Formation of 4-ketocyclophosphamide by the oxidation of cyclophosphamide with KMnO4

Zusammenfassung Oxydation des (³²P) Cyclophosphamides durch KMnO₄ in Wasser oder Aceton führt zu 4-Ketocyclophosphamid und einem N-dechloroäthylierten Derivat des Cyclophosphamides, beides bekannte Metaboliten der Droge. Die Auftrennung der Produkte gelingt durch Dünnschichtchromatographie und die Richtigkeit der Strukturen wurde durch Massenspectrometrie nachgewiesen.

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Acknowledgments. This investigation was supported by grants to the Chester Beatty Research Institute (Institute of Cancer Research: Royal Cancer Hospital) from the Medical Research Council and Cancer Research Campaign. The A.E.I. MS-12 mass spectrometer was purchased on a special grant No. G969/189/C from the Medical Research Council. The work was carried out partly during the tenure of a Ludwig Fellowship awarded by Cancer Research Institute. The interest of ProfessorA. B. Foster and Dr.T. A. Connors in this work, and the skilled technical assistance of Mr.M. H. Baker, are gratefully acknowledged.     

A highly active glutathione peroxidase in red blood cells of normal and acatalasemic mice

The activities of catalase (E.C.1.11.1.6) and glutathione peroxidase (E.C.1.11.1.9) were compared in red blood cells from humans, ducks and normal and acatalasemic mice. In the cells from both strains of mice, an equally high activity of GSH-Px was found which could be inhibited completely by iodoacetate but was not sensitive to N-ethylmaleimide.     

Effect of synthetic polynucleotides on the growth of transplantable tumours in BALB/c mice

Summary The effect of BALB/c mice pretreatment with tumour cells (a mammary adenocarcinoma, ADK-1t and an IgA secreting plasmocytoma, MOPC-315) adsorbed with poly I:C, poly I and poly C is examined. Only mice pretreated with cells of both tumours adsorbed with poly I:C and poly C proved to be extensively protected against challenge by homologous untreated tumour cells, whereas this was not so in the case of poly I. A possible explanation of this phenomenon is discussed.This work was supported by a research contract with the Italian National Research Council (C.N.R.).     

Small lymphocyte production and lymphoid cell proliferation in mouse bone marrow

Summary In mice given³H-thymidine systemically during temporary circulatory occlusion of one hind limb, comparison of the labeling of rapidly-renewing small lymphocytes in the tibial marrows demonstrated that these cells were locally produced. Labeling by³H-thymidine infusion revealed that many marrow large lymphoid cells, presumptive small lymphocyte progenitors, had a marked proliferative activity and rapid turnover which varied according to cell size, was maximal in young mice and declined with increasing age.This work was supported by a grant from the Medical Research Council of Canada. The technical assistance of Mrs E. D. Watson is acknowledged.     

Splenic B-cell activation in lipopolysaccharide-non-responsive C3H/HeJ mice by lipopolysaccharide ofPorphyromonas gingivalis

Porphyromonas gingivalis 381 lipopolysaccharide (LPS) definitely exhibited mitogenic activity in purified B-cells, separated from spleens of LPS-responsive C3H/HeN mice and LPS-non-responsive C3H/HeJ mice by using a magnetic cell sorting system. The mitogenic activity induced byP. gingivalis LPS was incompletely inhibited by polymyxin B.P. gingivalis LPS also induced a higher production of interleukin-6 (IL-6) in splenic B-cells of C3H/HeN mice as compared withEscherichia coli LPS. Furthermore,P. gingivalis LPS, but notE. coli LPS, induced definite IL-6 production in C3H/HeJ mice.P. gingivalis LPS increased tyrosine, serine/threonine phosphorylation of proteins with various major induced bands in splenic B-cells of both C3H/HeN and C3H/HeJ mice. Additionally, radioiodinatedP. gingivalis LPS, similarly toE. coli LPS, bound to a 73-kDa protein on C3H/HeJ as well as C3H/HeN B-cells. ThusP. gingivalis LPS may activate B-cells of C3H/HeJ as well as C3H/HeN mice via the LPS-specific binding protein on the cells.     

Isolation of intracellular yolk granules in early chick embryos and estimation of their DNA content

Zusammenfassung Nachweis, dass der DNS-Gehalt der Dottergranula in Hühnerembryonalzellen in der frühesten Entwicklungsperiode (0–18 h) temporär ansteigt.

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The scanning electron microscope was made available by Analytica, Sollentuna and the scanning micrograph was taken by Mr.G. Alsterborg.

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This work has been supported by the Swedish Natural Science Research Council (H.E.) and Kungliga Fysiografiska Sällskapet, Lund.     

Induction of brain tumours in high yield by administration of N-ethyl-N-nitrosourea to newborn rats

Zusammenfassung Durch einmalige Verabreichung von 10 mg/kg N-Äthyl-N-Nitrosoharnstoff am 1. Tag nach der Geburt wurden bei 33/34 Ratten 53 Hirntumoren, 9 Tumoren des Rückenmarkes, aber nur 9 im peripheren Nervensystem erzeugt, was eine bedeutend gesteigerte Rate von Hirntumoren bedeutet.

