Therapy for acute myeloid leukemia in 119 adults: a comparison of two treatment protocols

Of 119 patients with acute myeloid leukemia, 69 were treated with Adriamycin, Vincristine and Cytosine Arabinoside (Therapy 1) and 50 with Daunorubicin, Cytosine Arabinoside and 6-Thioguanine (Therapy 2) as well as a consolidation therapy. The maintenance therapy with Cytosine Arabinoside and 6-Thioguanine was the same for both groups. The complete remission rate was 44% for Therapy 1 and 68% for Therapy 2 (p less than 0.05). - The median values for remission duration were 7 and 13 months respectively (p = 0.10); for survival time the median values were 18 and 19 months. These figures show in retrospect that high remission rates can be attained through intensive induction therapy and that longer remission duration is correlated with more aggressive induction therapy. A mild form of maintenance therapy seems to have little effect on the duration of complete remission.     

The influence of water on CO2 exchange in the lichen Parmelia praesignis Nyl.

Net photosynthetic rates for the lichen Parmelia praesignis Nyl. were obtained as a function of 5 light levels, 5 temperature levels, and of water content as thalli dried from saturated conditions. Data are described as second order polynomials in the light, and as saturation curves in the dark. Rates in the light were depressed at high water contents reaching maximal rates between 110% and 180% water content and declining as thalli dried. Physiological parameters were derived from the drying curves to investigate temperature and light interactions. Dark respiration parameters are the maximal rate, the water content where the rate is half-maximal, the water content at which respiration is zero, and the maximal water efficiency. In the light, parameters are the maximal net photosynthetic rate, the water content at the maximal rate, the water compensation point, the maximal water efficiency, and the sensitivity of net photosynthesis to change in water content.Values of half-maximal rate water contents for respiration were found to increase as temperatures increased. The greatest maximal net photosynthetic rate occurred at higher temperatures as the light intensity increased. In the light, maximal water efficiency and the sensitivity to changes in water content were generally maximal at temperatures yielding the greatest maximal net photosynthetic rates.     

Organization and function of cytochromeb and ubiquinone in the cristae membrane of beef heart mitochondria

The arrangement and function of the redox centers of the mammalianbc ₁ complex is described on the basis of structural data derived from amino acid sequence studies and secondary structure predictions and on the basis of functional studies (i.e., EPR data, inhibitor studies, and kinetic experiments). Two ubiquinone reaction centers do exist—a QH₂ oxidation center situated at the outer, cytosolic surface of the cristae membrane (Q₀ center), and a Q reduction center (Q _i center) situated more to the inner surface of the cristae membrane. The Q₀ center is formed by theb-566 domain of cytochromeb, the FeS protein, and maybe an additional small subunit, whereas the Q _i center is formed by theb-562 domain of cytochromeb and presumably the 13.4kDa protein (QP-C). The Q binding proteins are proposed to be protein subunits of the Q reaction centers of various multiprotein complexes. The path of electron flow branches at the Q₀ center, half of the electrons flowing via the high-potential cytochrome chain to oxygen and half of the electrons cycling back into the Q pool via the cytochromeb path connecting the two Q reaction centers. During oxidation of QH₂, 2H⁺ are released to the cytosolic space and during reduction of Q, 2H⁺ are taken up from the matrix side, resulting in a net transport across the membrane of 2H⁺ per e^– flown from QH₂ to cytochromec, the H⁺ being transported across the membrane as H (H⁺ + e^–) by the mobile carrier Q. The authors correct their earlier view of cytochromeb functioning as a H⁺ pump, proposing that the redox-linkedpK changes of the acidic groups of cytochromeb are involved in the protonation/deprotonation processes taking place during the reduction and oxidation of Q. The reviewers stress that cytochromeb is in equilibrium with the Q pool via the Q _i center, but not via the Q₀ center. Their view of the mechanisms taking place at the reductase is a Q cycle linked to a Q-pool where cytochromeb is acting as an electron pump.     

Kinetic comparison of bovine blood coagulation factors IXa alpha and IXa beta toward bovine factor X

