Distribution of C19-steroid conjugates in plasma protein fractions

Zusammenfassung Nach. i.v. Gabe von 7-³H-Dehydroepiandrosteron wurde menschliches Plasma einer präparativen Zonenelektrophorese unterworfen und in Albumine, ₁-, ₂-,- und-Globuline zerlegt. Aus den einzelnen Proteinfraktionen trennte man freie Steroide, Steroid-Sulfokonjugate und -Glukuronoside ab und untersuchte letztere Fraktionen auf ihren Gehalt an markierten C₁₉-Steroiden. Es zeigte sich, dass die Steroid-Sulfokonjugate vornehmlich in der Proteinfraktion der Albumine, die Steroid-Glukuronoside dagegen bevorzugt in der Proteinfraktion der ₁-Globuline auftraten.     

Hypertension expérimentale et protéines sériques

Summary The authors investigated the distribution of serum proteins, especially the ₂ fraction, in rats with artificially induced hypertension (A), in similar rats made normotone by choline-free diet (B), and in a control group (C). A rise in the ₂ fraction of groupA andB was found, without a significant change of the other serum proteins.     

Regulation of rat renal (Na++K+)-adenosine triphosphatase mRNA levels by corticosterone

We investigated the mechanisms for glucocorticoid regulation of rat renal NaK-ATPase activity. Our findings suggest that the magnitudes of corticosterone-induced increases in ₁ mRNA and ₁ mRNA levels are similar in the kidney of the adult adrenalectomized rats. The results also suggest that corticosterone restores NaK-ATPase activity in adrenalectomized rats prior to any enhanced sodium delivery.     

The chemistry of the polymyxin antibiotics

Zusammenfassung Die Chemie der Polymyxine, einer Klasse von basischen Polypeptid-Antibiotika, begann 1954, als durch Gegenstromverteilung erstmals ein definierter Vertreter, das Polymyxin B₁ in reiner Form isoliert werden konnte (L. C.Craig). Partialhydrolyse mit Mineralsäuren führte zum Schluss, dass es sich um Cyclohepta- oder Cyclooctapeptide mit Seitenketten handelt, die, -Diaminobuttersäure (Dab) enthalten (W.Hausmann).Amidartige Verknüpfung der Seitenkette mit einer Fettsäure [(+)-6-Methyloctansäure (MOA) oder 6-Methylheptansäure (IOA)] (S.Wilkinson) verleiht diesen Antibiotika den Charakter von Invertseifen. Sie sind besonders gegen gramnegative Erreger wirksam. Schwierigkeiten bereiteten die Aufklärung der Verknüpfungsweise der Seitenkette (- oder-) und die Beantwortung der Frage, ob das Molekül nebend-Phenylalanin in der Ringsequenz noch einend-, -Diaminobuttersäurerest in Nachbarschaft zur Fettsäure in der Seitenkette enthält. Synthetische Versuche mitd-, -Diaminobuttersäure an dieser Stelle führten zu hochaktiven Produkten, die aber mit natürlichem Polymyxin B₁ nicht identisch waren. Entscheidende Fortschritte wurden mit dem bakteriellen Enzym Nagarse (T.Suzuki) erzielt, das schrittweise die Seitenkette bis zum Ringpeptid abbaut. Dabei ergab sich, dass den Polymyxinen die allgemeine Struktur eines Cycloheptapeptides mit-verknüpfter Seitenkette zukommt (Figur 4).Die Polymyxine B₁ E₁ (Colistin A) sowie Circulin A unterscheiden sich voneinander nur durch eine Variation in der gleichen Dipeptidsequenz des 7-gliedrigen Ringes. Die im Polymyxin B₁ vorhandene Dipeptidsequenzd-Phe-l-Leu ist in Polymyxin E₁ (Colistin A) durchd-Leu-l-Leu und in Circulin A durchd-Leu-Ll-Ile ersetzt. Im Polymyxin D₁ ist neben dem Ersatz der entsprechenden Sequenz durchl-Leu-l-Thr noch ein, -Diaminobuttersäurerest der Seitenkette durch eind-Serin ausgetauscht. Die entsprechenden Verbindungen mit dem Index 2 unterscheiden sich von denjenigen mit dem Index 1 durch einen Austausch der (+)-6-Methyloctansäure durch 6-Methylheptansäure.Die Struktur von Polymyxin B₁ E₁ und Circulin A konnte durch Totalsynthese gesichert werden (K.Vogler). Weitere Fortschritte in der Erforschung der Natur der noch unbekannten Vertreter sind in Kürze zu erwarten.     

