The synthesis of stereoselectively labelled porphobilinogen and its incorporation into protoporphyrin-IX

Summary 11-(R)-²H porphobilinogen, stereospecifically labelled with deuterium in the aminomethylene group has been incorporated into protoporphyrin-IX by haemolysates of chicken erythrocytes. High field NMR spectroscopy confirms that the overall biochemical process is stereospecific, deuterium being retained at the -, -and -meso positions and lost from the -meso position.27 August 1986     

The molecular mechanisms of congenital hypofibrinogenaemia

Congenital hypofibrinogenaemia is characterized by abnormally low levels of fibrinogen and is usually caused by heterozygous mutations in the fibrinogen chain genes (, and ). However, it does not usually result in a clinically significant condition unless inherited in a homozygous or compound heterozygous state, where it results in a severe bleeding disorder, afibrinogenaemia. Various protein and expression studies have improved our understanding of how mutations causing hypo- and afibrinogenaemia affect secretion of the mature fibrinogen molecule from the hepatocyte. Some mutations can perturb chain assembly as in the 153 Cys Arg case, while others such as the B Leu Arg and the B414 Gly Ser mutations allow intracellular hexamer assembly but inhibit protein secretion. An interesting group of mutations, such as 284 Gly Arg and 375 Arg Trp, not only cause hypofibrinogenaemia but are also associated with liver disease. The nonexpression of these variant chains in plasma fibrinogen is due to retention in the endoplasmic reticulum, which in turn leads to hypofibrinogenaemia.Received 17 December 2003; received after revision 19 January 2004; accepted 21 January 2004     

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.     

Chromatography of mast cell sensitizing antibodies in guinea-pigs

Résumé L'inoculation intraveineuse d'albumine humaine (HA), provoque chez le cobaye l'apparition d'un anticorps (-1) sensibilisant les cellules mast (CM) homologues. L'inoculation dans le coussinet plantaire (HA et adjuvant de Freund complet) fait apparaître deux anticorps: l'un (-2) sensibilisant les CM hétérologues, l'autre (dans le-1 ainsi que dans le-2) sensibilisant les CM homologues.

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We thank Mrs.Nava Raz, Mrs.Tamar Minai and Mr.I. Ofek for technical assistance.     

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.     

A new type of antigen induced by chemical linkage ofMycobacterium tuberculosis and γ-globulin

Zusammenfassung Mit Hilfe derPauly'schen Diazo-Reaktion wird humanes -Globulin an humanpathogene, virulenteMycobacterium tuberculosis-Stämme (M) gekoppelt. Das Zustandekommen der chemischen Bindung wurde mit gefärbten Präparaten, elektronenmikroskopischen und immunelektrophoretischen Untersuchungen der Bakterien bewiesen. Die mit-Globulin gekoppeltenM haben ihre Virulenz eingebüsst. In den Versuchstieren wurden Antikörper sowohl gegen -Globulin als auch gegenM gebildet. Durch ersteres wurde das Allergisierungsvermögen vonM gesteigert.     

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.     

The effect of hexosamine inhibitors on the secretion ofγ-globulin

Zusammenfassung Hemmung von Hexosamin vermag die Sekretion von-Globulin durch antikörperproduzierende Zellen unter in vitro Bedingungen nicht zu verhindern. Dies könnte darauf hinweisen, dass unter den gewählten Bedingungen kohlehydratfreie-Globulinmoleküle sezerniert werden.     

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.     

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.     

Butyrate-induced reactivation of the fetal globin genes: A molecular treatment for theβ-hemoglobinophaties

The inherited -hemoglobinopathies (sickle cell disease and thalassemia) are the result of a mutation in the adult () globin gene. The fetal globin chain, encoded by the globin genes, can substitute for the mutated or defective globin chain, but expression of the globin gene is developmentally inactivated prior to birth. Reinducing expression of the normal fetal globin genes is a preferred method of ameliorating sickle cell disease and the thalassemias. Stimulation of as little as 4–8% fetal globin synthesis in the bone marrow can produce >20% fetal hemoglobin in the peripheral circulation, due to enhanced survival of red blood cells containing both sickle and fetal hemoglobin, compared to those containing sickle hemoglobin alone. Butyric acid and butyrate derivatives are generally safe compounds which induce fetal hemoglobin production by stimulating the promoter of the fetal globin genes. An initial trial with the parent compound, delivered as Arginine Butyrate, has demonstrated rapid stimulation of fetal globin expression to levels that have been shown to ameliorate these conditions. Phase 1 trials of an oral butyrate derivative with a long plasma half-life have just begun. These agents now provide a specific new apporach for ameliorating these classic molecular disorders and merit further investigation in larger patient populations.     

