Interferon-beta can induce the production of plasminogen activator by cultured human cancer cells

Three cultured human cell lines, renal cancer cells (ACHN), bladder cancer cells (EJ), and fibroblasts transformed in culture by Co-60 gamma rays (KMST-6), when treated with interferon-beta, produced 1.5 to 4 times as much plasminogen activator as the untreated control cultures. This enhanced production of PA was inhibited by cycloheximide or actinomycin D.     

On the mechanism of pyrogenic action of ricin

Summary The incubation of rabbit white blood cells with ricin, the toxic protein of castor oil seeds, leads to the production of endogenous pyrogens. This induction can be inhibited by the antibiotics actinomycin D or cycloheximide. The results are discussed in terms of disturbed corticosteroid- and Mg²⁺-levels.Acknowledgments. The author is very grateful to the Uganda National Research Council for the Research Grant No. 60.660.00 (through Makerere University, Kampala) without which the completion of his inaugurated Ph. D. Thesis would not have been possible. This paper represents a part of this Thesis.     

The phorbol ester TPA induces metamorphosis in Red Sea coral planulae (Cnidaria: Anthozoa)

Controlled experiments on the metamorphosis of marine invertebrate larvae require artificial inducers. These inducers can be used for studying the involvement of known signal transduction pathways in settlement and metamorphosis. The ability of the tumor-promoting phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate) to induce metamorphosis in planulae of the Red Sea soft coral speciesHeteroxenia fuscescens, Xenia umbellata, Dendronephthya hemprichii, Litophyton arboreum andParerythropodium fulvum fulvum, and the stony coralStylophora pistillata, was examined by using various concentrations of TPA. The chemical induced metamorphosis in all six species. The effect was unspecific and concentration-related. For all the corals except forX. umbellata the highest mean percentages of metamorphosis were obtained with 8.1×10^–7–10^–9 M TPA. ForX. umbellata, the percentage of metamorphosis was lower, and was obtained within a wider TPA concentration range. The present results, along with previous studies on Hydrozoa and Scyphozoa, demonstrate that TPA is the first common artificial inducer for these classes of Cnidaria. TPA is known to activate the enzyme protein kinase C (PKC) and therefore plays an important role in studying the phosphatidylinositol signal transduction system. Evidence for the involvement of this pathway in triggering metamorphosis has already been reported for Hydrozoa and Scyphozoa. Our results suggest that PKC is also involved in initiating metamorphosis in Anthozoa.     

The effect of cycloheximide on nuclear uH2A content

Summary The effect of intraperitonal cycloheximide administration on acid-soluble rat liver chromatin proteins has been investigated by electrophoresis in acetic acid-urea polyacrylamide gels. A nonhistone protein, which migrates between oxidized histone H3 and histone H1 has been found tobe increased in amount following cycloheximide treatment. This protein seems to be identical with semihistone protein H24 (uH2A). A possible relationship of uH2A to the inhibition of rRNA synthesis is discussed.This work was supported by the Turkish Scientific and Technical Research Council (TUBITAK) Project No. TAG 339     

Uninterrupted protein synthesis is essential for survival in the early stages of carbon tetrachloride-induced hepatocellular necrosis in the mouse

The fatal syndrome produced by cycloheximide given 6 h after a hepatonecrogenic dose of CCl4 is due neither to direct toxic synergism between CCl4 and cycloheximide nor to transient sinusoidal thrombosis. It is suggested that survival in the presence of unknown factors released from dying liver cells requires uninterrupted protein synthesis. The life-saving effect of sterilization of the intestine by antibiotics indicates that the gut flora or its products play a vital role in pathogenesis.     

Interferon-β can induce the production of plasminogen activator by cultured human cancer cells

Summary Three cultured human cell lines, renal cancer cells (ACHN), bladder cancer cells (EJ), and fibroblasts transformed in culture by Co-60 gamma rays (KMST-6), when treated with interferon-, produced 1.5 to 4 times as much plasminogen activator as the untreated control cultures. This enhanced production of PA was inhibited by cycloheximide or actinomycin D.     