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We thank MissMary Trumper and MissValerie Nash for technical assistance and the Cancer Research Campaign for financial support of C.E.S.     

Short-term and long-term radioprotective effect of magnesium pemoline

Zusammenfassung Magnesium-Pemoline, ein mildes Reizmittel für das Nervensystem, hat sich als gutes Strahlenschutzmittel für kurze oder lange Zeitdauer erwiesen. Für den Schutz über eine kurze Zeitdauer ist die Wirkung abhängig von der Arzneimitteldosis, für denjenigen über eine längere Zeitdauer (bis zu 2 Wochen) ist jedoch eine sehr hohe Dosis (75 mg/kg) notwendig.

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This work was supported in part by Grant No. 2 44 33 90 3 06 from the Norval Pierce Research Fund, University of Illinois and in part by a grant from Abbott Laboratories.     

Adenosine deaminase activity in peripheral blood cells from SJL/J mice

Summary Adenosine deaminase (ADA) activities were measured in peripheral blood cells of SJL/J mice, and compared with those of C57BL/6J animals. No association was observed between the levels of lymphocyte or erythrocyte ADA and immunologic abnormalities in SJL/J mice nor was evidence obtained to suggest a relationship between ADA activity and tumorigenesis in this strain.This work was supported in part by a University College Faculty Research Grant.     

Inhibition of secretion and secretory potentials in the submandibular gland of the cat by acetazolamide

Zusammenfassung Es wird eine Hemmung der Speichelflussrate in der Submandibularisdrüse der Katze durch den Kohlensäureanhydratasehemmstoff Acetazolamid hervorgerufen und gleichzeitig eine Hemmung der sekretorischen Potentialunterschiede über Azinuszellmembrane gemessen. Die Sekretionshemmung liesse sich durch die Hemmung der sekretorischen Potentiale, die ein Mass für einen aktiven Anionentransport ist, erklären.

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We are greatly indebted to Dr. N. A.Thorn for his valuable help and criticism throughout this study.

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The work was supported by a grant from the Danish State Research Foundation. — We thank Dr. C.Crone for loan of various equipment supplied by the F. L. Smidth Foundation and the Danish State Research Foundation.     

The delta sleep inducing peptide (DSIP). Comparative properties of the original and synthetic nonapeptide

Summary Both the original and the synthetic nonapeptide Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu enhance, in recipient rabbits, spindle and delta EEG activity as in orthodox slow wave sleep.Acknowledgment. This work was supported by grants from the Swiss National Foundation for Scientific Research (No. 3.871.72, 3.527.75,3.443.074, 3.780.076), Fonds für Lehre und Forschung der Universität Basel, Merck Sharp and Dohme (USA), Ciba-Stiftung Basel, Hoffmann La Roche Ltd Basel, Sandoz Ltd Basel. We received valuable help from Dr S. Roncari, Dr B. Wilson and Dr C. D. Bennett for chemical research, and from Prof. A. Cerletti, Dr H. J. Tobler and Mr J. J. Regez (Division of Application and Research Development, Sandoz Ltd) for data processing.     

Plasma hormone levels in normal and lead-treated pregnant mice

Summary Dietary lead (0.5%) was given to mice which, after mating, exhibited a vaginal plug. Estradiol, progesterone and prostaglandins E and F 2 were determined in, the plasma by radioimmuno assay at different times thereafter. The increase in estradiol and decrease in prostaglandins prior implantation are not greatly altered by lead treatment, whereas the subsequent increase in progesterone and later in estradiol is abolished. It is concluded that the lower number of pregnancies seen in lead-treated mothers is due to a maternal hormonal imbalance caused by lead.Supported by contract 038-74-7 ENV B of the E.C. Environmental Research Program. Publication No. 1394 of the Euratom Biology Division.     

Evaluation of the maternal role in survival of suckling mice

Zusammenfassung Das Überleben der von der eigenen Mutter und von stammesfremden «Ammen» gesäugten Jungen wurde untersucht an Mäusen der Stämme AKR/Sp, PL/Sp und C57BL/Sp. Die Ergebnisse zeigen, dass die genetische Herkunft der Säuglinge wie auch andere, nicht genetisch bedingte Einflüsse der Mutter auf die Jungen in utero für das Überleben der Jungen ausschlaggebend ist.

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This investigation was supported in part by Public Health Service Research Grants Nos. CA 02151, CA 02903 and CA 02624 from the National Cancer Institute, and in part by an institutional grant to the Detroit Institute of Cancer Research from the United Foundation of Greater Detroit allocated through the Michigan Cancer Foundation.     

