Steady-state kinetic studies with the polysulfonate U-9843, an HIV reverse transcriptase inhibitor

The tetramer of ethylenesulfonic acid (U-9843) is a potent inhibitor of HIV-1 RT^* and possesses excellent antiviral activity at nontoxic doses in HIV-1 infected lymphocytes grown in tissue culture. Kinetic studies of the HIV-1 RT-catalyzed RNA-directed DNA polymerase activity were carried out in order to determine if the inhibitor interacts with the template: primer or the deoxyribonucleotide triphosphate (dNTP) binding sites of the polymerase. Michaelis-Menten kinetics, which are based on the establishment of a rapid equilibrium between the enzyme and its substrates, proved inadequate for the analysis of the experimental data. The data were thus analyzed using steady-state Briggs-Haldane kinetics assuming that the template:primer binds to the enzyme first, followed by the binding of the dNTP and that the polymerase is a processive enzyme. Based on these assumptions, a velocity equation was derived which allows the calculation of all the specific forward and backward rate constants for the reactions occurring between the enzyme, its substrates and the inhibitor. The calculated rate constants are in agreement with this model and the results indicated that U-9843 acts as a noncompetitive inhibitor with respect to both the template:primer and dNTP binding sites. Hence, U-9843 exhibits the same binding affinity for the free enzyme as for the enzyme-substrate complexes and must inhibit the RT polymerase by interacting with a site distinct from the substrate binding sites. Thus, U-9843 appears to impair an event occurring after the formation of the enzyme-substrate complexes, which involves either an event leading up to the formation of the phosphoester bond, the formation of the ester bond itself or translocation of the enzyme relative to its template:primer following the formation of the ester bond.     

Ecdysteroids: possible candidates for the hormone which triggers salivary gland degeneration in the ixodid tickAmblyomma hebraeum

Summary Following engorgement, female ixodid ticks secrete a tick salivary gland degeneration factor (TSGDF) into the hemolymph. Here we show that the arthropod ecdysteroid hormones, ecdysome and 20-hydroxyecdysone, induce degeneration of tick salivary glands maintained in organ culture. The effective dose range in vitro is 30–300 ng/ml, a range reported to be physiological for this species following repletion. In addition, infusion of 20-hydroxyecdysome in vivo induces salivary gland degeneration. We therefore propose that TSGDF may be an ecdysteroid.Acknowledgments. Some of the data reported here were presented to the annual meeting of the Canadian Society of Zoologists, 15–18 May 1983; Program of abstracts, page 53. Financial support of the Canadian National Sportsmen's Fund and NSERC Canada to W.R.K. is gratefully acknowledged.     

Vasoactive intestinal polypeptide stimulates prolactin release in vivo in the ring dove (Streptopelia risoria)

Summary I.v. administration of vasoactive intestinal polypeptide (VIP) to ring doves significantly elevated the plasma concentration of prolactin after 10 min in a dose-related manner. The plasma prolactin concentration of nonbreeding doves with low basal levels was increased by a similar amount as in brooding doves whose initially high concentration of plasma prolactin had been reduced by nest deprivation prior to treatment.     

Untersuchungen über den Wirkungsmechanismus von Procarbazin (Natulan®)

Summary The cytotoxic methylhydrazine derivative procarbazine or Natulan® has a marked influence on the synthesis of deoxyribonucleic acid in Ehrlich ascites carcinoma cells. The incorporation of³H-thymidine into DNA — measured by autoradiographic methods — is inhibited.     

Temperature and mutant expression

Zusammenfassung Durch Versuche mit der Mutante ci^D von Drosophila wurde nachgewiesen, dass die temperaturabhängigen Veränderungen in der Ausprägungsweise ausschliesslich durch den Restgenotypus bestimmt werden. Diese Feststellung hat Bedeutung für Genphysiologie, Evolution und quantitative Vererbung.

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I should like to thank Prof.H. Gloor for his critical interest and Prof.H. R. van der Vaart of the Instituut voor Theoretische Biologie, Leiden, for advice in statistical matters.     

Dosis-Wirkungs-Beziehungen zwischen Koronardurchfluss und Herzfrequenz für Adenosin

Summary In the isolated guinea-pig heart, it has been found that the amount of adenosine which slows the heart rate is about 100 times greater than the amount which increases coronary flow.     

Auslösende Faktoren beim Duftmarkieren von Sammelbienen

Summary Scent marking behaviour (exposure of the Nasonov gland) of foraging honeybees (Apis mellifica) depends on the flux of sugar per unit-time in the food source.