Cytotoxic and antitumor activity of a new series of heterocyclic compounds: dipyrido (4,3-b) (3,4-f) indoles]

Among newly synthesized compounds derived from the dipyrido [4,3-b] [3,4-f] indole nucleus, two have proved to be particularly active in vitro and in vivo. Their cytotoxic effects on cultured cells have been determined. At non toxic doses, they displayed a pronounced inhibitory effect on experimental L1210 Leukemia. These compounds have a strong affinity for DNA molecules.     

Isolation and description of a new species of Eimeria in rabbits (Orychtolagus cuniculus) : Eimeria pellerdyi P. Coudert, 1977 (Sporozoa, Coccidia)]

Several pure isolates of Coccidia have been obtained in coccidia-free Rabbits by methods taking advantage of differences in the duration of their life-cycle and their site of development, as well as by the inoculation of experimentally immunized animals. Among these isolates one has been shown to represent a new species for which we propose the name: Eimeria pellerdyi P. Coudert, 1977. The oocysts of this species are of medium size (21 x 30 mu), without oocystic residual body. The endogenous life-cycle is completed in 10 days. Schizogony takes place in the superficial epithelial cells of the caecum and the colon, and gamogony in the depth of the Lieberkühn's crypts of the same organs. E. perllerdyi seems to be one of the most pathogenic coccidia species in Rabbits.     

Synthetic and biological activity of 25R and 25S diastereoisomers of dihydroxy-25,26 cholecalciferol (25,25(OH)2D3)]

The separation of 5-cholestene-3 beta, 25 (RS), 25-triol 3,26-diacetate into the diastereoisomers 25R and 25S by means of high pressure liquid chromatography (HPLC) is described. Their absolute configuration cannot be yet established. The less polar diastereoisomer is arbitrarily called 25 zeta1 and the more polar one 25 zeta2. Bromination, dehydrobromination and ultraviolet irradiation conducted to 25 zeta1, 26(OH2D3 and 25 zeta2, 26(OH)2D3 respectively. Their biological activity is described.     

Increased contents of phenylethanolamine, m-octopamine and p-octopamine in the hypothalamus and brain stem of spontanously hypertensive rats (S.H.R. Kyoto)]

Phenylethanolamine, p-octopamine and m-octopamine contents were determined in the hypothalamus and the brain stem of spontaneously hypertensive Rats (S.H.R. Kyto) and the corresponding controls (Wistar Kyoto). In three-week-old Rats, phenylethanolamine and p-octopamine are found to be present in S.H.R. hypothalamus and brain stem at concentrations twice as high as compared to Wistar Kyoto Rats. The amount of m-octopamine is 5-fold higher in the brain stem of S.H.R. Rats as compared to Wistar Kyoto Rats.     

Human spleen: a new and potent source of human interferon for experimental and therapeutic use

Cells of a single human spleen, cultivated in vitro and induced by Sendai virus, produce constantly more than 10(8) units of interferon per spleen. This interferon can be used for therapeutic assays and new basic investigations.     

Light and electron microscopic localization of cholinesterase activity in a marine invertebrate (Nereis pelagica L., Annelida, Polychaeta)]

High specific and nonspecific cholinesterase activities have been demonstrated in the whole nervous system of Nereis. These might reveal the existence of a cholinergic nervous system whose control would be exerted in different sites (central nervous centers, muscular junctions...).     

Cytoimmunological study of the corticotrophic and corticomelanotrophic cells in the adenohypophysis of Boops salpa L. (marine teleost) in different experimental conditions (variation of salinity and of background color)]

The cytoimmunological study of the adenohypophysis of Boops salpa (marine Teleost), in different experimental conditions confirmed that the MacConaill's hematoxyline-positive cells contain: 1. ACTH (Corticotrophic Hormone) in the pars distalis, 2. MSH (Melanocyte-Stimulating Hormone) and ACTH in the pars intermedia.     

Discovery and purification of a virus in gland hyperplasia of insects. Study of Merodon equistris F. (Diptera, Syrphidae)]

ADNA virus was purified from the salivary gland affected by a large proliferation in the Diptera Merodon equestris. Structure, nucleic acid as well as development and intracellular cycle of the virus have been characterized.     

Cumulative record of motor activity. (A new procedure and its use for the study of central stimulant drugs)

Zusammenfassung Eine Methode zur kumulativen Registrierung spontaner motorischer Aktivität kleiner Tiere wird beschrieben. Die Wirksamkeitsbestimmung aus dem kumulativen Rekord und die analytische Bedeutung der Methode für die Wirkungsweise zentralstimulierender Substanzen wird diskutiert.     

