Circling behavior induced by phencyclidine in mice and its inhibition by naloxone

Phencyclidine (PCP), when given to mice, induces general hyperactivity and rapid circling, similar to that caused by morphine. These effects are partially antagonized by naloxone.     

Amantadine modulates phencyclidine binding site sensitivity in rat brain

Summary Amantadine, an antiviral drug with various CNS effects, significantly increases the affinity of the [³H] PCP receptor in rat brain. Rimantadine, an analogue of amantadine devoided of CNS effects, does not have any affect on the [³H] PCP receptor. These results may suggest that some of the CNS actions of amantadine are related to an interaction with the PCP receptor.Acknowledgments. We thank Dr W. K. Schmidt (E.I. Dupont, Newark, Delaware) for gifts of amantadine and rimantadine. Dr R. Quirion is a fellow of the Medical Research Council of Canada.     

Comparison of counterimmunoelectrophoresis (CIE), latex agglutination (LA) and staphylococcal coagglutination (COAG) in pneumococcal antigen detection in vitro

Summary CIE was compared to agglutination assays employing commercial kits (Directigen, Phadebact), as well as our own LA and COAG reagents, in detection of pneumococcal capsular polysaccharide (PCP) antigens in vitro. Directigen provided the most sensitive assay. CIE was of comparable sensitivity except for PCP antigen types 7 and 14.     

Comparison of counterimmunoelectrophoresis (CIE), latex agglutination (LA) and staphylococcal coagglutination (COAG) in pneumococcal antigen detection in vitro

CIE was compared to agglutination assays employing commercial kits (Directigen, Phadebact), as well as our own LA and COAG reagents, in detection of pneumococcal capsular polysaccharide (PCP) antigens in vitro. Directigen provided the most sensitive assay. CIE was of comparable sensitivity except for PCP antigen types 7 and 14.     

Extraadrenal adrenaline formation by two separate enzymes

Summary Adrenaline (A) is synthesized in the adrenal medullae by the enzyme phenylethanolamine-N-methyltransferase (PNMT). After surgical removal of the adrenal medullae tissue A levels ranged from 22% of control in the heart to 125% of control in the liver. Use of a novel assay to measure tissue A formation revealed that many tissues can synthesize A using PNMT and another enzyme that N-methylates both noradrenaline and dopamine. These enzymes are non-neuronal, inducible and synthesize a major fraction of tissue and urine A.     

Oxidative phosphorylation inTrypanosoma cruzi

Zusammenfassung In Epimastigoten vonT. cruzi wird die oxydative Phosphorylierung bewiesen durch: 1. Beseitigung der Atmungskontrolle durch Zugabe von entkoppelnden Substanzen (CCP und PCP); 2. Hemmung der Phosphorylierung durch Antimycin mit gleichzeitiger Reduktion von Cytochrom b; 3. Atmungshemmung durch Dicyclohexylcarbodiimid (DCCD); 4. Verminderung des intrazellulären ATP durch CCP, DCCD und Cyanid.

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Career Investigator, CONICET.     

Extraadrenal adrenaline formation by two separate enzymes

Adrenaline (A) is synthesized in the adrenal medullae by the enzyme phenylethanolamine-N-methyltransferase (PNMT). After surgical removal of the adrenal medullae tissue A levels ranged from 22% of control in the heart to 125% of control in the liver. Use of a novel assay to measure tissue A formation revealed that many tissues can synthesize A using PNMT and another enzyme that N-methylates both noradrenaline and dopamine. These enzymes are non-neuronal, inducible and synthesize a major fraction of tissue and urine A.     

Large protein complexes retained in the ER are dislocated by non-COPII vesicles and degraded by selective autophagy

Multisubunit protein complexes are assembled in the endoplasmic reticulum (ER). Existing pools of single subunits and assembly intermediates ensure the efficient and rapid formation of complete complexes. While being kinetically beneficial, surplus components must be eliminated to prevent potentially harmful accumulation in the ER. Surplus single chains are cleared by the ubiquitin–proteasome system. However, the fate of not secreted assembly intermediates of multisubunit proteins remains elusive. Here we show by high-resolution double-label confocal immunofluorescence and immunogold electron microscopy that naturally occurring surplus fibrinogen Aα–γ assembly intermediates in HepG2 cells are dislocated together with EDEM1 from the ER to the cytoplasm in ER-derived vesicles not corresponding to COPII-coated vesicles originating from the transitional ER. This route corresponds to the novel ER exit path we have previously identified for EDEM1 (Zuber et al. Proc Natl Acad Sci USA 104:4407–4412, 2007). In the cytoplasm, detergent-insoluble aggregates of fibrinogen Aα–γ dimers develop that are targeted by the selective autophagy cargo receptors p62/SQSTM1 and NBR1. These aggregates are degraded by selective autophagy as directly demonstrated by high-resolution microscopy as well as biochemical analysis and inhibition of autophagy by siRNA and kinase inhibitors. Our findings demonstrate that different pathways exist in parallel for ER-to-cytoplasm dislocation and subsequent proteolytic degradation of large luminal protein complexes and of surplus luminal single-chain proteins. This implies that ER-associated protein degradation (ERAD) has a broader function in ER proteostasis and is not limited to the elimination of misfolded glycoproteins.     

Enzymatic N-acetylation of tryptamine by brain homogenates of Locusta migratoria before and after intoxication by chlordimeform or lindane (author's transl)]

Brain homogenates of Locusta migratoria are found to possess enzyme capable of catalyzing the N-acetylation of tryptamine. A main product of the enzymatic reaction is isolated and identified as N-acetyltryptamine by chromatography analyse. Both insecticides, chlordimeform and lindane, inhibit enzyme activity. A direct correlation between the degree of intoxication and acetylation of tryptamine is described.     

