Isolation of 2-S-cysteinyldopa and 2,5-S,S-dicysteinyldopa from the urine of patients with melanoma

Summary Urine from patients with melanoma metastases is shown to contain, in addition to the previously described 5-S-cysteinyldopa (I), 2 closely related metabolites which have been isolated and identified as 2-S-cysteinyldopa (II) and 2, 5-S, S-dicysteinyldopa (III).Supported by grants from the Swedish Cancer Society (No. 626-B76-05XB and 869-B75-01P), the Swedish Medical Research Council (No. B76-04X-00056-12), and the Walter, Ellen and Lennart Hesselman Foundation for Scientific Research. Professor Prota was a visiting scientist of the Swedish Cancer Society (No. 626-B75-04V). The authors are indebted to Dr Soshuke Ito for samples of 2-S-cysteinyldopa and 2,5-S,S-dicysteinyldopa.     

Eubotriol and eubol,new diterpenes fromSideritis euboea

Summary 2 new diterpenes Eubotriol (ent-kaur-16-ene-7, 15, 18triol) (I), and eubol (ent-kaur-16-ene-7-acetoxy-15, 18 diol) (II) have been isolated from Sideritis euboea Helder.This work was supported by National Research Council (C.N.R.), Roma.     

Morphological characteristics of the secretory granules in pancreaticβ cells from species with identical primary structures of insulin

Zusammenfassung Die Primärstruktur des Insulins ist bei Hund und Schweinidentisch. Elektronenmikroskopisch wurde festgestellt, dass die sekretorischen Granulae der pankreatischen-Zellen bei beiden Arten eine unregelmässige Form haben. Eine quantitative Analyse ergab jedoch, dass die-Granulae des Hundes länger sind als die des Schweines.

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Supported by the United States Public Health Service (Grant No. 5 R05 TW00083-03) and the Swedish Medical Research Council (Grant No. K67-12X-562-03).     

Revised structures for iselin and iliensin and the identity of the former with archangelin

Summary Structures of iselin and iliensin have been revised. The structure (Ib) is secured for iselin by a direct comparison (m.p., UV, IR, PMR) with archangelin. The synthesis of iliensin (IIb) has been effected through the condensation of xanthotoxol (II, R=OH) and -cyclolavandulyl bromide (III). The synthetic product has been shown to be identical with natural iliensin.We thank Dr S.Z. Qasim and Dr M.S. Chadha for the spectral data and C.S.I.R. for a research fellowship to J.V.     

A simple synthesis of (E)-3-formylbut-2-enenitrile,and its use as a precursor of isotope-labelled zeatin and (±) dihydrozeatin

Summary (E)-3-Formylbut-2-enenitrile (4) is synthesized in 2 steps by reacting pyruvaldehyde dimethylacetal and acetonitrile in the presence of sodium methoxide, followed by acid hydrolysis to give 58% overall yield on distillation. The aldehyde4 can be stepwise and selectively reduced to (E)-3-hydroxymethylbut-2-enylamine (7a) in 37% total yield or exhaustivelyb reduced in 1 step to (±)-4-hydroxy-3-methylbutylamine (6) in 46% total yield. Compound7a and6 can be condensed with 6-chloropurine to give zeatin and (±)dihydrozeatin respectively. This provides a readily accessible method for isotope-labelled zeatin and its derivatives at side chain.Contribution No. 1064, Alberta Research CouncilProcess for the Preparation oftrans-3-formylbut-2-enenitrile S. Chen and J. MacTaggart, patent applicatioin registered in Canada and the United States of America.Acknowledgment. The author thanks Mr J. M. MacTaggart and Mrs C. M. Goulet for valuable experimental assistance and Dr R. M. Elofson for helpful discussions.     

Influence of PGA1 on cartilage growth

Summary Using the Fell technique of organ culture of cartilage in a chemically defined medium, it has been shown that prostaglandin A₁ at a concentration of 25 g/ml caused chondrocyte death in chick embryonic limb rudiments. An equimolar concentration of PGE₂ was not toxic to the cells.Acknowledgments. We are grateful for the support of C. J. K. by the Medical Research Council and of D. L. G. by the Arthritis and Rheumatism Council for Research. Our thanks are due to Dame Honor Fell, F. R. S. for invaluable advice and guidance, to Dr J. Pike (Upjohn Co.) for supplies of prostaglandin A₁, and to Dr Sylvia Fitton-Jackson for the gift of culture medium.     

DOPA in ocular pigment cells in mammalian albinotic embryos

Résumé L'épithélium ciliaire des yeux d'animaux albinos (rat, souris, cobaye, lapin) contient du DOPA (0,01–0,03µg par il de lapin) au dérnier stade du développement des embryons.