Der Einfluss der γ-Globuline auf die Viskosität

Summary Depending on concentration of fibrinogen, increasing concentrations of -globulines cause an exponential increase of viscosity, which is more pronounced, the higher the basic concentration of fibrinogenis. Fibrinogen that is dependent on -globulines and albumin, -globulines that is dependent on albumin, or albumin that is dependent on fibrinogen and -globulines do not show this behaviour.

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Für die zuverlässige Mitarbeit sei der biochem.-techn. Assistentin, Fräulein Ilse Stelter, gedankt.     

Fusimotor effects on position and velocity sensitivity of muscle spindles

Zusammenfassung Primäre und sekundäre Muskelspindelendigungen der Katze wurden mit sowie ohne statische und dynamische -Aktivierung, bei periodischer Dehnung und Entspannung über einen weiten Geschwindigkeitsbereich untersucht. Es wurde die Lage- und Geschwindigkeitsempfindlichkeit bestimmt; dabei wurden 2 Typen statischer -Effekte bei den primären wie auch sekundären Endigungen beobachtet.

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This work was supported by the Swedish Medical Research Council (Project No. 14X-544-02), and by Karolinska Institutet (Reservationsanslaget för främjande av ograduerade forskares vetenskapliga verksamhet).     

The effect of aggregated γ-globulins on immune cytolysis: the role of complement

Zusammenfassung In einem aus Peritonealmastzellen, Antikörper und hitzelabilen Serumfaktoren bestehendenin vitro-System wird die Immunreaktion in Gegenwart von aggregiertem Human--Globulin gehemmt; aggregiertes bovines -Globulin hat dagegen keine derartige Wirkung.

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Supported by the Schweizerische Nationalfonds zur Förderung der wissenschaftlichen Forschung.     

Dissociation constants of the complexes between RNA-polymerase II and amanitins

Riassunto Sono state calcolate le costanti di dissociazione dei complessi fra la RNA-polimerasi II e la metil--amanitina, la -amanitina e la metil-aldoamanitina. La K _d è risultata essere 3.6×10^–9 M per la metil--amanitina e 3.2×10^–9 M per la -amanitina. La metil-aldoamanitina non si lega all'enzima.     

The effects of γ-aminobutyric acid and picrotoxin on the junctional potential and the contraction of crayfish muscle

Résumé L'acide-amino-butyrique et la-alanine reproduisent l'action du transmetteur inhibiteur du système neuromusculaire de l'écrevisse. Ces deux acids aminés diminuent la contraction musculaire. L'acide-amino-butyrique réduit la différence de potentiel et augmente sa décomposition. L'action de ces acides aminés est bloquée par la picrotoxine comme l'est celle du transmetteur inhibiteur.

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The study was supported by Grants B-1089 and B-31 from the National Institute of Neurological Diseases and Blindness, United States Public Health Service. Some of this work was done at the Department of Zoology, Cornell University. We are grateful to Prof.S. C. Wang, Columbia University, for generous assistance.     

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.     

Cephalothin positive direct coombs test. Relationship to serum immunoglobulin concentration

Riassunto L'incubazione in vitro dell'antibiotico cefalotina con sangue intero determina la positività del test di Coombs diretto; la concentrazione di farmaco necessaria a determinare l'anormalità sierologica è correlata negativamente con il tasso di-globuline e diG-globuline. Viene sottolineato l'interesse di tale reperto ai fini clinici, perchè potrebbe indicare la ragione per cui soltanto una parte dei soggetti ai quali viene somministrata la cefalotina sviluppa il test di Coombs diretto positivo.