Dynamics of estrogen binding by uterine cells in vivo

Summary The dynamics of the in vivo binding and release of tritiated estradiol in different uterine cell types are described. The very early binding of estrogens by the cytosol-nuclear and the eosinophil receptor systems is in accordance with the hypothesis that some estrogenic effects are mediated by these receptor systems.Acknowledgments. This work was supported in part by grant 2015 from the Servicio Técnico de Desarrollo Científico y Creación Artística of the University of Chile to the Laboratory of Experimental Endocrinology, Department of Experimental Morphology, University of Chile Medical School, by a Population Council Fellowship to Dr A. Tchernitchin from 1970 to 1972, by a Rockefeller Foundation grant to the Laboratories of Reproductive Biology, University of North Carolina Medical School, and by USPHS grant HD00371 to the Children's Hospital of Philadelphia. We wish to thank Drs W. E. Stumpf (Laboratories of Reproductive Biology, University of North Carolina Medical School) and A. M. Bongiovanni (Children's Hospital of Philadelphia) for the facilities available.     

Membrane damage by coelomic fluid from Holothuria polii (Echinodermata)

Rabbit erythrocyte membranes lyzed by Holothuria polii coelomic fluid, observed under the electron microscope, present lesions consisting of irregular holes which are heterogeneous in size (ranging from 50 A to 250 A) and ultrastructurally different from the ring-like structure produced by human complement. The protein pattern associated with the lyzed membrane was also examined.     

Hydrolysis of N-phenylacetyl-a-methyl-alpha-amino acids by benzylpenicillinacylase

Enzymatic hydrolysis of several racemic N-phenylacetyl-alpha-methyl-alpha-amino acids containing an additional aliphatic, aromatic or polar substitutent on the chiral carbon atom, has been studied by using benzylpenicillinacylase from Escherichia coli A.T.C.C.9637. Both the rate of hydrolysis and the stereoselectivity were found to be considerably lower than in the case of natural alpha-amino acids. Steric and electronic factors in the side chains influencing the stereoselectivity are discussed. Key words. Benzylpenicillinacylase; enzymatic hydrolysis; alpha-methyl-alpha-amino acids.     

The lectin fromViscum album L. purification by biospecific affinity chromatography

Summary A lectin fromViscum album which specifically binds to D-galactose was isolated by affinity chromatography on O-lactosyl-, O-galactosyl-polycarylamide or hydrolized sepharose 4 B. Some serological and physicochemical properties of the agglutinin are reported.     

Thiarubrine A,a bioactive constituent ofAspilia (Asteraceae) consumed by wild chimpanzees

Summary Two African species ofAspilia (Asteraceae), which are used medicinally by man and which are eaten by wild chimpanzees in an unusual manner, were found to contain the potent antibiotic thiarubrine A as a major leaf phytochemical. Its presence in leaf material strengthens the view that the feeding behavior of wild chimpanzees is related to special physiological or pharmacological effects on the animals.     

Stimulation of induction or inhibition of crown-gall tumor development by RNA-fragments U2. Interference by auxin]

RNA-fragments U2 obtained by mild degradation with RNase U2 of ribosomal RNA containing A and G nucleotides in excess are capable of exhibiting either a stimulatory effect on the induction of Crown-gall tumors or an inhibitory action on their subsequent development. These different effects are dependent on the moment at which RNA-fragments were introduced into wounded Pea seedlings infected by Agrobacterium tumefaciens B6. The results obtained in vitro and in vivo suggest that an interaction between auxin and RNA-fragments U2 may take place, either increasing the tumor induction or inhibiting the proliferation of tumourous cells.     

Inhibition of tryptophan uptake in Aspergillus fumigatus by tryptamine

Summary The tryptophan uptake was inhibited considerably in tryptamine grown cells. This inhibition was due to feed-back inhibition and not to repression.The authors are greatful to Prof. V. V. Modi for his interest in this work. The award of research fellowship by M. S. University of Baroda to A. R. G. is greatfully acknowledged.     

Destruction of virus infected cells by neutrophils and complement

Summary The paper describes an antibody independent mechanism of cytotoxicity whereby virus infected but not uninfected cells are destroyed by the combined presence of neutrophils and complement.Supported by A.I. 14981 and by the MRC of Canada.Acknowledgment. We thank C.J. Wust for invaluable discussions.     

Activation of complement by trypanosomes

Summary Factors exhibiting anti-complementary activity released from trypanosomes after incubation at 20°C were described. The active material was shown to consume the first component of bovine complement. While the anticomplementary factor(s) from T. lewisi could activate bovine, human and guinea pig complement, the factor(s) from T. congolense was observed to activate bovine complement, but not guinea pig and only slightly human complement. The roles of complement activating factor(s) of trypanosomes in the pathology of the disease are discussed.This project is supported by National Research Council of Canada grant A 0068 and a grant from the International Development Research Centre.     

Thiarubrine A, a bioactive constituent of Aspilia (Asteraceae) consumed by wild chimpanzees

Two African species of Aspilia (Asteraceae), which are used medicinally by man and which are eaten by wild chimpanzees in an unusual manner, were found to contain the potent antibiotic thiarubrine A as a major leaf phytochemical. Its presence in leaf material strengthens the view that the feeding behavior of wild chimpanzees is related to special physiological or pharmacological effects on the animals.