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This study was supported by grants from the Swedish Medical Research Council (projects No. B 67-12X-712-02A and B 67-14X-56-03A).     

The structure of amoorastatone and the cytotoxic limonoid 12-hydroxyamoorastatin

Summary 2 new limonoid-type terpenes have been isolated from an aqueous extract of seeds produced by the Eastern Himalayan (India) plantAphanamixis grandifolia Bl. By interpreting principally mass spectral and nuclear magnetic resonance data, the structures of 12-hydroxyamoorastatin (2b) and amoorastatone (3) were elucidated. Unequivocal evidence for the 12-hydroxyamoorastatin structural assignment was obtained by chemical conversion to sendanin (4). Amoorastatin derivative2b was found to significantly inhibit growth of the murine P388 lymphocytic leukemia cell lines but amoorastatone in the same system was inactive. In a comparative biological study, sendanin (4) and anthothecol (7) were also found significantly to inhibit growth of the P388 cell line, while rohitukin (8) and limonin (9) were found to be inactive.Part 63 of the series Antineoplastic Agents. For the previous contribution refer to G.R. Pettit, T.S. Krupa and R.M. Reynolds, Int. J. Peptide Protein Res., in preparation. The present investigation was supported in part by Public Health Research Grant No. CA-16049-05 from the National Cancer Institute, the Fannie E. Rippel Foundation, Mrs Mary Dell Pritzlaff, the Spencer T. and Ann W. Olin Foundation, Mr John F. Schmidt, and the Phoenix Coca-Cola Bottling Company.     

Imparied bone resorption of cultured calvaria from mice with abnormal lysosomal function (the Chediak-Higashi syndrome)

Summary Spontaneous bone resorption is reduced in cultured calvarial bones from mice with the Chediak-Higashi syndrome, as indicated by decreased mobilization of calcium from the bones to the medium. Although bone resorption in calvaria from mice with this disease can be stimulated by PGE₂ and 1 (OH)D₃, the amounts of mineral released after stimulation is also decreased.This investigation was supported by grants from the Swedish Association against Rheumatic Diseases, from the Royal 80 Year Fund of King Gustav V, and from the Swedish Medical Research Council (project No 14X-05426).     

Effect of testosterone and 17-β estradiol on limb regeneration in the newt,Notophthalmus viridescens

Summary Gonadectomy, or injections of testosterone or 17- estradiol, had no apparent effect on the rate of regeneration or histological appearance of limb regenerates in the newt,Notophthalmus viridescens. Neither promotion, nor inhibition of limb regeneration was observed.This work was supported by a grant from the National Research Council of Canada to S.R.S.     

Beta1-adrenoceptor mediated salivary gland enlargement in the rat

Summary In the rat, prolonged activation of ₁-adrenoceptors causes a gain in salivary gland weight, whereas prolonged blockade of these receptors causes a reduction in weight.This work was supported by grants to J.E. from the Medical Faculty in Lund and the Swedish Medical Research Council (05927).     

Nomenclature of steroidal sapogenins

Zusammenfassung Es werden Einzelheiten für den Gebrauch von Spirostan und Furostan, wenn nötig durch die Präfixe 5, 5, 25R und 25S modifiziert, für die Benennung der Steroid-Sapogenine bekanntgegeben. Diese Vorschläge sollen als formale Grundlage zur Nomenklatur gelten.

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A summary of the personal views of the authors, Presented by the authors to anad hoc Committee on Steroid Nomenclature (sponsored by the National Academy of Sciences and the National Research Council, and supported by a grant from the U.S. Air Force Office of Scientific Research) that met in Columbus, Ohio, October 13–15, (1961), under the chairmanship ofR. C. Elderfield.     

Influence of cyclic nucleotides on protein synthesis in vascular smooth muscle

Summary The incorporation of leucice-¹⁴C into protein in bovine mesenteric arteries was augmented by cyclic GMP (10^–3 M) and decreased by cyclic AMP (10^–3 M). There was no effect of 5 AMP (10^–3 M). The phosphodiesterase inhibiting drugs theophylline (10^–3 M) and papaverine (5×10^–5 g/ml) both decreased the leucine-¹⁴C incorporation.We are indebted to Mrs.Lena Burlin for hear assistance. Finacial support has been provided by the Swedish State Medical Research Council (No. 04X-101X-4498).     

Predominant expression of σ and ε globin genes in human leukemia K-562(S6) variant cell line

Summary In the human leukemia K-562(S6) cell line (a) the accumulation ofa-globin chains is low or absent, (b) -globin gene expression is correlated with expression of -chains and (c) the genes responsible for the terminal cell division are not operated within 8–12 cell cycles, while K-562 (S6) cells are fully induced to erythroid differentiation.This work was supported by grants from the Italian National Research Council (C.N.R.) G. R. is a recipient of a fellowship from the National Committee for Nuclear Energy, Rome. Address for reprint requests: R. G., Centro di Studi Biochimici, Via L. Borsari 46, I-44100 Ferrara.     

