Scapharca dimeric hemoglobin: A new mechanism of information transfer between globin chains

The homodimeric hemoglobin component present in the red cells of the bivalve molluscScapharca inaequivalvis, HbI, is endowed with high cooperativity in ligand binding. This behaviour is in contrast with that of vertebrate hemoglobins in which cooperativity is associated with a tetrameric assembly and the presence of two types of chain. Analysis of the aminoacid sequence and immunological data suggested that the assembly of HbI differed from that characteristic of vertebrate hemoglobins and hence that cooperativity had an unusual structural basis. Indeed the X-ray structures of the carbonmonoxy and deoxy derivatives at 2.4 resolution showed that in HbI the heme carrying E and F helices are not exposed to solvent as in the vertebrate hemoglobin tetramer, but form the subunit interface and bring the two heme groups practically in direct contact through a network of hydrogen bonds. Ligand binding brings about marked structural changes that are limited to the heme environment, whereas quaternary changes are only minor. The structural changes in the heme environment result in alterations in the network of interactions between the heme groups which lead to changes in ligand affinity. In HbI therefore cooperativity in ligand binding is achieved through direct heme-heme communication as opposed to the long range information transfer operative in the vertebrate hemoglobin tetramer.     

A new pseudoabnormal hemoglobin in hemolytic anemias

Zusammenfassung Es wird ein pseudoanomales Hämoglobin beschrieben, das bei Zirkulation von freiem Hämoglobin im Plasma entsteht und im Urin ausgeschieden wird. Es handelt sich um eine sekundäre Veränderung des Blutfarbstoffes, die von der Haptoglobin- und Glutathionbindung verschieden ist.

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This investigation was supported by a grant from the Swiss National Foundation for the Development of Scientific Research. The technical assistance of MissL. Bargetzi and MissC. Perner is gratefully acknowledged.     

MammalianX-chromosomes: A new kind of composite-typeX in the voleArvicola scherman exitus miller

Zusammenfassung Autoradiographische Untersuchungen mit H³-Thymidin deckten bei der WühlmausA. scherman exitus (2n = 36) eine ungewöhnliche Geschlechtschromosomensituation auf. DasX-Chromosom misst 6,8% von (nA + X). Sein funktioneller Anteil ist zweigeteilt, daneben verfügt es über einen strukturell heterochromatischen und einen stets euchromatisch bleibenden Anteil. DasY ist für ein Säugetier aussergewöhnlich gross (2/3 desX).

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This investigation was in part supported by the Swiss National Foundation and for M.F.L. by the Roche-Studien-Stiftung.     

A new antisickling agent: in vitro studies of its effect on S/S erythrocytes and on hemoglobin S

2-(benzoylamino) pyridinium benzoate (BAPB) has exhibited an antisickling effect with homozygous S/S erythrocytes in vitro. This study suggests that BAPB prevents sickling by inhibiting the gelation of hemoglobin S.     

Purin-6-yltrimethylammonium chloride: A new purine antimetabolite

Zusammenfassung Purin-6-yltrimethylammoniumchlorid wurde synthetisiert. Es erwies sich als ein hämopoetisch toxischer Antimetabolit, wirksam gegen Ehrlich Ascites-Tumor, DC5- und Ca 755-Mäusekrebs.

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Supported in part by grants CY-2903 aud CY-4519 from the National Cancer Institute of the U.S.P.H.S.     

A new antisickling agent: In vitro studies of its effect on S/S erthrocytes and on hemoglobin S

Summary 2-{benzoylamino} pyridinium benzoate (BAPB) has exhibited an antisickling effect with homozygous S/S erythrocytes in vitro. This study suggests that BAPB prevents sicklin by inhibiting the gelation of hemoglobin S.Acknowledgments. This research has been partly funded by a Sickle Cell Research grant from the State of Tennessee to Meharry Medical College. We gratefully appreciate the technical assistance of Mr Rudolf Harlan and Mrs Marjorie Deveau of the School of Graduate Studies. We offer our thanks to Dr J. W. Davis, J. D., Coordinator, Sickle Cell Project, Meharry Medical College for constant encouragement.     