The Vmax/Km (microM -1 min -1.) for bovine factor X activation by bovine factor IXa alpha, in the presence of sufficient [Ca2+] to saturate the initial reaction rate, was 0.007. When factor IXa beta was substituted for factor IXa alpha in this reaction, the Vmax/Km decreased to 0.001, suggesting that factor IXa alpha was a more potent catalyst under these conditions. When phospholipid (PL) vesicles (egg phosphatidylcholine/bovine brain phosphatidylserine, 4:1 w/w) were added to these same systems, at levels sufficient to saturate their effects, little change in the Vmax/Km occurred when factor IXa alpha was the enzyme. However, when factor IXa beta was employed, the Vmax/Km dramatically increased to 0.023, demonstrating that factor IXa beta responded to PL addition to a much greater extent than did factor IXa alpha. Upon addition of thrombin-activated factor VIII (factor VIIIa,t), at a suboptimal level, to the above systems, the Vmax/Km for factor X activation by factor IXa alpha/Ca2+/PL/factor VIIIa,t was increased to 1.0, whereas this parameter for factor X activation by factor IXa beta/Ca2+/PL/factor VIIIa,t under the same conditions was found to be 27.3. During these studies, it was discovered that the factor X which became activated to factor Xa during the course of reaction participated in several feedback reactions: activation of factor X, activation of factor VIII, and conversion of factor IXa alpha to factor IXa beta. All feedback reactions, which are capable of complicating the kinetic interpretation, were inhibited by performing the studies in a system which contained a rapid factor Xa inhibitor, Glu-Gly-Arg-CH2Cl, thus allowing kinetic constants to be accurately determined. The results show that while factor IXa alpha is a more efficient enzyme than factor IXa beta toward factor X activation in the absence of cofactors, the response of factor IXa beta to the reaction cofactors, PL and factor VIIIa,t, is much greater than that of factor IXa alpha.     

Indolderivate im Apfel

Zusammenfassung Zur Identifizierung der Streckungswuchsstoffe in Apfelgeweben wurden Extrakte aus vegetativen und reproduktiven Organen in verschiedenen Entwicklungsstadien chromatographiert und mit Hilfe des Weizen-Koleoptilzylinder-Tests, verschiedener Farbreagentien und synthetischer Vergleichssubstanzen auf ihre Wuchsstoffwirkung und ihren Gehalt an Indolderivaten geprüft. Alle untersuchten Gewebe ergaben im biologischen Test dieselben Wuchsstoffe, allerdings mit erheblichen quantitativen Unterschieden.In der sauren Fraktion von Ätherextrakten aus dem Fruchtfleisch verschiedener Apfelsorten ließen sich Malonyltryptophan, Indol-3-carbonsäure, 2-Hydroxy-indol-3-essigsäure, Indol-3-essigsäure, Indol-3-aldehyd (vor allem in reifen Früchten) und Indol-3-essigsäure-äthylester (in unreifen Früchten) identifizieren. In Gegenwart von IES trat häufig auch Indol-3-acetamid auf; dieses, die Indol-3-essigsäure und 2-Hydroxy-indol-3-essigsäure und der Indol-3-essigsäure-äthylester zeigten im Weizen-Koleoptilzylinder-Test Wuchsstoffwirkung.Nach Hydrolyse des mit Äther extrahierten Materials fanden sich neben einer größeren Anzahl unbekannter Substanzen, die im Farb-Test Indolreaktionen ergaben, drei weitere, im biologischen Test aktive Indolderivate, von denen das eine als Indol-3-acetylasparaginsäure identifiziert werden konnte; die anderen beiden sind möglicherweise ebenfalls Verbindungen der IES mit Aminosäuren.Im Weizen-Koleoptilzylinder-Test konnte eine Überlagerung der Indolderivate mit unbekannten, ebenfalls aktiven Substanzen nicht ausgeschlossen werden.Mit 3 Textabbildungen     

Protein- und RNS-Gehalt des Hypokotyls beim stationären Wachstum im Dunkeln und unter dem Einfluß von Phytochrom (Keimlinge von Sinapis alba L.)

Zusammenfassung Das Wachstum des Hypokotyls wurde an Restkeimlingen ohne Kotyledonen (Abb. 1) untersucht. Die Wachstumsgeschwindigkeit ist in dem von uns untersuchten Zeitraum sowohl im Dunkeln als auch unter dem Einfluß von P₇₃₀ (Dauer-Dunkelrot) praktisch konstant. Obgleich sich die Wachstumsgeschwindigkeiten im Dunkeln und im Dauer-Dunkelrot um den Faktor 4 unterscheiden, hat das Dunkelrot keinen signifikanten Einfluß auf den Gesamt-Proteingehalt des Hypokotyls (bzw. der durchschnittlichen Hypokotylzelle). Der Proteingehalt nimmt im Dunkeln und im Licht kontinuierlich ab. Auch der Gesamt-RNS-Gehalt zeigt innerhalb des Versuchszeitraums eine Abnahme, die unter dem Einfluß von Dunkelrot früher einsetzt als im Dunkeln. — Man kann aus den Daten der vorliegenden Arbeit schließen, daß nur ein kleiner Teil des Gesamt-Proteins und der Gesamt-RNS einer Zelle mit dem Zellwachstum unmittelbar in Verbindung gebracht werden kann.

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Protein and RNA contents of the hypocotyl during steady state growth lengthening in the dark and under the influence of phytochrome (seedlings of sinapis alba L.)