Endogenous pyrogen formation by human blood monocytes stimulated by polyriboinosinic acid:Polyribocytidylic acid

The pyrogenic response to supernatants from human blood monocytes stimulated with polyriboinosinic acid:polyribocytidylic acid (poly I:C) was characteristic of a response to endogenous pyrogen in that it was brief and monophasic, and was destroyed by heating the supernatants at 70°C for 30 min. Pyrogen production was unimpaired when the incubations were carried out in the presence of cycloheximide (50 g/ml; an inhibitor of protein synthesis) or indomethacin (50 g/ml; an inhibitor of prostaglandin synthesis). Also, neither interferon, interleukins, tumor necrosis factor nor prostaglandin E₂ were detectable in the supernatants from the poly I:C-stimulated human monocytes.     

Control of the behaviour of leaf-cutting ants by their ‘symbiotic’ fungus

There is an obligatory relationship between leaf-cutting ants of the generaAtta andAcromyrmex (Hymenoptera; Attini) and the fungus,Attamyces bromatificus Kreisel, for which they provide a substrate of cut plant material. We show that the ants learn to reject plant material that contains chemicals injurious to the fungus. After an initial period of acceptance, ants from laboratory nests stopped harvesting granular bait containing a fungicidal agent (cycloheximide) and orange peel. This rejection was maintained for many weeks. These colonies also rejected control bait containing no cycloheximide. Some generalisation of the response was observed; colonies rejecting orange granules also rejected grapefruit granules, although they still accepted blackcurrant granules. Rejection of fungicidal bait by colonies in the field was restricted to ants on foraging trails exposed to experimental bait. We conclude that a semiochemical from the fungus, circulated by trophallaxis and grooming, regulates the selection of plant material by foragers. The fungus gains more advantages from the symbiotic relationship than is often realised. The ants provide the fungus with housing, sanitation, defence against disease and predators, pre-selected food, and a means of dissemination, at the cost to itself of providing food for the ant brood.     

The effect of cycloheximide on nuclear uH2A content

The effect of intraperitonal cycloheximide administration on acid-soluble rat liver chromatin proteins has been investigated by electrophoresis in acetic acid-urea polyacrylamide gels. A nonhistone protein, which migrates between oxidized histone H3 and histone H1 has been found to be increased in amount following cycloheximide treatment. This protein seems to be identical with semihistone protein H24 (uH2A). A possible relationship of uH2A to the inhibition of rRNA synthesis is discussed.     

Uninterrupted protein synthesis is essential for survival in the early stages of carbontetrachloride-induced hepatocellular necrosis in the mouse

Summary The fatal syndrome produced by cycloheximide given 6 h after a hepatonecrogenic dose of CCl₄ is due neither to direct toxic synergism between CCl₄ and cycloheximide nor to transient sinusoidal thrombosis. It is suggested that survival in the presence of unknown factors released from dying liver cells requires uninterrupted protein synthesis. The life-saving effect of sterilization of the intestine by antibiotics indicates that the gut flora or its products play a vital role in pathogenesis.Acknowledgments. I wish to thank Mr C. R. West for carrying out the statistical analysis, Mrs Brenda Brooks for histological processing, and Berk Pharmaceuticals Ltd for information on Ancrod defibrination in mice.     

Variations of testosterone uptake by gonadotropic cells of the adenohypophysis of the rat

Testosterone (T) could be detected by immunocytochemistry after cryoultramicrotomy and T is likely bound on a binding site of a high affinity. Castration and adrenalectomy involve a swift disappearance of T in the gonadotropic cells. Synthesis of new binding sites was induced by daily T injection in the castrated and surrenalectomized Rat from 90 days. This synthesis is inhibited by cycloheximide. These data suggest that binding sites are proteins. The captation of T by the gonadotropic cells was diminished similarly at the diminution of T, afterwards, T captation was stabilized at a weak level which became stable for several weeks. It seems that immunocytochemistry permits the study of the variation of T captation by Rat pituitary gonadotropic cells.     

