A tissue-selective prostaglandin E2 analog with potent antifertility effects

Summary N-methanesulfonyl 16-phenoxy--tetranor PGE₂ is a prostaglandin analog which is markedly more tissue selective than PGE₂. This compound is 10–30 times more potent than PGE₂ in animal models which are considered relevant to antifertility effects in humans. In pharmacological tests which are believed to be predictive for side effects in humans, the compound has potency either equal to or less than that of PGE₂.     

Molecular analysis of spontaneous somatic mutants.

Eukaryotic structural gene mutations occurring spontaneously in a mouse myeloma cell line offer the opportunity to study somatic mutation in animal cells at the molecular level. Studies on the myeloma protein and on mRNA have enabled us to characterise four such mutants representing four different mutation mechanisms. The results may have some bearing on the origin of antibody diversity.     

Determinant selection is a macrophage dependent immune response gene function

Immune response (Ir) genes are linked to the species histocompatibility complex and define as yet uncharacterised phenotypic products which control the immune response to thymus dependent antigens. Antibody formation and antigen induced T lymphocyte proliferation are two examples of immune phenomena which, in vivo and in vitro, operate under Ir gene influence. To clarify their mechanism of action and cellular location, we have examined the contribution of antigen structure (amino acid sequence and conformation to Ir gene control of antigen recognition by T lymphocytes) as well as to the critical role played by the antigen presenting macrophage in expression of that control. We report that immune response gene control of antigen recognition operates at least in part at the level of the macrophage.     

A new one-step synthesis of hexahydrocannabinoid analogs

Summary A one-step synthesis of hexahydrocannabinoid analogs (HHC) is described making use of the condensation of phenolic ketones and aldehydes with citronellal in the presence of pyridine.Grateful thanks are accorded to Drs L. Chopard and S. Selvavinayakam for spectral measurements and Dr I. Fleming for useful discussion.R. Mechoulam and Y. Gaoni, Recent advances in the chemistry of Hashish, in: Progress in the Chemistry of Organic natural products, vol. 25, p. 175. Ed. L. Zechmeister. Springer Verlag, Wien 1967; R. Mechoulam, Marijuana Chemistry and Pharmacology, metabolism and clinical effects. Academic Press, New York 1973; R. Mechoulam, N. K. McCallum and S. Burstein, Chem. Rev.76, 75 (1976).     

Survival and endogenous spleen colonies of irradiated mice after skin wounding and hydroxyurea treatment

Summary Wound trauma-induced survival from radiation may be related to increased mitosis in hematopoietic cells. This is supported by the cell cycle-dependent drug hydroxyurea, which 1. blocked survival of wounded mice injected 2 or 3 days after 900 rad and 2. reduced the number of endogenous CFU-s in wounded mice injected shortly before 700 rad.Supported by the Armed Forces Radiobiology Research Institute, Defense Nuclear Agency, under Research Work Unit MJ00018. Views presented in this paper are those of the authors; no endorsement by the Defense Nuclear Agency has been given or should be inferred.Research was conducted according to the principles enunciated in the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Research, National Research Council.     

Insulin stimulation of glucose and amino acid transport in mouse fibroblasts with elevated membrane microviscosity

Summary Basal and insulin-stimulated transport of 2-deoxy glucose and of -aminoisobutyric acid in mouse 3T3 fibroblasts were modulated by increasing the lipid microviscosity of the cell plasma membrane. The kinetics indicate that the insulin effect is induced either by recruitment of new transport carriers or by reduction of the translocation activation energy.This investigation was supported by grant No.5-R01-CA-27471-02, awarded by the National Cancer Institute, Department of Health, Education and Welfare.     

Effect of free fatty acids and cholesterol in vitro on liver plasma membrane-bound enzymes

Summary The effect of cholesterol and fatty acid treatment in vitro was tested on rat liver plasma membrane-bound enzymes and lipid fluidity. The observed alterations of membrane fluidity affect both (Na⁺–K⁺)-ATPase and Mg²⁺-ATPase activities but not 5-nucleotidase; basal adenylate cyclase as well as its hormonal sensitivity were differentially affected by changes of membrane microenvironment.This investigation was partially supported by the Italian National Research Council.     

Blocking by picrotoxin of nigra-evoked inhibition of neurons of ventromedial nucleus of the thalamus

Summary The transmitter substance released by nigro-thalamic fibres is proposed to be -aminobutyric acid, since picrotoxin blocked nigra-evoked monosynaptic inhibition of thalamic neurons.Supported by grants Nos 212009 and 311410 from Ministry of Education of Japan.The authors wish to thank Dr Marjorie Anderson, University of Washington, Seattle, for improving the English.     

Comparative study, in the Allium test, of the cytotoxicity of tubulosine and of 6 synthetized pseudo-tubulosines]

Comparing cytotoxicity of tubulosine and of six newly synthesized pseudo-tubulosines in the Allium test, we have characterized all the current features of protein inhibition. Nevertheless cytotoxicity of the six pseudotubulosines is much weaker. Furthermore, "floating poles anaphasis", a disturbance characteristic of the action of tubulosine, has been found with a lesser intensity with the other compounds.