Radioprotective effects of the immunostimulating lauroylpeptide LtriP (RP 56142)

The lipopeptide lauroyl-L-Ala--D-Glu-L,L-A₂pm (LtriP) increased the resistance of mice to the lethal effect of -ray irradiation. The radioprotective effect was dependent on the doses of LtriP and of radiation. Maximum survival was observed when the lipopeptide was injected on two successive days before irradiation. This activity seems to be related to immunostimulating functions, since the non-immunostimulating analog lauroyl-L-Ala--D-Glu-D,D-A₂pm-Gly, containing D,D-diaminopimelic acid, was not radioprotective. The protective activity might result from an induction of cytokines, such as IL-1, TNF and M-CSF, since LtriP induced the mRNA expression and the secretion of these immunomodulators.     

G-protein signaling: back to the future

Heterotrimeric G-proteins are intracellular partners of G-protein-coupled receptors (GPCRs). GPCRs act on inactive G·GDP/G heterotrimers to promote GDP release and GTP binding, resulting in liberation of G from G. G·GTP and G target effectors including adenylyl cyclases, phospholipases and ion channels. Signaling is terminated by intrinsic GTPase activity of G and heterotrimer reformation – a cycle accelerated by regulators of G-protein signaling (RGS proteins). Recent studies have identified several unconventional G-protein signaling pathways that diverge from this standard model. Whereas phospholipase C (PLC) is activated by G_q and G, novel PLC isoforms are regulated by both heterotrimeric and Ras-superfamily G-proteins. An Arabidopsis protein has been discovered containing both GPCR and RGS domains within the same protein. Most surprisingly, a receptor-independent G nucleotide cycle that regulates cell division has been delineated in both Caenorhabditis elegans and Drosophila melanogaster. Here, we revisit classical heterotrimeric G-protein signaling and explore these new, non-canonical G-protein signaling pathways.Received 21 October 2004; received after revision 20 November 2004; accepted 30 November 2004     

Total synthesis of two cyclodecapeptides exerting polymyxin-like activity

Zusammenfassung Von den vier Cyclodekapeptiden, die als mögliche Strukturen für Polymyxin B₁ vorgeschlagen wurden, konnten nun auch die Ringstrukturen mit 7 Aminosäuren, nämlich 7 und 7 (vgl. Fig.), synthetisiert werden. Diese erwiesen sich im Gegensatz zu 8 und 8 als hochaktive antimikrobielle Wirkstoffe mit Wirkungsqualitäten der Polymyxine. Ob 7 oder 7 mit natürlichem Polymyxin B₁ identisch ist, wird durch weitere Versuche abgeklärt.     

Induction of nuclear styrene monooxygenase and epoxide hydrolase in rat liver

Summary The apparent K_m and V_max of styrene monooxygenase and styrene epoxide hydrolase were determined in intact nuclear preparations from male rat liver after in vivo treatment with phenobarbital and -naphthoflavone, which are known to induce microsomal cytochrome P-450 and cytochrome P-448 respectively. Treatment with phenobarbital does not alter the apparent K_m, but greatly increases the V_max of both nuclear styrene monooxygenase and styrene epoxide hydrolase. Almost the same pattern is observed for styrene monooxygenase after treatment with -naphthoflavone, whereas the same treatment slightly increases both the V_max and K_m value of styrene epoxide hydrolase.This work was supported by the CNR (National Research Council) Contract No. 78.02864.96 within the special program Control of Cancer Growth.     

Reaction of pyridoxal-5′-phosphate with γ-carboxyglutamic acid

Summary Pyridoxal-5-phosphate (PLP) reacts with -carboxyglutamic acid (Gla) to form a stable complex absorbing at 325 nm. It is suggested that a condensation occurs in which the formyl group of PLP reacts with the -amino group and the carbon atom of Gla to give a pyrrolidine derivative.     

Conversion of γ-hydroxybutyrate to γ-aminobutyrate by mouse brain in vivo

Zusammenfassung -Hydroxybutyrat wird im Maushirn in-Aminobutyrat und in verschiedene -Aminosäuren umgewandelt.

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Supported by the Medical Research Council of Canada.     

