Structure-activity relationship of the cardenolide,with special reference to the substituents and configurations at C-14 and C-15

Zusammenfassung Es wurden die kardiotonischen Wirkungen sechs neuer Derivate von 14-Deoxy-14H-digitoxigenin und 14-Deoxy-14-chloro-digitoxigenin auf das isolierte Froschherz untersucht, sowie die Beziehungen zwischen deren chemischen Strukturen und Wirkungen diskutiert.

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This study was supported by a research grant (No. 78 7012) from the Ministry of Education, Japan, and by a Grant-in-Aid from Tokyo Biochemical Research Foundation.     

Effect of pulsing electromagnetic fields on DNA synthesis in mammalian cells in culture

Summary DNA synthesis in Chinese hamster V79 cells was significantly enhanced when they were exposed to weak, pulsing electromagnetic fields generated by specific combinations of the pulse width (25s), frequency (10, 100 Hz) and magnetic intensity (2×10^–5 8×10^–5T). Conversely the DNA synthesis of cells in the fields at 4×10^–4 T was repressed to 80% of that in controls not exposed to the fields.This work was supported by Kaken Pharmaceutical Co., Ltd, Tokyo, Japan, and in part by a Grant-in-Aid from the Ministry of Education, Science and Culture of Japan and from the Foundation for Life Science Promotion Tokyo, Japan to I.K.     

Nerve growth factor selectively stimulates the degradation of chondromucoprotein in the embryonic cartilage in vitro

Summary Nerve growth factor specifically stimulates the degradation of chondromucoprotein in the chick embryonic cartilage cultivated in vitro, with little effect on chondromucoprotein, RNA, DNA and protein synthesis.Acknowledgment. I thank Dr Hiroshi Saito and Dr Yutaka Kasuya (University of Tokyo) for the generous gift of male mouse NGF.     

Chemical composition and distribution pattern of crystalline inorganic components in Japanese gymnosperms

Summary It was found that the distribution pattern of calcium oxalate monohydrate present in the leaves of gymnosperms growing in Japan is classified into 2 groups by the technique of the low-temperature plasma ashing method for biological tissues.Acknowledgment. The author expresses his best thanks to the staff of the Koishikawa Botanical Garden, University of Tokyo, for the donation of valuable plant materials for the present work.     

Paradoxical effect of 1-β-D-arabinofuranosyl cytosine triphosphate on bleomycin-induced unscheduled DNA synthesis in permeable sarcoma cells

Summary 1--D-Arabinofuranosyl cytosine-5-triphosphate (araCTP), an inhibitor of DNA synthesis, paradoxically enhanced unscheduled DNA synthesis (USD) induced by bleomycin in permeable mouse sarcoma cells. A greater enhancing effect of araCTP on bleomycin-induced USD was observed with lower concentrations of dCTP in the assay mixture. USD measured without bleomycin in nuclei isolated from mouse sarcoma cells was not enhanced, but inhibited by araCTP.Acknowledgments. The authors wish to thank Nippon Kayaku Co. (Tokyo, Japan) for providing copper-free bleomycin A₂. This research was supported in part by a grant from the Japan Ministry of Education, Science and Culture.     

Promotion of epithelial keratinization by N-methyl-N′-nitro-N-nitrosoguanidine in rat forestomach in organ culture

Summary The effect of N-methyl-N-nitro-N-nitrosoguanidine (MNNG) on epithelial differentiation of fetal rat forestomach was investigated in organ culture. When forestomach tissues removed from 16.5-day fetuses were treated with 5 g and 3 g of MNNG per ml for 1 h, epithelial keratinization was observed after 4 and 5 days, respectively, whereas it occurred after 6 days in control cultures. A clear dose-response relationship was found in the promotion of epithelial keratinization by MNNG.This work was supported by a Grant-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan.Acknowledgment. The authors wish to express their gratitude to Prof. T. Mizuno of the University of Tokyo for valuable suggestions.     

Differential sensitivity to ethidium bromide of replicative DNA synthesis and bleomycin-induced unscheduled DNA synthesis in permeable mouse sarcoma cells1

Summary Replicative DNA synthesis in permeable mouse sarcoma cells was more sensitive to ethidium bromide (EtBr) than bleomycin-induced unscheduled DNA synthesis (UDS). A similar difference in sensitivity to EtBr was observed between DNA polymerases and . The difference in sensitivity to EtBr of replicative DNA synthesis and UDS in the present system seems to reflect mainly the sensitivity difference between DNA polymerases and .Acknowledgments. The authors wish to thank Nippon Kayaku Co. (Tokyo, Japan) for providing copper-free bleomycin A₂. This research was supported in part by a grant from the Japan Ministry of Education, Science and Culture.     

