzmodulierten Lauten. Evoked Potentials im Colliculus inferior

Abstract: 1. In 39 Experimenten an insgesamt 21 Grosen Hufeisennasen wurden evoked potentials im Colliculus inferior als Antworten auf frequenzmodulierte Reize abgeleitet. 2. Die Antwort auf einen 16 kHz-Endsweep eines simulierten naturlichen Lautes erfolgt spezifisch auf den Sweep oder einen Teil des Sweepes (Abb. 3, 4, 14). 3. Fur Frequenzmodulationen mit Sweephohen SH = 1000 Hz (s. S. 315) und Reizfrequenzen zwischen 78 und 85 kHz fallen die Schwellenkurven fur Auf- und Abwartssweeps mit der Schwellenkurve fur reine Tone zusammen (Abb. 6, 7). 4. Antworten auf Frequenzmodulationen mit Sweephohen kleiner als 400 Hz wurden nur fur Reizfrequenzen zwischen 80 und 84 kHz gefunden. Wahrend fur Aufwartssweeps bis herab zu 10 Hz evoked potential-Antworten erhalten wurden, traten fur Sweephohen unter 400 Hz nur selten Antworten auf Abwartssweeps auf (Abb. 5). 5. Fur Sweephohen kleiner als 1000 Hz engen sich die Schwellenkurven in ihrer Frequenzbreite ein. Das Schwellenminimum fur kleine Sweephohen (400–10 Hz) liegt stets bei Frequenzen im Bereich der steil abfallenden Flanke der Schwellenkurve fur Tone, namlich bei ungefahr 82.8 kHz (Abb. 8, 9). Die Schwellenmessungen fur Frequenzmodulationen sind mit entsprechenden Amplitudenmessungen der evoked potentials bei gleichbleibendem Schalldruck konsistent (Abb. 11). 6. Die kleinsten Sweepraten (Sweephohe/Sweepdauer), die noch eine evoked potential-Antwort auslosten, lagen fur Aufwartssweeps bei ungefahr 6 Hz/msec (Tabelle 1). Sweeprateu dieser Grosenordnung entstehen in der Beutefangsituation durch Flugelschlag von Insekten oder durch plotzliche Richtungsanderungen des Beutetieres aufgrund des Dopplereffektes. Der Echoortungslaut der Grosen Hufeisennase mit seinem langen konstantfrequenten Anteil und die hohe Empfindlichkeit ihres Horsystems gegenuber kleinen Sweepraten bilden ein System, das es der Grosen Hufeisennase erlaubt, solche beschleunigten Bewegungen besonders gut zu orten. 7. Fur Abwartssweeps der Sweephohe SH=1000 Hz treten in Abhangigkeit von der Ausgangsfrequenz der Frequenzmodulation im evoked potential Wellen verschiedener Polaritat auf. Die Frequenz 83.3 kHz ist dadurch ausgezeichnet, das unterhalb dieser Frequenz die negative Welle stark uberwiegt, oberhalb dieser Frequenz jedoch die positive Welle ausgepragt vorhanden ist (Abb. 12, 13). Die Grose Hufeisennase kann daher unterscheiden, ob die Ausgangsfrequenz des Endsweeps ihres Lautes im Echo ober- oder unterhalb von 83,3 kHz liegt. 83,3 kHz entspricht jedoch gerade der Frequenz, auf die die Grose Hufeisennase durch die Dopplereffektkompensation die Echofrequenz einreguliert.

The influence of blood flow and water net flux on the absorption of tritiated water from the jejunum of the rat.

Abstract: 1. Jejunal loops of anaesthetized rats were perfused with hypo-, iso-, and hypertonic buffered solutions containing tritiated water. The blood flow, the disapperance rate (from the intestinal lumen), and the appearance rate (in the intestinal venous blood) were determined simultaneously. 2. A decrease of the blood flow from about 1.7 to 0.2 ml min−1g−1 wet tissue weight diminished the appearance and disappearance rate of tritiated water. An increase of the blood flow caused the reversed results. The appearance rate was almost completely determined by the blood flow indicating that the intestinal absorption of tritiated water is blood flow limited. Therefore the absorption rate of tritiated water characterizes badly the diffusive water permeability of the intestinal epithelium. 3. A water net flux directed towards the blood accelerated and towards the intestinal lumen retarded the intestinal absorption of tritiated water at low, intermediate, and high blood flow values. 4. The data were analysed by a modified four-compartment-model considering the variation of blood flow and water net flux. The water net flux influences the absorption of tritiated water during the penetration through the epithelium by solvent drag (sieving coefficient 1-σ=1.54±0.19) as well as by changing the blood flow rate through capillaries near the epithelium.

Messung der K + - und Na + -Aktivität mit Mikro-Glaselektroden im Extracellulärraum des Kaninchenskeletmuskels bei Muskelarbeit

Abstract: Rabbits were anaesthetized with urethane and pentobarbitone sodium. The K+ and Na+ activity in the blood of the femoral vein or in the interstitial space of a skeletal muscle (vastus medialis of M. quadriceps femoris) were measured continuously by means of glass microelectrodes during stimulation of the muscles of the hindlimb. The blood flow in the femoral artery was recorded simultaneously by means of a Statham flowmeter. The K+ activity (at rest about 4 mmole/l) rose during the stimulation of the musculature. The course of the K+ increase was similar to that of the functional hyperemia. Maximum values obtained by frequent supramaximal stimulation (40 cps) were 6–6.5 mmole/l in the venous blood and 8–8.5 mmole/l in the interstitial space. The Na+ activity also rose from about 135 mmole/l to 136–140 mmole/l. The findings support the assumption that potassium shifts play a role in the regulation of functional hyperemia.

Perazine, chlorpromazine and imipramine as inducers of microsomal drug metabolism.

Abstract: Male rats were treated orally for 7 days with perazine, chlorpromazine, imipramine or phenobarbital. Isolated liver microsomes were tested for their metabolic activities towards perazine, ethylmorphine and aniline. N-Demethylation of perazine and ethylmorphine was increased 2–3.5 fold by all pretreatments. Aromatic hydroxylation of perazine was decreased in microsomes from pretreated animals, whereas aniline hydroxylation was enhanced even more by perazine and imipramine than by phenobarbital. The yield of perazine sulfoxide was increased by phenobarbital treatment only. Perazine N-oxide formation was reduced by treatment with psychoactive drugs to 75–90% of control values and by phenobarbital to less than 50%. The microsomal cytochrome P-450 concentration was slightly elevated by perazine and substantially by chlorpromazine and imipramine treatment. The tricyclic drugs investigated are potent inducers of the drug-metabolizing enzyme system, the induction pattern differing in some respects from that seen after phenobarbital.

Structure and function of the kidney in multiple myeloma.

Abstract: Morphological examinations of the kidneys of 146 plasmocytoma patients revealed the typical pathological-anatomical picture of myeloma kidney in only a third. In 23%, histological changes characteristic of acute renal failure were present and in a further 17% only evidences of acute renal failure were detected. In 8% the picture was dominated by severe pyelonephritis; nearly a third of all cases showed no morphological peculiarities. When correlated with clinical data it was noted that in renal insufficiency there was pathological evidence in 48% of myeloma kidney, in 36% evidence of acute renal failure. In about a third of all kidneys of plasmocytoma patients with renal insufficiency were there signs of acute renal failure. In only two patients could contracted kidneys be implicated as the cause of renal dysfunction.