Summary Inhibition of hypocotyl lengthening by phytochrome can be regarded as a prototype of a negative photoresponse. The hypothesis has been advanced (Schopfer, 1967) that negative photoresponses are the consequence of a differential gene repression which is exerted by P₇₃₀, the active phytochrome. This hypothesis is mainly based on experiments with specific inhibitors of RNA- and protein synthesis. —The present paper is part of an experimental program which has been designed to check this hypothesis.—Continuous irradiation with standard far-red has been used to establish a virtually stationary concentration of P₇₃₀ over the whole period of experimentation (36–60 hours after sowing). To correlate more strictly the growth response of the hypocotyl with molecular changes in this organ the axis system without cotyledons has been used (Fig. 1). Even under these conditions the growth rate of the hypocotyl is nearly constant in light (continuous far-red) and dark during the whole period of experimentation (36–60 hours after sowing) (Fig. 2, 3). It is known from earlier experiments that cell division in the hypocotyl are very rare during this period and that there is virtually no increase in the DNA contents of the organ during the period of our experimentation (Weidner, 1967). Obviously the number of cells per hypocotyl is virtually constant between 36 and 60 hours after sowing. Organ (i.e. hypocotyl) lengthening is nearly exclusively due to cellular lengthening.—If we follow the protein contents of the hypocotyl we find (Fig. 4) that the total protein of the organ decreases steadily in spite of the fact that the organ grows at a constant rate. There is no significant difference in protein contents between dark-grown and far-red grown systems although the growth rates differ by a factor of 4 (Fig. 2, 3).—The situation is some-what different with respect to total RNA (Fig. 5). The RNA contents eventually decrease in far-red as well as in dark-grown systems but the decrease is significantly faster in the far-red treated systems than in the dark controls.—It is concluded that only a very small part of the total RNA and total protein of a cell can be related to the control of cellular growth. Changes in bulk RNA and bulk protein obviously do not necessarily reflect changes in the growth rate or growth capacity of an organ or a cell.

     

Amplification of small signals by voltage-gated sodium channels in drone photoreceptors

Summary Photoreceptor cells of the drone,Apismellifera , have a voltage-gated Na⁺ membrane conductance that can be blocked by tetrodotoxin (TTX) and generates an action potential on abrupt depolarization: an action potential is triggered by the rising phase of a receptor potential evoked by an intense light flash (Autrum and von Zwehl 1964; Baumann 1968). We measured the intracellular voltage response to a small (9%), brief (30 ms) decrease in light intensity from a background, and found that its amplitude was decreased by 1M TTX. The response amplitude was maximal when the background intensity depolarized the cell to –38 mV. With intensities depolarizing the cell membrane to –45 to –33 mV the average response amplitude was decreased by TTX from 1.2mV to 0.5mV. TTX is also known to decrease the voltage noise during steady illumination (Ferraro et al. 1983) but, despite this, the ratio of peak-to-peak signal to noise was, on average, decreased by TTX. The results suggest that drone photoreceptors use voltage-gated Na⁺ channels for graded amplification of responses to small, rapid changes in light intensity.Abbreviations TTX tetrodotoxin - V _i intracellular potential with respect to the bath - V _o extracellular potential - V _m,V _i-V _o approximate transmembrane potential - S amplitude of the voltage response to an 8.9% decrease in light intensity - N voltage noise, usually measured as root mean square voltage deviation as described in Methods     

The effect of endogenous and externally supplied nitrate on nitrate uptake and reduction in sugarbeet seedlings

The pericarp of the dormant sugarbeet fruit acts as a storage reservoir for nitrate, ammonium and -amino-N. These N-reserves enable an autonomous development of the seedling for 8–10 d after imbibition. The nitrate content of the seed (1% of the whole fruit) probably induces nitrate-reductase activity in the embryo enclosed in the pericarp. Nitrate that leaks out of the pericarp is reabsorbed by the emerging radicle. Seedlings germinated from seeds (pericarp was removed) without external N-supply are able to take up nitrate immediately upon exposure via a low-capacity uptake system (v_max = 0.8 mol NO ₃ ^- ·(g root FW)^–1·h^–1; K_s = 0.12 mM). We assume that this uptake system is induced by the seed nitrate (10 nmol/seed) during germination. Induction of a high-capacity nitrate-uptake system (v_max = 3.4 mol NO ₃ ^- ·(g root FW)^–1·h^–1; K_s = 0.08 mM) by externally supplied nitrate occurs after a 20-min lag and requires protein synthesis. Seedlings germinated from whole fruits absorb nitrate via a highcapacity uptake mechanism induced by the pericarp nitrate (748 nmol/pericarp) during germination. The uptake rates of the high-capacity system depend only on the actual nitrate concentration of the uptake medium and not on prior nitrate pretreatments. Nitrate deprivation results in a decline of the nitrate-uptake capacity (t_1/2 of v_max = 5 d) probably caused by the decay of carrier molecules. Small differences in K_s but significant differences in v_max indicate that the low- and high-capacity nitrate-uptake systems differ only in the number of identical carrier molecules.Abbreviations NR nitrate reductase - pFPA para-fluorophenylalanine This work was supported by a grant from Bundesministerium für Forschung und Technologie and by Kleinwanzlebener Saatzucht AG, Einbeck.