The effect of ligand on the kinetics of the sulfhydryl groups of human hemoglobin with p-mercuribenzoate

The rate of reaction of PMB with the masked sulfhydryls of human hemoglobin derivatives correlates well with the extent of dissociation for various ligands. It is suggested that the alpha1beta2 dimer of hemoglobin participates in the slow step of the reaction with PMB.     

A new kind of motility mutant (non-gliding) inChlamydomonas

Summary Certain mutants ofChlamydomonas moewusii, induced by irradiation with UV-light, lack the flagellar gliding motility normally found in wild-type cells.Acknowledgments. I am grateful for a grant, PCM80-02353, from the National Science Foundation, USA.     

A new peptide coupling agent — phosphonitrilic chloride

Zusammenfassung Phosphonitrilchlorid, dessen Verbindung razemisierungsfrei erfolgt, kann als Reagens zur Synthese von Peptiden verwendet werden.     

The effect of ligand on the kinetics of the reaction of the sulfhydryl groups of human hemoglobin with p-mercuribenzoate

Summary The rate of reaction of PMB with the masked sulfhydryls of human hemoglobin derivatives correlates well with the extent of dissociation for various ligands. It is suggested that the ₁₂ dimer of hemoglobin participates in the slow step of the reaction with PMB.     

Comparison of human adult and fetal hemoglobin: Aminophenol-induced methemoglobin formation

Summary Human fetal hemoglobin was more susceptible to methemoglobin formation in the presence of aminophenols than was adult hemoglobin. This was due to the intrinsic properties of the proteins rather than the presence of methemoglobin reductases.This work was supported by a grant from the National Institute of General Medical Sciences GM-17184.     

Chemotaxis of human neutrophils against gravity: A new method

Summary A new method is described in which human neutrophils were made to migrate upward and against gravity. Thus, the possible effect of gravity on cell migration and consequent detachment of cell after migration have been eliminated.Supported in part by N.I.H. grants: No.HL19628-03, No. DE04898, No. CA24215 and No.RR05493).     

Old drugs with new skills: fenoprofen as an allosteric enhancer at melanocortin receptor 3

The efficiency of drug research and development has paradoxically declined over the last decades despite major scientific and technological advances, promoting new cost-effective strategies such as drug repositioning by systematic screening for new actions of known drugs. Here, we performed a screening for positive allosteric modulators (PAMs) at melanocortin (MC) receptors. The non-steroidal anti-inflammatory drug fenoprofen, but not the similar compound ibuprofen, presented PAM activity at MC₃, MC₄, and MC₅ receptors. In a model of inflammatory arthritis, fenoprofen afforded potent inhibition while ibuprofen was nearly inactive. Fenoprofen presented anti-arthritic actions on cartilage integrity and synovitis, effects markedly attenuated in Mc3r?/? mice. Fenoprofen displayed pro-resolving properties promoting macrophage phagocytosis and efferocytosis, independently of cyclooxygenase inhibition. In conclusion, combining repositioning with advances in G-protein coupled receptor biology (allosterism) may lead to potential new therapeutics. In addition, MC₃ PAMs emerged as a viable approach to the development of innovative therapeutics for joint diseases.     

The effect of nickel chloride on the permeability of the blood-brain barrier

Zusammenfassung Die Permeabilitätsverhältnisse der Blut-Hirn-Schranke nach spezifischer Hemmung der 5-Nucleosid-Phosphatase wurden mittels Fluoreszenzmikroskopie studiert und eine Permeabilitätserhöhung nach Injektion von Nickelchlorid gefunden: Trypanblau kann dabei ins Gehirn penetrieren, was dafür spricht, dass die 5-Nucleosid-Phosphatase bei der Regulation der Kapillarpermeabilität eine bedeutende Rolle spielt.