Comparative analysis of human milk and human blood plasma by means of diffusion-in-gel methods

Zusammenfassung Mit Hilfe von Immunoelektrophorese und Doppeldiffusiontechnik wurden in Humanmilch an Blutplasmaproteinen serologisch identifiziert: Praealbumin, Albumin, Acid Seromucoid, ₁-Glykoprotein (3·5 S), Coeruloplasmin, Haptoglobin, ₂- oder-Lipoprotein, Transferrin, Fibrinogen, _2A-Globulin, _2M-Globulin und-Globulin.     

Singlet oxygen reactivity of bilirubin and related tetrapyrroles

Summary The rates of chemical reactivity (k_R) and physical quenching (k_Q) of singlet oxygen by bilirubin IX, mesobilirubin IX, bilirubin IX dimethyl ester, aetiobilirubin IV, biliverdin IX, biliverdin IX dimethyl ester, aetiobiliverdin IV and an oxodipyrromethene have been determined. The k_R and k_Q values approach the diffusion threshold for the bilirubin-like substrates, but k_RQ by about a factor of 10³ for the verdins. A reaction mechanism involving superoxide ion is suggested. Bilirubin appears to quench singlet oxygen by an electron-transfer mechanism.The authors wish to thank the National Science Foundation (CHE 74-20877) and the National Institute of Child Health (HD 09026) for generous support of this work.     

Rhythmic control of intercostal muscle spindles

Zusammenfassung Afferente Impulsentladungen wurden an der Katze in Pentobarbitalnarkose von einzelnen Hinterwurzelfasern (Thorakalsegment V–VII) abgeleitet. Muskelspindeln und Sehnenorgane wurden identifiziert.Die Muskelspindeln zeigten meist einen ausgeprägten respiratorischen Aktivitätsrhythmus. Motorische-Fasern, der intrafusalen Muskelspindel-Innervation wurden selektiv mit Lidocain blockiert. Dadurch wurde gezeigt, dass die afferente Entladung der Muskelspindeln wesentlich auf ihrer-Innervation beruht. Atmungsrhythmische als auch statische-Aktivierung wurde gefunden. Bei inspiratorischen Spindeln erschien rhythmisch erhöhte-Aktivität meist gleichzeitig mit inspiratorischen Muskelkontraktionen. Während künstlicher Atmung wie auch nach völliger Halsmarkdurchtrennung, konnte die gleiche rhythmische-Aktivierung demonstriert werden. Die Spindeln werden anscheinend durch einen spinalen Reflexmechanismus gesteuert, der offenbar den motorischen Atmungsantrieb verstärkt.

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Supported by Senior Research Fellowship (SF-364) from U.S. P.H.S.     

The action of hydrogen peroxide on amino acids in presence of iron salts and its bearing on photolysis of amino acids

Zusammenfassung Es wurde der Abbau von Aminosäuren durch Wasserstoffsuperoxyd in Gegenwart von Eisensalzen untersucht. Papierchromatographische Analyse zeigte, dass dabei aus-Aminobuttersäure-Alanin und Glycin, aus-Alanin und Serin Glycin entsteht. Die Bildung von-Alanin und Asparaginsäure aus-Aminobuttersäure und von Asparaginsäure aus Glutaminsäure konnte ebenfalls festgestellt werden. Diese Resultate werden in Zusammenhang gebracht mit dem Mechanismus der Photolyse von Aminosäuren in Gegenwart von TiO₂.     

The influence ofBordetella pertussis on the kinetics of antibody production to sheep red blood cells in NMRI mice

Zusammenfassung Die simultane i.p. Injektion von 4 × 10⁸ Schaferythrozyten und 2 × 10⁹ Zellen vonB. pertussis führt im Vergleich zur alleinigen Injektion des Erythrozytenantigens bei NMRI-Mäusen zu einer gesteigerten und verlängerten Proliferation M- und G/A-Antikörper produzierender Milzzellen.

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This work was supported by research grant No. Fi 115/1 of the Deutsche Forschungsgemeinschaft.     

Efficient cell proliferation and predominant accumulation of ɛ-globin mRNA in human leukemic K562 cells which produce mostly Hb Gower 1

Summary Long-term cultures of K562(S) cells in 50–75 M hemin allow the selection of hemin-resistant K562 cells together with cells which proliferate efficiently while fully induced to express the human embryonic globin genes, as the hemoglobin Gower 1 (₂₂) is the predominant hemoglobin produced. Our experiments demonstrate that these K562 cells accumulate mostly -globin mRNA (-globin mRNA/-globin mRNA=2.9) suggesting that the control of hemoglobin expression is at a pretranslational level.We thank Dr Irene Bozzoni (Centro degli Acidi Nucleici, Università di Roma) for the pXCR7 probe. Address for reprint request: R.G. Centro Studi Biochimici sul Morbo di Cooley, Via Borsari 46, I-44100 Ferrara.     