Oxidation ofβ-hydroxybutyrate infused into the cortical subarachnoid space

Résumé LeOHB, la concentration du¹⁴CO₂ ainsi que l'activité specifique du¹⁴CO₂ ont été determinées dans l'artère fémorale, le sinus sagittal supérieur et le liquid subarachnoïdal cortical. L'infusion duOHB enregistré a amené la présence de¹⁴CO₂ dans le liquide subarachnoïdal cortical. Les résultats indiquent que leOHB du liquide cérébro spinal peut être oxydé par les tissus à proximité de l'espace subarachnoïdal cortical.     

The mitochondrial processing peptidase: Function and specificity

Targeting signals of mitochondrial precursors are cleaved in the matrix during or after import by the mitochondrial processing peptidase (MPP). This enzyme consists of two nonidentical- and-subunits each of molecular weight of about 50 kDa. In mammals and fungi, MPP is soluble in the matrix, whereas in plants the enzyme is part of the cytochromebc ₁ complex. MPP is a metalloendopeptidase which has been classified as a member of the pitrilysin family on the basis of the HXXEHX₇₆E zinc-binding motif present in-MPP. Both subunits of MPP are required for processing activity. The-subunit of MPP, which probably recognizes a three-dimensional motif adopted by the presequence, presents the presequence to-MPP, which carries the catalytic active site. MPP acts as an endoprotease on chemically synthesized peptides corresponding to mitochondrial presequences. Matrix-targeting signals and MPP cleavage signals seem to be distinct, although the two signals may overlap within a given presequence. The structural element helix-turn-helix, that cleavable presequences adopt in a membrane mimetic environment, may be required for processing but is not sufficient for proteolysis. Binding of the presequence by-MPP tolerates a high degree of mutations of the presequence.-MPP may present a degenerated cleavage site motif to-MPP in an accessible conformation for processing. The conformation of mitochondrial presequences bound to MPP remains largely unknown.     

Secretion of the Dufour gland of the antNothomyrmecia macrops (Hymenoptera:Formicidae)

Summary The Dufour gland of the primitive Australian antNothomyrmecia macrops contains microgram quantities in total of linear alkanes and alkenes from C₁₃ to C₃₀ with heptadecene the major component (66%). In all, 50 substances, including methyl-branched hydrocarbons, aldehydes and acetates, -farnesene and -springene in low nanogram amounts, were identified by gas chromatography-mass spectrometry.     

Discovery of novel avermectins with unprecedented insecticidal activity

Summary A new class of insecticidal and antiparasitic agents, 4-amino-4-deoxy avermectins, has been developed by chemical modification of avermectin B₁. The most effective of these compounds are 1500-fold more potent than avermectin B₁ (abamectin) against the beet armywormSpodoptera exigua and show similar potency against other lepidopteran larvae.     

Average dominance of interocellar bristle polygenes inDrosophila melanogaster

Summary The average dominance of interocellar bristle polygenes inDrosophila melanogaster was computed from the ratio of deviations from the base population mean of the F₁ and the selection lines. The alleles determining interocellar bristle number show recessiveness, more pronounced in low lines than in high lines.     

Avilamycin

Summary A strain ofStreptomyces viridochromogenes produced a new crystalline antibiotic, Avilamycin, related to but not identical with Curamycin and Exfoliatin. Avilamycin, C₆₃H₉₄O₃₅Cl₂, gave on solvolytic degradation the following products: dichloroisoeverninic acid, 2-deoxy-d-rhamnose, 2,6-di-O-methylmannose, 4-O-methylfucose,l-lyxose and 3,5-diacetoxy--caprolactone.     