Epithelial-mesenchymal interaction in differentiation of duodenal epithelium of fetal rats in organ culture

Summary Epithelial-mesenchymal interaction in the differentiation of duodenal epithelium of fetal rats was investigated by recombination experiments in vitro. The proportion of goblet cells in duodenal epithelium was significantly greater on recombination of developing duodenal epithelium with mesenchyme of the glandular stomach than on recombination with that of the duodenum. Mesenchyme of the glandular stomach or forestomach was better than duodenal mesenchyme in supporting morphogenesis of duodenal epithelium. Treatment of tissues with N-methyl-N-nitro-N-nitrosoguanidine (MNNG) did not affect these tissue interactions.This work was supported by grants-in-aid for cancer research from the Ministry of Education, Science and Culture, Japan.Acknowledgment. The authors wish to express their gratitude to Prof. T. Mizuno of the University of Tokyo for valuable suggestions.     

Molecular mechanism on the energy transfer and conversion in the photosynthetic system

Zusammenfassung Auf molekularer Basis wird die Energieübertragung und die Energieumsetzung in einem primären photosynthetischen System untersucht. Die Energieübertragung in den Pigmenten und im Chlorophyll-A wird mit der Energieübergangswahrscheinlichkeit und dem Diffusionsmodell eines intramolekularen «Exitons» mit Dipol-Dipol-Wechselwirkung behandelt. Bei einer Chlorophyllkonzentration von 0.1M/1 wird die Diffusionskonstante des «Exitons»D _e 1.1 × 10^–3 cm²/sec und seine Diffusionslängel _e 250 Å. Als Energieumsetzung wird die Anregung eines – -Tripletts des Chlorophyll-A mit Hilfe eines paramagnetischen Metallenzyms vorgeschlagen und diskutiert.

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This work was supported by grants from the Japanese Society for the Promote of Science. The author wishes to express his gratitude to ProfessorM. Kotani of Tokyo University and ProfessorK. Oomori and ProfessorG. Tomita for their encouragement.     

Aplysianin-A,an antibacterial and antineoplastic glycoprotein in the albumen gland of a sea hare,Aplysia kurodai

Summary Aplysianin-A, an antibacterial and antineoplastic factor in the albumen gland of the sea hareAplysia kurodai, was isolated. It had a molecular weight of approximately 320 kD and consisted of subunits with a molecular weight of 85 kD. It contained 9.8% neutral sugar. Aplysianin A showed 50% inhibition ofBacillus subtilis growth at a concentration of 4 g protein/ml and 50% lysis of murine MM46 tumor cells at 14 ng protein/ml. A partial identity of antigenic specificity of the purified specimen with an antineoplastic factor fromAplysia eggs was observed in immunodiffusion tests.Acknowledgment. We are indebted to the staff of Fisheries Research Laboratory, Faculty of Agriculture, University of Tokyo, Maisaka, for the collection of sea hares.     

Trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid) inhibits the effect of androgens on the rat prostate

Summary Trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid, FA) antagonized the effect of exogenous androgens on the ventral prostate (VP) in castrated rats as well as the effect of endogenous androgens in intact rats. FA, however, had no effect on the seminal vesicles (SV) and levator ani muscle (LAM), nor oestrogenic effect in female rats and mice. FA did not antagonize the receptor binding of testosterone nor inhibit the conversion of testosterone into 5-dihydrotestosterone (DHT).Supported in part by the project fund (grant 53-403) of Kawasaki Medical School.The authors would like to thank the Central Laboratory, Sankyo Pharmaceutical Co., Tokyo, for supplying 19-nortestosterone-17-ferulate.     

Crossing between nondiapausing and diapausing races of Sarcophaga peregrina

Summary The temperate race (D) ofS. peregrina undergoes pupal diapause in response to certain environmental conditions of photoperiod (13L:11D–11L:13D) and temperature (under 20°C). The tropical race (ND) does not do so under the same circumstances. The tendency toward diapause was suppressed in 30–40% of the hybrids of crossings D×ND and ND×D even under such short day and low temperature conditions as 11L:13D–9L:15D, 20°C. For entering diapause, the hybrids require a shorter day length (13L:11D) than that of (D) parents (15L:9D).We thank Dr R. Kano and Dr S. Shinonaga, Tokyo Medical and Dental University, for supplying the New Guinean material.     

Studies of a key protein in the mechanism of the excitation-contraction coupling process of frog skeletal muscle,using phenylglyoxal

The excitation-contraction (E-C) coupling process in single twitch fibres from frog toe muscle was inhibited selectively by phenylglyoxal (PGO), a specific guanidyl modifying reagent. A new protein (31.5 kDa), which has PGO-binding ability and seems to play a key role in the E-C coupling process, was solubilized from transverse tubule membrane-junctional sarcoplasmic reticulum complexes (TTM-JSR) of frog skeletal muscles, using¹⁴C-PGO. The monoclonal antibody against this protein applied extracellularly inhibited the E-C coupling process of the single fibres. This protein appears to constitute the very first step of input for E-C coupling. It is considered to behave as an indispensable part of an electrometer to measure membrane potentials. Therefore, the name electrometrin is suggested for the new protein.     