Glucose-evoked recovery of hepatic thyroxine 5'-deiodinase independent of de novo protein synthesis in fasted rat

The glucose-evoked recovery of Type I thyroxine 5'-deiodinase activity in the hepatic microsomes of fasted rat was not inhibited by either cycloheximide, puromycin or actinomycin D during 3 h after glucose feeding; however, [3H]-leucine uptake by the liver or the hepatic microsomal fraction was significantly inhibited by cycloheximide and puromycin but not by actinomycin D. These results indicate that the glucose-evoked recovery of deiodinase activity may be independent of de novo protein synthesis.     

Pentagastrin induction of acetylcholinesterase activity in cerebral cortex of rats

Summary A single injection of pentagastrin (500 g kg^–1) produced an immediate (within 15 min) and pronounced increment (about 50%) in the activity of acetylcholinesterase (AChE) in the cerebral but not in the cerebellar region of the brain. Pretreatment of rats with either actinomycin-D or cycloheximide did not fully abolish the pentagastrin-mediated stimulation of cerebral AChE activity.Acknowledgments. A.M. Nakhla is recipient of a postdoctoral research fellowship from Danida, Ministry of Foreign Affairs, Denmark. The project was in part supported by grants to A.P.N.M. from The Laegevidenskabelige Forskningsråd and Danida, Denmark.     

Glucose-evoked recovery of hepatic thyroxine 5′-deiodinase independent of de novo protein synthesis in fasted rat

Summary The glucose-evoked recovery of Type I thyroxine 5-deiodinase activity in the hepatic microsomes of fasted rat was not inhibited by either cycloheximide, puromycin or actinomycin D during 3 h after glucose feeding; however, [³H]-leucine uptake by the liver or the hepatic microsomal fraction was significantly inhibited by cycloheximide and puromycin but not by actinomycin D. These results indicate that the glucose-evoked recovery of deiodinase activity may be independent of de novo protein synthesis.     

Reaction step requiring protein synthesis in DNA synthesis in sea urchin embryos

Summary In the acid-soluble fraction extracted from embryos treated with cycloheximide, thymidine triphosphate was largely accumulated and DNA polymerase activity decreased, while both activities of thymidine kinase and thymidylate kinase remained unchanged.     

Effects of cycloheximide on protein synthesis in human lung tumors, regenerating rat liver and hepatomas

10(-4) M cycloheximide (CHM) inhibits leucine incorporation to about the same degree in slices of human lung tumors, rat hepatomas, regenerating livers and normal tissues. At 10(-6) M, CHM has a more pronounced effect on tumor tissue and regenerating liver than on normal tissues. 10(-8) M CHM stimulates protein synthesis in normal rat liver slices.     

Molecular forms of dopamine beta-hydroxylase in rat superior cervical ganglion and adrenal gland

Summary Dopamine beta-hydroxylase (DBH) enzyme activity was associated in rat superior cervical ganglion with tetrameric DBH-A (294,000 D) and dimeric DBH-B (147,000 D) and in rat adrenal gland with DBH-A and a novel molecular form of DBH, defined as DBH-C, with a molecular weight of 125,000 D. Pretreatment of the rats with cycloheximide markedly reduced DBH activity without altering the molecular heterogeneity.     

Molecular forms of dopamine beta-hydroxylase in rat superior cervical ganglion and adrenal gland

Dopamine beta-hydroxylase (DBH) enzyme activity was associated in rat superior cervical ganglion with tetrameric DBH-A (294,000 D) and dimeric DBH-B (147,000 D) and in rat adrenal gland with DBH-A and a novel molecular form of DBH, defined as DBH-C, with a molecular weight of 125,000 D. Pretreatment of the rats with cycloheximide markedly reduced DBH activity without altering the molecular heterogeneity.