A suggested mechanism for the action of choline esters on animal organs,inferred from a study of the effect of choline-,β-methylcholine-, and thiocholine-esters

Résumé Le mécanisme d'action des esters carboxyliques de la choline commence, probablement, par une hydrolyse enzymatique provoquée par une des cholinestérases. Les produits de l'hydrolyse réagissent avec un facteur inconnu, dont la spécificité est cependant définissable par la structure du résidu cholinique.     

Identification of ϱ-antigenic determinants on the surface,of mouse T-lymphocytes

Summary A monospecific antiserum has been prepared in rabbits against purified -antigen, a 100,000 mol.wt glycoprotein found on the surface of mouse L-cells. This antiserum has been employed to demonstrate the presence of -antigenic determinants selectively on the surface of mouse T-, but not B-lymphocytes.We thank Drs A. Christopher and R. Hunt for advice during the course of these studies. This work was supported by grants from the U.S. Public Health Service and the American Cancer Society.     

Comparison of the effects of lithium,β-phenylethylamine and tyrosine onXenopus embryos

Résumé On a étudié les effets du lithium, de la -phényléthylamine et de la tyrosine sur le développement embryonnaire deXenopus laevis. La tyrosine n'a pas d'effet, mais le lithium ou la -phényléthylamine ont végétalisé les embryons s'ils ont été exposés avant le stade blastula.     

Melatonin, hormone of darkness and more – occurrence, control mechanisms, actions and bioactive metabolites

In its role as a pineal hormone, melatonin is a pleiotropic, nocturnally peaking and systemically acting chronobiotic. These effects are largely explained by actions via G protein-coupled membrane receptors found in the suprachiasmatic nucleus, but also in numerous other sites. Nuclear (ROR/RZR), cytoplasmic (quinone reductase-2, calmodulin, calreticulin) and mitochondrial binding sites and radical-scavenging properties contribute to the actions of melatonin. Regulation of pineal melatonin biosynthesis is largely explained by control mechanisms acting on arylalkylamine N-acetyltransferase, at the levels of gene expression and/or enzyme stability influenced by phosphorylation and interaction with 14-3-3 proteins. Melatonin is not only a hormone but is also synthesized in numerous extrapineal sites, in which it sometimes attains much higher quantities than in the pineal and the circulation. It is also present in many taxonomically distant groups of organisms, including bacteria, fungi, and plants. Moreover, melatonin is a source of bioactive metabolites, such as 5-methoxytryptamine, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine and N(1)-acetyl-5-methoxykynuramine.     

β-Methyl carboline,a benzodiazepine inverse agonist,attenuates the effect of triazolam on the circadian rhythm of locomotor activity

Summary The benzodiazepine triazolam, the benzodiazepine inverse agonist, -methyl carboline (-CCM) or both, were administered to adult male hamsters under conditions of constant light. When given alone, triazolam induced phase advances in the circadian activity rhythm of about 90 min, while -CCM when given alone, had no effect on phase of the activity rhythm. However, when triazolam and -CCM were given at the same time, the magnitude of the phase advances induced by triazolam were attenuated to about 30 min. These data, in conjunction with previous results, provide pharmacological evidence for a GABAergic system involved in the regulation of a central circadian pacemaker.     

Effects of physalaemin, a vaso-active peptide from amphibian skin, on the excitability of an identifiable molluscan giant neurone of Achatina fulica Férussac.

We examined effects of several vasoactive peptides (substance P, physalaemin, neurotensin, bradykinin, angiotensin etc.) on the excitability of molluscan giant neurones identified in the subesophageal ganglia of Achatina fulica Férussac. Of these peptides, only physalaemin showed a remarkable excitatory effect on a giant tonically autoactive neurone.     

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.     

PPAR γ partial agonist, KR-62776, inhibits adipocyte differentiation via activation of ERK

Indenone KR-62776 acts as an agonist of PPARγ without inducing obesity in animal models and cells. X-ray crystallography reveals that the indenone occupies the binding pocket in a different manner than rosiglitazone. 2-Dimensional gel-electrophoresis showed that the expression of 42 proteins was altered more than 2.0-fold between KR-62776- or rosiglitazone-treated adipocyte cells and control cells. Rosiglitazone down-regulated the expression of ERK1/2 and suppressed the phosphorylation of ERK1/2 in these cells. However, the expression of ERK1/2 was up-regulated in KR-62776-treated cells. Phosphorylated ERK1/2, activated by indenone, affects the localization of PPARγ, suggesting a mechanism for indenone-inhibition of adipogenesis in 3T3-L1 preadipocyte cells. The preadipocyte cells are treated with ERK1/2 inhibitor PD98059, a large amount of the cells are converted to adipocyte cells. These results support the conclusion that the localization of PPARγ is one of the key factors explaining the biological responses of the ligands. Received 04 March 2009; received after revision 13 March 2009; accepted 17 March 2009     

Dopamine-β-hydroxylase,adrenaline, noradrenaline and dopamine in the venous blood of adrenal gland of man: A comparison with levels in the periphery of the circulation

Summary In 10 human subjects plasma dopamine--hydroxylase activity was found in the adrenal vein blood to be as high as in the periphery of the circulation. Adrenaline concentration in the adrenal vein blood was in the mean 170 times, noradrenaline concentration 11 times and dopamine concentration little higher than levels in the periphery.This study was supported by the Deutsche Forschungsgemeinschaft.     