Okadaxanthin,a novel C50-carotenoid from a bacterium,Pseudomonas sp. KK10206C associated with marine sponge,Halichondria okadai

To study the origins of biologically active substances in marine sponges, a carotenoid produced by a marine bacterium,Pseudomonas sp. strain number KK10206C, which was associated with a marine sponge,Halichondra okadai, was investigated. A visible absorption spectrum-guided isolation procedure led to the isolation of a novel C₅₀-carotenoid, okadaxanthin. Its structure, 2,2-bis(4-hydroxy-2-methyl-2-butenyl)-,-carotene, was elucidated mainly by spectroscopic methods. Okadaxanthin turned out to be a potent singlet oxygen quencher, approximately 10 times as strong as -tocopherol.     

Über die Struktur pflanzlicher Karotinkriställchen

Summary Crystals of carotene in plant cells (carrot root, corona ofNarcissus etc.) have been attributed to the orthorhombic or the hexagonal system. However, an optical investigation showed that they have a lower symmetry. In the case of the crystals in the corona ofNarcissus, the structural identity with synthetic-carotene is proved by X-ray and electron diffraction analysis. Although the geometry of the electron diffraction patterns is almost indistinguishable from hexagonal, its reflections can be identified with those from the planes of the monoclinic lattice of-carotene. The face of the plate-shaped crystals corresponds to (102).     

The lipids of hydrogen-oxidizing bacteria: Occurrence ofcis-9,10-methylene hexadecanoic acid inHydrogenomonas H 16

Zusammenfassung Knallgasbakterien (Hydrogenomonas H 16) wurden unter Speicherbedingungen in Submerskultur herangezogen. Die dabei gespeicherte Poly--hydroxybuttersäure wurde zusammen mit anderen «lokker gebundenen » Lipiden mit Chloroform extrahiert. Die daraus abgetrennten polaren Lipide bestanden ausschliesslich aus Phosphatidyläthanolamin. Die Analyse der Fettsäurezusammensetzung dieses Phosphatids ergab einen Gehalt von 42% (bezogen auf das Gewicht der Gesamtfettsäuren) einer C₁₇-Cyclopropansäure. Durch spektroskopische Untersuchungen und oxydativen Abbau wurde letztere alscis-9,10-Methylenhexadecansäure identifiziert.

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The author is grateful to Prof.H. G. Schlegel for the bacterial culture and to Prof.G. Spiteller for measuring the mass spectra. The technical aid of MissG. Thiele is gratefully acknowledged. The analytical GLC apparatus used has been borrowed from the Deutsche Forschungsgemeinschaft.     

Structure of three isomeric host-specific toxins fromHelminthosporium sacchari

Summary Extended spectroscopic analysis has led to the derivation of complete structures for the 3 isomeric host-specific toxins C₃₉H₆₄O₂₂ previously isolated fromH. sacchari; these compounds represent bis-5-O-(-galactofuranosyl)--galactofuranosides differing in the position of 1 double bond in their sesquiterpenoid aglycone component.Accounts of this work have been presented at the 183rd American Chemical Society National Meeting in Las Vegas, Nevada, March 1982 (abstract 252) and at the Herbstversammlung der Schweizerischen Chemischen Gesellschaft in Bern, October 1982.To whom correspondence concerning this paper should be addressed.     

Die Konstitution der Salamander-Alkaloide

Summary Four alkaloids have been isolated from the skin gland of the Feuer- and Alpensalamander (Salamandra maculosa andatra Laur.). The structure, stereochemistry and absolute configuration of the principal alkaloid, samandarin, have been elucidated by chemical, optical, and X-ray-crystallographic methods. The basic structure of samandarin is derived from 5-androstan by the insertion between C-2 and C-3 of ring A of an NH group which, along with an oxygen bridge between C-1 and C-3, constitutes an oxazolidine ring; at C₁₆ there is a-hydroxyl group. By virtue of its origin and constitution samandarin occupies a unique position among alkaloids.

