α-Adrenoceptor blocking action of hymenin,a novel marine alkaloid

Summary In the rabbit isolated aorta, hymenin (10^–6 M) a novel marine alkaloid, caused a parallel rightward shift of the dose-response curve for norepinephrine without affecting that for histamine or KCl, suggesting that hymenin is a competitive antagonist of -adrenoceptors in vascular smooth muscles.Acknowledgments. We thank Ms A. Kajiwara and Ms M. Hamashima of this institute for their technical assistance, and Prof. Y. Hirata of Meijo University for his encouragement.     

9-α-hydroxyparthenolide,a novel antitumor sesquiterpene lactone fromAnvillea garcini (Burm.) DC1

Summary A novel sesquiterpene lactone, 9--hydroxyparthenolide (1) was isolated from a chloroform extract ofAnvillea garcini that was collected in Iran. The structure of1 was assigned on the basis of high field NMR decoupling experiments and other spectroscopic evidence. This -methylene lactone has shown significant activity in both the 9KB cell culture and P388 mouse leukemia test systems.The authors acknowledge the support of contract No. N01-CM-97296 from the National Cancer Institute and the use of the Purdue University Biochemical Magnetic Resonance Laboratory (NIH grant No. RR01077). This is paper 16 in the series Potential Antitumor Agents.     

α-Endosulfine, a new entity in the control of insulin secretion

ATP-dependent potassium (K_ATP) channels occupy a key position in the control of insulin release from the pancreatic β cell since they couple cell polarity to metabolism. These channels close when more ATP is produced via glucose metabolism. They are also controlled by sulfonylureas, a class of drugs used in type 2 diabetic patients for triggering insulin secretion from β cells that have lost part of their sensitivity to glucose. We have demonstrated the existence of endogenous counterparts to sulfonylureas which we have called ‘endosulfines.’ In this review, we describe the discovery, isolation, cloning, and biological features of the high-molecular-mass form, α-endosulfine, and discuss its possible role in the physiology of the β cell as well as in pathology. Received 1 February 1999; received after revision 26 March 1999; accepted 26 March 1999     

Chemistry of mediterranean gorgonians. II. Pregna 4,20-dien-11α-ol-3-one acetate,a novel steroid from the gorgonianEunicella cavolini

Summary The compound titled1 has been isolated from the gorgonianE. cavolini and synthesized from 11-acetoxy-progesterone (3).This work has been carried out in the frame of the Progetto Finalizzato per l'Oceanografia e i Fondi marini, C.N.R., Roma. Acknowledgments. We are grateful to the Zoological Station (Naples) for the collection of Gorgonians. Thanks are also due to Mr G. Scognamiglio, for technical assistance and to Mr C. Di Pinto, for NMR-experiments.     

Synthesis of a pregnancy-associatedα-macroglobulin by human leucocytes

Résumé Le sang des femmes enceintes peut contenir plusierus protéines sériques uniques en leur genre. Celle qui se présente le plus souvent est une -globuline de grand poids moléculaire. Un test in vitro utilisant l'incorporation de¹⁴C-glutamine ou³H-leucine dans la glycoprotéine a montré que celle-ci peut être synthétisée par des leucocytes.

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We thank Dr.J. E. O'Grady and Dr.A. Shephard for obtaining the blood samples. This work was supported by a grant from the Scottish Home and Health Department.     

Inhibition of proliferation by 1-8U in interferon-α-responsive and non-responsive cell lines

Interferon (IFN)-inducible proteins of the 1-8 gene family mediate homotypic adhesion and transduction of antiproliferative signals. Their induction correlates with inhibition of cell growth while they are often repressed in the course of malignant transformation and tumor development. Ras-mediated transformation of mouse mast cells is associated with downregulation of 1-8U expression and interferon-α (IFN-α) treatment reverts the proliferation rate to normal levels together with induction of 1-8U. Conversely, the antiproliferative responses of IFN-α in sensitive human melanoma cells are accompanied by 1-8U induction. Here we provide direct evidence that recombinant expression of 1-8U in human cell lines is sufficient to block cell proliferation. Based on the abundant expression and subcellular localization to the plasma membrane and exosome-like structures, we propose a model capable of explaining the pleiotropic functions of 1-8 family proteins in tumor cells and during normal development. Received 15 January 2003; received after revision 21 March 2003; accepted 25 March 2003 RID="*" ID="*"Corresponding author.     