Studies onHolothuria polii (Echinodermata) antibacterial proteins. I. Evidence for and activity of a coelomocyte lysozyme

Summary Lysozyme activity has been detected in coelomocyte lysate of the echinodermHolothuria polii. The bacteriolytic reaction was stable when the lysate was heated in acidic buffer but heat-labile in alkaline medium. An incubation temperature of 35°C, acidic pH values (5.2 and 6.2) and an ionic strength of 0.175 were found to be the best conditions for the coelomocyte enzymatic activity. A low level of lysozyme was also evidenced in cell-free coelomic fluid where it could represent a basal defense level of bacteriolytic molecules released by the coelomocytes.Acknowledgments. This work was supported in part by a grant from MRES (C. C.). The authors thank M. Lasségues and F. Lassalles for their help and criticism.     

Structure and stereochemistry of attenuol,a new lignan fromKnema attenuata (Wall.) Warb.

Summary A new lignan attenuol has been isolated from the bark ofKnema attenuata (Wall.) Warb. Its structure (I) is deduced on the basis of analytical and spectral data. The compound has been assigned the absolute configuration as 2S,3R-dimethyl-1S-(p-hydroxyphenyl)-6,7-methylenedioxytetralin (III).Contribution No. 487 from the Ciba-Geigy Research Centre.Acknowledgments. We thank Dr H. Fuhrer and Dr P. Moser of Ciba-Geigy Ltd. Basle for the NMR spectral data and ORD determinations and Dr S. Selvavinayakam and his colleagues for the analytical results.     

The effect of methallibure (I.C.I. 33, 828) on the steroidogenesis in the ovary and testis of a fresh water teleost,Cyprinus carpio

Summary Methalibure treatment of matureCyprinus carpio causes a marked reduction in the steroidogenesis, as indicated by the fall in 3-HSD activity in the gonads. Significance of these results is discussed.K.K. is thankful to University Grants Commission for a fellowship. Thanks are also due to I.C.I. England for the supplies of methallibure.     

Effects of [N-(2-oxo-3,5,7-cycloheptatrien-1-yl)] aminooxoacetic acid ethyl ester (AY-25,674) on cyclic 3',5'-nucleotide formation and phosphodiesterase activity.

The orally-effective antiallergic compound [N-(2-oxo-3,5,7-cycloheptatrien-1-yl)] aminooxoacetic acid ethyl ester (AY-25,674) exhibited a potency equivalent to or 3 times less than theophylline in inhibiting guinea-pig lung and beef heart PDE, respectively, AY-25,674 did not affect the basal activity of guinea-pig lung adenyl cyclase. Although part of the antiallergic activity of AY-25,674 may be due to the ability to elevate cyclic AMP levels by PDE inhibition, other modes of action appear to be of greater relevance.     

Something old,something new and something borrowed: emerging paradigm of insulin-like growth factor type 1 receptor (IGF-1R) signaling regulation

The insulin-like growth factor type 1 receptor (IGF-1R) plays a key role in the development and progression of cancer; however, therapeutics targeting it have had disappointing results in the clinic. As a receptor tyrosine kinase (RTK), IGF-1R is traditionally described as an ON/OFF system, with ligand stabilizing the ON state and exclusive kinase-dependent signaling activation. Newly added to the traditional model, ubiquitin-mediated receptor downregulation and degradation was originally described as a response to ligand/receptor interaction and thus inseparable from kinase signaling activation. Yet, the classical model has proven over-simplified and insufficient to explain experimental evidence accumulated over the last decade, including kinase-independent signaling, unbalanced signaling, or dissociation between signaling and receptor downregulation. Based on the recent findings that IGF-1R “borrows” components of G-protein coupled receptor (GPCR) signaling, including β-arrestins and G-protein-related kinases, we discuss the emerging paradigm for the IGF-1R as a functional RTK/GPCR hybrid, which integrates the kinase signaling with the IGF-1R canonical GPCR characteristics. The contradictions to the classical IGF-1R signaling concept as well as the design of anti-IGF-1R therapeutics treatment are considered in the light of this paradigm shift and we advocate recognition of IGF-1R as a valid target for cancer treatment.     

Semi-synthesis and proposed structure of platelet-activating factor (P.A.F.): PAF-acether an alkyl ether analog of lysophosphatidylcholine]

We have studied the molecular structure of platelet-activating factor" (P.A.F.), a mediator of inflammation obtained from blood leukocytes, macrophages, and platelets themselves. We have semi-synthetized a substance that possesses all the known physicochemical and biological characteristics of P.A.F. from hog leukocytes. This was performed by successive methylation, hydrogenation, and acetylation of lysophosphatidylethanolamine plasmalogen. We therefore propose the following structure for P.A.F.: 1-0-alkyl-2-acetyl-glyceryl-3-phosphorylcholine. This molecular structure is not yet described among the numerous substances capable of inducing platelet aggregation and release.