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Nach der am 15. Juni 1960 in der Aula der Universität Zürich gehaltenen zweitenPaul-Karrer-Vorlesung. Der Vortrag ist zum Teil gekürzt, Ergebnisse der letzten Zeit sind in die vorliegende Fassung eingearbeitet worden.     

Adipokinetic hormones: cell and molecular biology

Adipokinetic hormones AKH I (pGlu-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH₂) and AKH II (pGlu-Leu-Asn-Phe-Ser-Trp-Gly-Thr-NH₂) are synthesized by neurosecretory cells (NSC) of the corpora cardiaca (CC) in the locust,Schistocerca gregaria. These NSC constitute a homogeneous peptide factory as each cell synthesizes both AKH I and AKH II. This homogeneity makes the CC an excellent system in which to study aspects of neuropeptide biosynthesis. This report summarizes recent findings on AKH inactivation and metabolism, as well as on AKH prohormone processing and biosynthesis.     

Dietary sterols: Role in larval feeding behaviour of the Southwestern Corn Borer,Diatraea grandiosella

Zusammenfassung Eine Beziehung zwischen chemischer Struktur und biologischer Aktivität wurde im Einfluss diätetischer Sterole auf das Fütterungsverhalten frisch geschlüpfter Larven vonDiatraea grandiosella gefunden. Die experimentellen Resultate zeigen, dass die C₂₉-Pflanzensterole, -Sitosterol und Stigmasterol, die Futteraufnahme anregen, Cholesterol, 7-Dehydrocholesterol, Ergosterol und -Sitosterolazetat sich in dieser Hinsicht neutral verhalten und Cholesterol-Ester die Futteraufnahme hemmen.     

Nest cell lining of the solitary beeHylaeus bisinuatus (Hymenoptera: Colletidae)

The nest cell lining ofHylaeus bisinuatus (Hymenoptera: Colletidae) was shown by high-resolution solidstate [¹³C]NMR to be composed of lipid polymer and protein. The lipid polymer was shown by reduction and subsequent GC/MS analysis to be comprised of -hydroxy fatty acids (C₂₀, C₂₂, C₂₄ and C₂₆) and fatty alcohols (C₁₆ to C₃₀). The protein portion of the lining had a silk-like amino acid composition.     

Cocarcinogens of the diterpene ester type fromCroton flavens L. and esophageal cancer in Curaçao

Summary From the roots ofCroton flavens L., 3 highly irritant and tumor promoting Croton factorsF ₁–F ₃ and the corresponding 3 cryptic Croton factorsF₁–F₃ were isolated and characterized as novel esters of 16-hydroxy- and 4-deoxy-16-hydroxyphorbol, respectively. These findings suggest that tumor promoters of the phorbol ester type, ingested through the widespread and frequent use ofCroton flavens according to local habits, may be causally related to the well recognized high rate of esophageal cancer on Curaçao.Dedicated to Prof. Dr H. P. Rusch, Director Wisconsin Clinical Cancer Center, Madison, Wis. USA, on occasion of his 70th birthday. We wish to thank Dr J.F. Morton, Morton Collectanea, University of Miami, Florida, USA, for kindly supplying us with the plant material.     

Evaluation of monoaminergic receptors in the genetically epilepsy prone rat

Summary The intensity of sound-induced convulsions in the genetically epilepsy-prone rat (GEPR) was reduced in a dose related fashion by intracerebroventricular administration of dobutamine, (₁ agonist), terbutaline (₂ agonist) or phenylephrine (₁ agonist). BHT-920 (₂ agonist) did not cause a dose-related decrease in sound-induced convulsion intensity. Binding studies showed that whole brain and receptor densities (B_max) were normal while the K_d was increased for the ligand in GEPR brain.Acknowledgment. We are most grateful to Boehringer Ingelheim for generously supplying BHT 920. We are also indebted to Ciba-Geigy Corporation for the gift of terbutaline hydrochloride and phentolamine hydrochloride. The work was supported in part by NIH grant NS 16829.