β2-integrins mediate a novel form of chemoresistance in cycloheximide-induced U937 apoptosis

In this study with cycloheximide (CHX, an inhibitor of protein synthesis) and the human leukaemic cell line U937, a novel form of chemoresistance, which we termed sudden drug resistance (SDR), was identified using Hoechst33258 staining, Western blott and DNA Ladder. CHX^high (10–100 g/ml)-induced apoptosis can spontaneously subside after 4–6 h or can be inhibited by short-term preincubation with CHXlow (2.5 g/ml). Unlike typical multidrug resistance, SDR is not caused by reduced drug accumulation or altered protein expression, and may be associated with a non-P-glycoprotein mechanism. To uncover this underlying mechanism, we focused on U937 cell aggregation promoted by CHX, because cell adhesion has been suggested to influence cell survival and prevent apoptosis. EDTA, or anti-CD18 monoclonal antibody, but not EGTA, acetylsalicylic acid or RGDS tetrapeptide, abrogated this homotypic aggregation and greatly increased CHX-induced apoptosis in a time-dependent manner, while fibrinogen and soluble intercellular adhesion molecule-1 exerted opposite effects. These results establish that ₂-integrin engagement is a key mediator of SDR, although it may be non-exclusive. This finding supplements the classical basis of chemoresistance and may provide another opportunity for improved leukemia therapy.Received 15 April 2004; received after revision 18 May 2004; accepted 21 June 2004     

A fungus pigment of novel type,and the nature of fungus ‘lignin’

Zusammenfassung In den Früchten des höheren PilzesPolyporus hispidus bildet sichin situ ein ligninähnlicher Stoff durch Oxidation-Polymerisation von Phenolen des Phenylpropantyps, hauptsächlich Hispidin (I), dessen Struktur als Enollacton der 3,4-Dihydroxycinnamoylacetessigsäure erkannt wurde.     

Identification of 3α, 17α, 21-trihydroxy-5α-pregnane (allotetrahydro-17α-hydroxy-cortexone) and 3α,21-dihydroxy-5α-pregnane (allo-tetrahydro-cortexone) in human urine

Résumé Le 3, 17, 21-trihydroxy 5-pregnane (allo-tétrahydro-17-hydroxy-cortexone) et le 3,21-dihydroxy 5-prégane (allo-tétrahydro-cortexone) ont été identifiés dans l'urine humaine. Ces composés avaient les mêmes migrations chromatographiques avant ou après acétylation ou oxydation que les respectifs stéroïdes de synthèse.     

Hymenin,a novel α-adrenoceptor blocking agent from the Okinawan marine spongeHymeniacidon sp.

Summary A novel bromine-containing alkaloid, hymenin, has been isolated from the Okinawan marine spongeHymeniacidon sp. as a potent -adrenoceptor blocking agent and its structure determined to be1 on the basis of the spectral data.     

(Z,E)-α-farnesene,main constitutent of the hypertrophied Dufour's gland of the major workers ofPheidole pallidula (Formicidae)

Summary In the European dimorphic ant,Pheidole pallidula, the Dufour's gland of the major workers is hypertrophied and secretes nearly pure (Z, E)--farnesene. This compound is also present in the Dufour's gland of the minor workers but constitutes only around 10% of the volatiles. Chemical polymorphism inP. pallidula is different from that already reported for species ofPheidole from the New World.Aspirante au Fonds National de la Recherche Scientifique.Maître de recherches du Fonds National de la Recherche Scientifique.     

