Chemotherapeutic effects of 4-isothiocyanato-4'-nitrodiphenylamine (C9333-Go/CGP 4540) on infections with Nematospiroides dubius, Hymenolepis diminuta, Hymenolepis nana and Spirometra mansonoides.

4-Isothiocyanato-4'-nitrodiphenylamine possessed anthelmintic activity against Nippostrongylus dubius and Hymenolepis nana in mice and H. diminuta in rats as determined by both egg counts and recovery of parasites at autopsy. No activity was detected against the cestode. Spirometra mansonoides, in cats.     

Bazooka recruits Inscuteable to orient asymmetric cell divisions in Drosophila neuroblasts

Asymmetric cell divisions can be generated by the segregation of determinants into one of the two daughter cells. In Drosophila, neuroblasts divide asymmetrically along the apical-basal axis shortly after their delamination from the neuroectodermal epithelium. Several proteins, including Numb and Miranda, segregate into the basal daughter cell and are needed for the determination of its correct cell fate. Both the apical-basal orientation of the mitotic spindle and the localization of Numb and Miranda to the basal cell cortex are directed by Inscuteable, a protein that localizes to the apical cell cortex before and during neuroblast mitosis. Here we show that the apical localizaton of Inscuteable requires Bazooka, a protein containing a PDZ domain that is essential for apical-basal polarity in epithelial cells. Bazooka localizes with Inscuteable in neuroblasts and binds to the Inscuteable localization domain in vitro and in vivo. In embryos lacking both maternal and zygotic bazooka function, Inscuteable no longer localizes asymmetrically in neuroblasts and is instead uniformly distributed in the cytoplasm. Mitotic spindles in neuroblasts are misoriented in these embryos, and the proteins Numb and Miranda fail to localize asymmetrically in metaphase. Our results suggest that direct binding to Bazooka mediates the asymmetric localization of Inscuteable and connects the asymmetric division of neuroblasts to the axis of epithelial apical-basal polarity.     

Boron and oxygen isotope evidence for recycling of subducted components over the past 2.5 Gyr

Evidence for the deep recycling of surficial materials through the Earth's mantle and their antiquity has long been sought to understand the role of subducting plates and plumes in mantle convection. Radiogenic isotope evidence for such recycling remains equivocal because the age and location of parent-daughter fractionation are not known. Conversely, while stable isotopes can provide irrefutable evidence for low-temperature fractionation, their range in most unaltered oceanic basalts is limited and the age of any variation is unconstrained. Here we show that delta(18)O ratios in basalts from the Azores are often lower than in pristine mantle. This, combined with increased Nb/B ratios and a large range in delta(11)B ratios, provides compelling evidence for the recycling of materials that had undergone fractionation near the Earth's surface. Moreover, delta(11)B is negatively correlated with (187)Os/(188)Os ratios, which extend to subchondritic values, constraining the age of the high Nb/B, (11)B-enriched endmember to be more than 2.5 billion years (Gyr) old. We infer this component to be melt- and fluid-depleted lithospheric mantle from a subducted oceanic plate, whereas other Azores basalts contain a contribution from approximately 3-Gyr-old melt-enriched basalt. We conclude that both components are most probably derived from an Archaean oceanic plate that was subducted, arguably into the deep mantle, where it was stored until thermal buoyancy caused it to rise beneath the Azores islands approximately 3 Gyr later.     

Changes in intracellular pH and cell volume during the early phase of DMSO-induced differentiation of friend erythroleukemia cells

Summary Changes in intracellular pH and water volume were measured after treatment of Friend erythroleukemia cells with 1.5% DMSO. It was found that a continuous decrease in pH_i occurred, beginning 1 h after induction and a decline in pH_i of 0.18 was measured after 9 h. In addition a decline in cellular water volume, of 12% only 15 min after induction, and 23% after 9 h, was observed.11 December 1986Acknowlegments. This work was supported by the Deutsche Forschungsgemeinschaft.     

Effects of CO2 exposure on distribution of various forms of iron and copper in guinea-pig tissues

The effects on iron and copper distribution and metabolism of exposure to high levels of CO2 were studied in the guinea-pig. Mature, male animals were placed in an atmosphere of 15% CO2, 21% O2 (balance N2), and sacrificed from 1 h to 1 week thereafter. Total iron and copper concentrations of blood, liver, spleen and bone, as well as concentrations of heme and ferritin iron, were measured together with blood hematocrit, reticulocytes, plasma hemoglobin, plasma ceruloplasmin and copper concentrations. The results show clearly that rapid and sustained red cell damage or hemolysis ensued several h from the start of CO2 treatment. This resulted in loss of iron and copper from the blood, an influx of both elements into liver, spleen and bone, and a rise in plasma ceruloplasmin. Influx of iron into liver and spleen caused an accumulation of ferritin, the main site for iron storage in cells. Following the effect on red cells, there was an accumulation of heme iron, and a decreased hematocrit, best explained by a depressed activity of the reticuloendothelial and erythropoietic systems. A period of adaptation succeeded these events, in which all blood parameters and most tissue values returned to normal, despite the continuing presence of high CO2. The only changes not reversed were the elevations in liver, spleen and bone iron stores. These remained high, with a net accumulation of greater than 2 mg iron, or 3-4 times more than originally present. The results indicate that at least in the guinea-pig, high CO2 exposure results in red cell damage and other events leading to an accumulation of additional iron in the body; also, that iron accumulated as ferritin and hemosiderin in liver and spleen may not be readily available to restore blood hemoglobin concentrations on an acute basis.