Good, bad or offal? The evaluation of raw pancreas therapy and the rhetoric of control in the therapeutic trial, 1925

In 1925 a debate erupted in the correspondence columns of the British Medical Journal concerning the effectiveness of eating raw pancreas as a treatment for diabetes. Enthusiasts were predominantly general practitioners (GPs), who claimed success for the therapy on the basis of their clinical impressions. Their detractors were laboratory-oriented 'biochemist-physicians,' who considered that their own experiments demonstrated that raw pancreas therapy was ineffective. The biochemist-physicians consistently dismissed the GPs' observations as inadequately 'controlled'. They did not define the meaning of 'control' in this context, although it clearly did not have the term's present-day meaning of a trial employing an untreated comparison group of patients. Rather, the physician-biochemists' 'properly controlled' experiments involved careful regulation of their patients' diet and other environmental factors, and evaluation of the therapy's success through biochemical, rather than just clinical, criteria. However, my analysis suggests that these factors alone are inadequate to account for the biochemist-physicians' dismissal of the GPs' work as 'uncontrolled'. I suggest that the biochemist-physicians were deliberately exploiting the powerful rhetorical connotations of the term 'control'. Ultimately, they implied that only a trial which they themselves had conducted could be deemed 'adequately controlled'.     

Crystal and molecular structure of 3, 3′-dibromobenzophenone

Résumé La structure du cristal de 3, 3-dibromobenzophénone a été définie par l'emploi de données obtenues par rayons X dans trois dimensions. Les distances et les angles de liaison ont été obtenus et l'on a trouvé que deux anneaux de phényle de la molécule ne sont pas dans le même plan, l'angle compris entre eux étant de 39,9°.     

The in vivo expression of the globin genes of theβ cistron in γ-,δ-, andδβ-thalassemia heterozygotes

There is considerable evidence suggesting that the switch from to and chain production after birth is due, in part, to silencing of the genes by stage-specific factors which bind to their promoters and to the competition from the adult ( and ) genes for a common enhancer element located in the locus control region. As a consequence one can expect that the increased Hb F production in adults with hereditary persistence of fetal hemoglobin or -thalassemia is directed mainly by -globin genes in cis to the deletion(s) responsible for these conditions. Here we review data on heterozygotes with -, -, or -thalassemia, who also had an^AT mutation, in cis or in trans, which was used as a marker of gene expression. The results show that a deletion affecting adult genes favors the expression of genes in cis, while the deletion of a single gene does not affect the expression of the gene in cis but leads to a faster switch postnatally.     

5′-Nucleotidase activity in liver homogenates of rats treated with CCl4, colchicine,cycloheximide, emetine,ethanol, ethionine and 5-fluorotryptophan

Summary 5-Nucleotidase activity, an enzyme marker of the plasma membranes, increases in female rat liver homogenates following ethionine administration, while homogenates from males show no changes. Treatment with CCl₄, colchicine, cycloheximide, emetine, ethanol and 5-fluorotryptophan does not significantly modify the 5-nucleotidase activity of liver homogenates of either female or male rats.     

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.     

The development of the Laplace transform, 1737–1937

This paper, the first of two, follows the development of theLaplace Transform from its earliest beginnings withEuler, usually dated at 1737, to the year 1880, whenSpitzer was its major, if himself relatively minor, protagonist. The coverage aims at completeness, and shows the state which the technique reached in the hands of its greatest exponent to that time,Petzval. A sequel will trace the development of the modern theory from its beginnings withPoincaré to its present form, due toDoetsch.     

The presence of β-phenylethylamine,p-tyramine,m-tyramine and tryptamine in ganglia and foot muscle of the garden snail (Helix aspersa)

Summary The concentrations of -phenylethylamine,p-tyramine,m-tyramine,m-octopamine and tryptamine in the ganglia or foot muscle ofHelix aspersa range from <0.6 to 11 ng/g.p-Octopamine levels are higher in ganglia (327 ng/g) than in foot muscle (4.1 ng/g). Dopamine and 5-hydroxytryptamine range from 840 to 2710 ng/g while their acid metabolites, 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylacetic acid and 5-hydroxyindoleacetic acid range from <20 to 130 ng/g.Acknowledgments. We thank Dr A.A. Boulton for helpful discus sion, Dr D.A. Durden for supervising the mass spectrometric analyses, Dr B.A. Davis for the synthesis of the deuterated standards, G.H. Wheatley, E.P. Zarycki and M. Mizuno for expert technical assistance, and Saskatchewan Health and the MRC of Canada for providing financial support.     

26-Hydroxy-β-ecdysone,a metabolite of β-ecdysone in the blowfly,Calliphora erythrocephala

Summary 26-Hydroxy--ecdysone has been identified as a metabolite of the moulting hormone, -ecdysone inCalliphora erythrocephala.