Phenotypic instability in a tif-1 mutant of Escherichia coli

Summary A recent study showed that in E. coli T44 () carrying the tif-1 mutation, elevated temperature and adenine can interfere with the translation process. The present study shows that the expression of tif phenotypes (thermoinduction and filamentation) is suppressed by factors which affect ribosomal function. Ethanol suppresses thermoinduction and, in some spc ^r mutants, both thermoinduction and filamentation are suppressed. An unknown factor(s) in yeast extract suppresses both thermoinduction and filamentation. In thermoresistant revertant (ts⁺), the expression of the ts⁺ phenotype is suppressed by yeast extract, ethanol, guanosine+cytidine and by the addition of a spc ^r mutation. This indicates that this phenotype could be due to suppressor mutations, and the interaction between factors affecting ribosomal function and the ts⁺ phenotype suggests that the suppression of tif in the ts⁺ strains could operate on the ribosomal level. In vitro studies show that in extracts from either spc ^r or ts⁺ strains, or in the presence of ethanol, translational restriction is relieved, suggesting that the suppression of tif phenotypes could involve the translation process.     

Inhibition of cholesterol esterases by Δ1-tetrahydrocannabinol

Δ¹-Tetrahydrocannabinol was found to inhibit the action of esterases derived from rat adrenal and luteinized ovary on exogenous cholesteryl palmitate. The drug was effective at a dose of 3.2μM causing greater than 30% inhibition; at 16μM almost complete inhibition occured. These findings are similar to those we have recently reported with mouse Leydig cells (1) showing that this is an effect common to steroidogenic tissues and raising the possibility that a variety of endocrine effects of this drug may be due to direct action on these tissues.     

The role of transferrin and citrate in cellular uptake of aluminium

Summary The ability of human erythroleukaemia K562 cells to take up aluminium from Al-transferrin and Al-citrate has been examined. Uptake from Al-transferrin was dose-dependent over the range 68–544 ng/ml of aluminium, and increased over a 12-day period. In contrast, uptake from Al-citrate was low even at an aluminium concentration of 6800 ng/ml and did not increase over time. Neither form of aluminium greatly affected cell growth. It is concluded that Al-transferrin, rather than Al-citrate, is the physiologically relevant form of this metal with respect to cellular uptake, but that any metabolic abnormalities induced by aluminium do not affect proliferation of this cell line.     

Enhanced microvascular permeability of PMA-induced acute lung injury is not mediated by cyclooxygenase products.

Products of cyclooxygenase activity have been proposed to mediate the pulmonary hypertension and increased microvascular permeability associated with phorbol myristate acetate- (PMA) induced acute lung injury. Previously, we reported that thromboxane (Tx) does not mediate PMA-induced pulmonary hypertension in intact anesthetized dogs. In the present study, PMA was administered to isolated canine lungs perfused with autologous blood at constant flow to investigate a possible role for Tx in the PMA-induced increase in microvascular permeability. Changes in permeability were assessed by determining changes in the capillary filtration coefficient (Kfc). In lobes pretreated with papaverine to prevent PMA-induced increases in pulmonary vascular resistance, Kfc increased from a baseline value of 0.2 +/- 0.03 to 1.5 +/- 0.29 ml.min-1.cmH2O-1.100 g wet lobe wt-1 (P < 0.01) 30 min after PMA (5.8 x 10(-8) M, n = 10). Concomitantly, TxB2, the stable metabolite of TxA2, increased from 138 +/- 44 to 1,498 +/- 505 pg/ml (P < 0.05) in the blood. Both the selective Tx synthase inhibitor, OKY-046 (7 x 10(-4) M, n = 6), and the cyclooxygenase inhibitor, indomethacin (10(-4) M, n = 7), prevented the PMA-induced increase in TxB2, but neither compound attenuated the PMA-induced increase in Kfc. ONO-3708 (10(-6) M), a selective prostaglandin (PG) H2/TxA2 receptor antagonist, prevented the vasoconstriction resulting from administration of U-46619, a stable PGH2/TxA2 receptor agonist, but it did not prevent the PMA-induced increases in Kfc (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)     

Evolutionary significance of the renal excretion of transferrin half-molecule fragments

It is generally thought that the duplicated structure of serum transferrin in vertebrates arose by gene duplication and fusion from a small ancestral protein. We have found that the isolated domains of transferrin are rapidly lost from the bloodstream via the kidneys. Therefore we suggest that the ancestral transferrin was not a serum protein or, alternatively, that it was not as small as the half-molecule.     

Control of yeast cell type by the mating type locus: II. Genetic interactions between MATα and unlinked α-specific STE genes

The alleles of the yeast mating type locus, MATα and MATa, determine the yeast cell types, a,α, and a/α. It has been proposed that the MATα2 product negatively regulates expression of unlinked a-specific genes, and that the MATα1 product positively regulates expression of unlinked α-specific genes. The behavior of mutants defective in MATα2, which are deficient in mating and in production of α-factor, can thus be attributed to antagonism between a-specific and α-specific functions expressed simultaneously in matα2^? strains. If this view is correct, then elimination by mutation of the specific functions required to mate as α may allow matα2 mutants to mate as a. In order to test this possibility, we examined the interactions between matα2 mutations and various unlinked mutations that cause α cells but not a cells to be mating defective (α-specific STE mutations). Three α-specific mutations (ste3, ste13 and kex2) were found to be non-allelic. Furthermore, although matα2 mutants mate weakly as a, matα2, ste3 double mutants, but not matα2 ste13 or matα2 kex2 double mutants, mate efficiently as a. The ability of matα2 ste3 strains to mate as a supports the view that matα2 mutants express a-specific mating functions, and suggests that a mating functions are expressed constitutively in MATa cells. The mating behaviour of the matα2 ste3 double mutant is consistent with the proposal that STE3 is positively regulated by the MATα1 product.     

Evidence that calmodulin may be involved in phytohaemagglutinin-stimulated lymphocyte division

Phytohaemagglutinin-stimulated and non-stimulated incorporation of [³H]thymidine into human peripheral blood lymphocytes is inhibited by the calcium antagonist PY 108–068 and by the calmodulin antagonists trifluo-perazine andN-(6-aminohexyl)-5-chloro-l-naphthalene sulphonamide (W7). It is argued that calmodulin may be involved in both non-stimulated [³H]thymidine uptake in lymphocytes and also in the lymphocyte response to phytohaemagglutinin.