Enzyme-linked immunosorbent assay for measuring serum IgE

Summary Serum IgE was measured by a sandwich method using polystyrene beads coated with anti-IgE -globulin and peroxidase labelled anti-IgE -globulin. The method was simple, and as sensitive as the radioimmunoassay.We are grateful for the skillful assistance of Mrs K. Kobayashi.     

Muscle LIM protein promotes expression of the acetylcholine receptor <Emphasis Type="Italic">γ</Emphasis>-subunit gene cooperatively with the myogenin-E12 complex

Muscle LIM protein (MLP, also referred to as CRP3) is a muscle-specific LIM-only protein, which consists of two LIM motifs. MLP functions as a positive regulator during myogenesis. Here we report that MLP serves as a cofactor regulating the expression of the nicotinic acetylcholine receptor (AChR) -subunit gene in skeletal muscle cells. We found that MLP promoted the expression of the AChR -subunit gene in C2C12 myotubes, but not in C2C12 myoblasts or NIH3T3 fibroblasts. Furthermore, we showed that MLP interacted with myogenin in vivo and enhanced the binding ability of the myogenin-E12 heterodimer to the E boxes in the AChR -subunit gene promoter. Together, these results suggest that MLP promotes the specific expression of the AChR -subunit gene cooperatively with the myogenin-E12 complex during myogenesis.Received 17 May 2004; received after revision 22 July 2004; accepted 26 July 2004     

Über den Phytoöstrogengehalt einiger Pflanzen

Summary The quantity of phyto-estrogens in red clover, hop, peas, and cabbage was estimated by titration on castrated female rats and infantile mice. The level of phytoestrogens was as follows: in hop 1050–2000/kg, in peas 4–6/kg, in cabbage 24/kg, and in red clover 6–9/kg. The author supposes that the sexual disorders described byRosenberger ¹⁴ in cows fed with cabbage, can be explained by the presence of phyto-estrogens in this plant.     

Protein kinase C regulation of GABAA receptors

Pharmacological studies with drugs that activate or inhibit several protein kinase C (PKC) isozymes have identified the PKC family of serine-threonine kinases as important in the regulation of -aminobutyric acid type A (GABA_A) receptor function. PKC modulates GABA_A receptor surface density, chloride conductance and receptor sensitivity to positive allosteric modulators such as neurosteroids, ethanol, benzodiazepines and barbiturates. Recent studies using PKC isozyme-selective reagents and gene-targeted mice have begun to identify critical roles for three isozymes, PKCII, PKC and PKC, in various aspects of GABA_A receptor regulation. Progress in this field touches upon therapeutic areas that are of great clinical importance such as anxiety and addiction. Increased understanding of how PKC regulates GABA_A receptors and which PKC isozymes are involved holds promise for development of new treatments for diverse neuropsychiatric disorders.Received 2 August 2004; received after revision 17 August 2004; accepted 21 August 2004     

Polymorphisme des lipoprotéines et des glycoprotéines sériques chez la Truite

Summary It is shown that there are important differences among the serum proteins of 3 different species of trout. We stress that these genetic variations concern the lipoproteins as well as the glycoproteins. Furthermore, 3 serum proteins ofEsox lucius have antigenic determinants common with the serum proteins ofS. gairdneri; they are an ₂-lipoprotein, an ₂-glycoprotein and a -globulin.     

Über eine neue Herstellung aromatisch substituierter Reduktone

Summary Equimolecular amounts of an aromatic or hetero-cyclic aldehyde, glyoxal and cyanideion combine in slightly alkaline aqueous solution to give 4-aryl-2-hydroxytetronimides (I). These are cyclic reductones comparable to imino-ascorbic acid. Oxidation yields dehydro compounds (III) (4-aryl-2, 3-dioxo-4-hydroxy-butyric acid lactones); hydrolysis gives 4-aryl-2-hydroxy-tetronic acids (V) which are easily decarboxylated to -aryl-lactic acids (VII). On hydrogenation, the compounds I are converted to -aryl-, -dihydroxy-butyramides.