Changes in the activities of protein kinase modulators in the cerebellum of mice due to ethanol,caffeine, or phenobarbital administration

Summary Decreased activities of both the inhibitory modulator of adenosine 35-monophosphate (cAMP)-dependent protein kinase (A-PK) as well as the stimulatory modulator of guanosine 35-monophosphate (cGMP)-dependent protein kinase (G-PK) from the mouse cerebellum were noted due to the administration of excessive doses of ethanol, caffeine, and phenobarbital for up to 28 days. The dose-dependence of the inhibition of A-PK or the stimulation of G-PK was observed as a function of the amount of protein kinase modulators in the cerebellum of mice receiving different doses of ethanol.Acknowledgments. This work was supported by a grant (RR 08119-06-PK modulator project) from NIH, USA. J.L. Williams, T. Floyd-Jones, C.F. Duggans, D.L. Boone, and S.O. Smith were prebaccalaureate trainees of MBS program. Authors thank Dr J.F. Kuo of Emory University for encouragement in this project.     

Nature and the time course of the effect of CO2 on electroretinogram (ERG) in an arachnid

Summary Electroretinogram recorded from the median eye of the scorpion, Heterometrus fulvipes before and after exposure to CO₂ indicated that the rate of recovery of b wave to pre-CO₂ level was slow and delayed as compared to a wave. b wave may therefore have a more central origin than that of a wave, which finds corroboration in the results of the depth recording in this eye with the microelectrode.The equipment was a gift from USAFOSR to Prof. T. H. Bullock and Prof. K. P. Rao, and the work was carried out at the Department of Zoology, Bangalore University. I thank Dr R. V. Krishnamoorthy and Dr A. R. Kasturi Bai.     

Giant collagen fibres in the gonopodium of the mosquitofishHeteradria formosa,Agassiz, 1853 (Pisces,Poeciliidae)

Summary The gonopodium of the mosquitofishHeteradria formosa was studied by transmission electron microscopy. In cross-section the gonopodium shows the following structure from the outside inwards: mutilayered epidermis, basal lamina and central supporting tissue, in which vessels and nerves are embedded. At the top of the gonopodium giant collagen fibres are found, which measure up to 150 m in length and 6 m in diameter. These fibres reinforce the gonopodium.This research was supported by the Deutsche Forschungsgemeinschaft. Address for reprints: Forschungsgruppe Dermatologie der Universität Heidelberg, Im Neuenheimer Feld 324, D-6900 Heidelberg.     

The effect of caerulein on epithelial growth in the mouse gall bladder

Summary Caerulein, a synthetic decapeptide, was injected into mice in order to study its effect on DNA-synthesis activity in the gall bladder epithelium. Histoautoradiography after the injection of labeled thymidine was used. Higher labeling indices were observed at 8, 12 and 24 h after caerulein injection. These data indicate that caerulein, apart from its cholecystokinetic effects, exerts a trophic effect on the gall bladder mucosa.Acknowledgements: this work was supported in part by the Fonds voor Geneeskundig Wetenschappelijk Onderzoek and by the Algemene Spaar- en Lijfrentekas.     

Kinetics of lymphocyte division in blood cultures studied with the BrdU-giemsa technique

Summary Normal human lymphocytes were cultured for 72 h with different doses of BrdU. The analysis of metaphases processed with the BrdU-Giemsa method shows that in leukocyte cultures 3 different lymphocyte populations coexist which are able to perform 1, 2 or 3 rounds of replication in vitro. Moreover, it was concluded that 5 g/ml is the minimal dose of BrdU inducing good differentiation in the areas of sister chromatid exchanges.This work was supported by grants from the International Atomic Energy Agency, the Consejo Nacional de Investigaciones Cientificas and the Comisión de Investigaciones Cientificas.     

Migration of lymphoid cells to the bone marrow of rat following eradication of cells in DNA synthesis and in mitosis

Summary Eradication of replicating bone marrow cells of rat by means of combined administration of single doses of hydroxyurea and vinblastin is followed within 9–10 h by an inflow of lymphoid cells of extramedullary origin in the range of 13,200,000/femur. The rat bone marrow with a high content of lymphoid cells was previously shown to be concentrated in stem cells. The factor(s) which convey the information of decrease of replicating marrow cells to extramedullary sites is at present unknown.Acknowledgment. This study was supported by a grant from the Chief Scientist Office, Ministry of Health, Israel.Hydroxyurea for this investigation was given as a gift by the Squibb Institute of Medical Research, Princeton, N.J. USA, to which the authors are indebted.     

Inhibition of hepatic Na+, K+-adenosinetriphosphatase in taurolithocholate-induced cholestasis in the rat

Summary Na⁺, K⁺-adenosinetriphosphatase (Na⁺, K⁺-ATPase) activity was decreased in liver plasma membranes from rats in which cholestasis had been induced by i.v. administration of sodium taurolithocholate (5 moles/100 g b. wt). Incubation of liver plasma membranes with taurolithocholate (10–1300 M) caused significant and dose dependent reductions of Na⁺, K⁺-ATPase activity at taurolithocholate concentrations above 100 M. These findings lend support to the hypothesis that cholestasis induced by monohydroxy bile acids is at least partially the result of an inhibition of hepatic Na⁺, K⁺-ATPase activity.This work was supported by the Swiss National Science Foundation.The authors thank Mr H. Sägesser and Miss B. Schütz for technical assistance.