The isolation and structure of 13,18-dehydroglaucarubinone,a new antineoplastic quassinoid fromSimarouba amara

Summary An investigation of the Guyana plantSimarouba amara Aubl. (Simaroubaceae) for antineoplastic quassinoids led to isolation and structural determination of the new quassinoids 2-acetylglaucarubine (1a) and 13,18-dehydroglaucarubinone (2). The previously known 2-acetylglaucarubinone (3a) and glaucarubinone (3b) were also obtained. The new quassinoid2 was found significantly to inhibit growth of the murine lymphocytic leukemia P388.Antineoplastic agents 59. For part 58 refer to M. T. Edgar, G.R. Pettit and T.H. Smith, J. org. Chem., in preparation.Acknowledgments. We wish to thank Mr B. Septe for providing the¹³C-NMR-data. Dr Jean H. Schmidt and Miss Linda M. Lange for assistance with biological studies.—G.R. Pettit is grateful to the National Cancer Institute (performed pursuant to contract No. N01-67048 with the Division of Cancer Treatment, NCI, National Institutes of Health, Dept. of Health, Education and Welfare), Public Health Services Research grant No. CA 16049-03 from the National Cancer Institute, the Fannie E. Rippel Foundation, Talley Industries, and the Phoenix Coca-Cola Bottling Co., for partial support of this investigation.     

Responses of primary muscle spindle endings at constant or changing muscle length to variations in fusimotor activation

Zusammenfassung Statische oder dynamische-Fasern primärer Muskelspindelendigungen in den Fussextensoren der Katze wurden mit sich ändernden Frequenzen gereizt: Nur Stimulation statischer-Fasern mit steigender Frequenz bei gleichzeitiger Muskelverkürzung erhöht die Entladungsgeschwindigkeit primärer Endigungen, wie sie in physiologisch induzierten Bewegungen gesehen wird.

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

ZNS-aktive Phenylpropylamine vonCatha edulis FORSK. (Celastraceae) kenyanischer Herkunft

Summary The phenylpropylamine fraction ofCatha edulis FORSK. grown in Kenya has been investigated. The major components have been found to be (S)-(–)--aminopropiophenone (1), (+)-norpseudoephedrine (2) and(–)-norephedrine (3). Quantitative ratios of1, 2, 3 in tissues of different age are discussed.

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ZNS-aktive Phenylpropylamine vonCatha edulis FORSK. (Celastraceae) kenyanischer Herkunft

     

Interactions ofΔ 11-tetrahydrocannabinol with cannabinol and cannabidiol following oral administration in man. Assay of cannabinol and cannabidiol by mass fragmentographywith cannabinol and cannabidiol following oral administration in man. Assay of cannabinol and cannabidiol by mass fragmentography

Summary Oral administration to man of 20 mg ¹1-tetrahydrocannabinol (THC) together with placebo or 40 mg cannabinol (CBN) or 40 mg cannabidiol (CBD) gave evidence of a possible limited interaction of THC with CBN but not with CBD as indicated by average plasma THC levels. Peak CBD and CBN concentrations were similar to that of THC, viz. about 5–8 ng/ml.Supported by the Swedish Medical Research Council and grant MH-00424 from the Veterans Administration.     

The effect of reserpine on the intraneuronal vesicles of the rat vas deferens

Zusammenfassung Die Wirkung von Reserpin auf die intraneuronalen Vesikeln des Ductus deferens der Ratte wurde elektronenmikroskopisch untersucht. Es konnte festgestellt werden, dass die Granula der kleinen Vesikeln (3–600 Å Durchmesser) nach Reserpinbehandlung verschwanden, dass aber diejenigen der Grossen (8–1200 Å Durchmesser) unverändert blieben.

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This work has been supported by Research Grant (12x-715-01) from the Swedish Medical Research Council and by a grant from Stiftelsen G. och T. Svenssons Minne».     

TRH analogue with C-terminal thioamide group. Synthesis,receptor binding,TSH-releasing activity and α-MSH-releasing activity

Summary A new TRH analogue containing a C-terminal thioamide group was synthesized. This peptide was shown to have receptor-binding affinity, and TSH- as well as -MSH-releasing activities very similar to native TRH.Acknowledgments. This work was supported by the Swedish Natural Science Research Council (K-KU 3020-112) and the Polish Academy of Sciences (Research Grant No. MR I 12.1.6.1).