The best of many worlds,or, is quantum decoherence the manifestation of a disposition?

In this paper I investigate whether the phenomenon of quantum decoherence, the vanishing of interference and detectable entanglement on quantum systems in virtue of interactions with the environment, can be understood as the manifestation of a disposition. I will highlight the advantages of this approach as a realist interpretation of the quantum formalism, and demonstrate how such an approach can benefit from advances in the metaphysics of dispositions. I will also confront some commonalities with and differences to the many worlds interpretation, and address the difficulties induced by quantum non-locality. I conclude that there are ways to deal with these issues and that the proposal hence is an avenue worth pursuing.     

The use of benzylpenicillinacylase fromEscherichia coli in the resolution of some racemicβ-,γ-,δ- andɛ-amino-acids

Summary The enzymatic hydrolysis of N-phenylacetyl derivatives of racemic amino-acids having the chiral centre removed from the usual -position is examined. The reaction is found to have different degrees of stereoselectivity. In the case of -amino-acids and of -aminovaleric acid, both enantiomers can be obtained in good yields and high optical purity. S-directed stereochemical preference was found for all the substrates examined.     

Control of HIV infection by IFN-α: implications for latency and a cure

Viral infections, including HIV, trigger the production of type I interferons (IFNs), which in turn, activate a signalling cascade that ultimately culminates with the expression of anti-viral proteins. Mounting evidence suggests that type I IFNs, in particular IFN-α, play a pivotal role in limiting acute HIV infection. Highly active anti-retroviral treatment reduces viral load and increases life expectancy in HIV positive patients; however, it fails to fully eliminate latent HIV reservoirs. To revisit HIV as a curable disease, this article reviews a body of literature that highlights type I IFNs as mediators in the control of HIV infection, with particular focus on the anti-HIV restriction factors induced and/or activated by IFN-α. In addition, we discuss the relevance of type I IFN treatment in the context of HIV latency reversal, novel therapeutic intervention strategies and the potential for full HIV clearance.     

Control of obesity inA vy /a mice by 5α-androstan-17-one

Summary Treating VY/WfL-A ^vy /a mice with 5-androstan-17-one, a mammalian glucose-6-phosphate dehydrogenase inhibitor, prevented the mice from becoming obese. The weight difference between treated and controlA ^vy /a mice was mainly due to a decreased accumulation of triacylglycerol. The compound did not suppress appetite, had no detectable toxicity and did not affect the lipogenesis rates in the liver and carcass. The weight-controlling effect of 5-androstan-17-one inA ^vy /a mice was reversible upon withdrawal of treatment.The authors wish to thank Mr W.R. Gibson and Drs C.G. Culbertson and P.N. Harris for performing the pathological examinations.     

On the production of 12α-hydroxysteroid dehydrogenase fromClostridium group P,strain C48-50 ATCC 29733

Summary The production of 12-hydroxysteroid dehydrogenase ofClostridium group P strain C48-50 was optimized when the organism was grown in the presence of 2% fructose and 0.1% dithiothreitol. It appears that an initial redox potential of less than –160 mV (achieved by autoclaving in the presence of dithiothreitol, dithioerythritol or cysteine) is important in the production of this enzyme.     

In vitro inactivation of gonadotropin receptors, a membrane-associated action?

Under in vitro conditions the time-dependent inactivation process of LH/HCG receptors is nearly identical in ovarian and testicular homogenates but different in gonadal membrane preparations. In the ovarian membranes the loss of binding sites during the first preincubation time is faster than in testicular membranes, especially in membranes of luteinized rat ovaries. Compared with the homogenates, however, the receptor-inactivation in the membranes is generally delayed. The inhibitory effect of metabolic agents on receptor inactivation indicates that membrane-associated actions are involved in this process.