Sulfhydryl groups,copper, diphenylamine reaction and some enzymes in the serum of rats with 6-sulfanilamidoindazole arthritis

Zusammenfassung Bei oraler Gabe von täglich 125 bzw. 250 mg/kg 6-Sulfanilamidoindazol zeigten am 9. Tag 93% der Ratten Arthritis der hinteren Extremitäten. Im Serum waren Sulfhydrylgruppen um 40% abgesunken, Kupfer um 82% und Diphenylaminreaktion um 55% angestiegen. Die Fermente Lysozym, LDH, LAP und GOT sowie die Entzündungseinheiten blieben unbeeinflusst.

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Acknowledgments. 6-SAI was kindly supplied by Mr.Z. E. Mielens, Sterling Winthrop Research, Institute, Rensselaer, USA, and Prof. Dr.E. Hannig and Mr.C. Kollmorgen, Sektion Pharmazie, Halle. We thank Mrs.R. Wangemann for skilful technical assistance.     

The in vitro effect of aprotinin upon spleen cells from normal and tumour-bearing mice exposed to PPD and tumour cells

Summary A protinin (Trasylol) is shown to enhance the response of spleen cells from normal and tumour bearing mice to PPD and tumour cells. This enhancement is greater in the tumour-bearing mice.Acknowledgments. We are grateful to Bayer (U.K.) Limited for generous supplies of aprotinin. The PPD was supplied by the Ministry of Agriculture. The work was supported by a grant from the North of England Cancer Research Campaign.     

Biological and pharmacological significance of the expanded S-outer shell in electron transfer reactions

Zusammenfassung Die Dihydrosulfoxidgruppe wird als potentielle Wirkungsgruppe für die Photolyse von Wasser zur Diskussion gestellt. Die Möglichkeiten der Elektronenübertragung von Cytochromdihydrosulfoxid werden erwogen.

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The author received the primary inspiration for this study during a Research Fellowship with Dr.M. Calvin of the Lawrence Radiation Laboratory at the University of California in Berkeley. Further assistance of Dr.J. A. Bassham of the Berkeley Group is appreciated. Thanks are also due to Drs.L. A. Strait, L. D. Tuck, andE. C. Jorgensen of the School of Pharmacy at the U.C. Medical Center, San Francisco, for discussions and assistance during the writing of this paper.     

Tris as a blocking agent of the proton-sensitive component of the sodium efflux in barnacle muscle fibers

Zusammenfassung Studien über den Natriumtransport in den Muskeln vonBalanus sp. haben bewiesen, dassTris den protonempfindlichen Anteil der Natrium-Pumpe verlangsamt und dasTris hauptsächlich an der Aussenseite des Sarkolemms aktiv ist.

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Acknowledgments. This work was supported in part by grants from the Wisconsin Heart Association, the Medical School Research Committee, the Graduate School Research Committee and the Office of Naval Research. Our thanks are due to Mr.Geoffrey Chambers for technical assistance. E.Y.T. is a Postdoctoral Fellow of the Wisconsin Heart Association. B.G.D. is a Visiting Scientist of the American Heart Association.     

Morphological and enzymehistochemical changes in the interscapular adipose tissue of adult guinea-pigs during prolonged exposure to cold

Zusammenfassung Dauereinwirkung von Kälte (2 Monate +4°C) führte beim Meerschweinchen zum Auftreten multilokularer Fettzellen, welche intensive histochemische Reaktion für mehrere oxydative Enzyme zeigten. Die Zahl der Mitochondrien und LDH-1 war im Kälteversuch vermehrt.

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Acknowledgment. This study was initiated when Dr.J. Hirvonen worked as a post-doctoral fellow of NIH, U.S. Public Health Service (No. F05 TW 1546) at Arctic Health Research Center, Fairbanks (Alaska).     

Mitogenicity of autolysates ofTrypanosoma congolense

Summary Autolysates ofTrypanosoma congolense, in subcytotoxic amounts, were found to be highly mitogenic in vitro for the spleen cells of normal mice. Significant amounts of [³H]-thymidine were also incorporated by the responding spleen cells of nu/nu (athymic) mice. In contrast, the spleen cells of cyclophosphamide-treated mice were unresponsive. The findings suggest that a potent B-cell-mitogen is generated by the autolysingT. congolense organism.Acknowledgments. This investigation was supported by the International Development Research Centre, Canada.     

The effect of temperature variation on spontaneous potential production from explants of brain tissue in culture

Zusammenfassung Bei zwei verschiedenen Explantaten von Telencephalogewebe 14tägiger Hühnchenembryonen ergab sich als Temperaturabhängigkeit der Aktionspotentiale: Frequenz und Amplitudenabnahme bei sinkender, Zunahme bei steigender Temperatur bis zwischen 37 und 42,5°C. Weitere Temperatursteigerung bringt die Potentiale nach stetiger Verkleinerung bei 47°C schliesslich zum Verschwinden.

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This research was supported by a grant from the Office of Naval Research, U.S. Navy Contract NONR 1598(04).