The lymphatic route. 1) Albumin and hyaluronidase modify the normal distribution of interferon in lymph and plasma

Summary When human recombinant interferon-₂ diluted in saline was injected s.c. into rabbits, the total amount recovered in thoracic lymph was less than 0.4%. Recoveries increased from 2- to 8-fold if interferon was injected in 4% albumin or with hyaluronidase, respectively. Albumin added to interferon acts as an interstitial fluid expander, thus favoring interferon absorption through lymphatics rather than blood capillaries. This strategy may increase the therapeutic index of interferon.This work was supported by Ministero Pubblica Istruzione and Progetto Finalizzato Oncologia, contract No. 84.00461.44, CNR, Roma.     

Inhibition of neutrophil-mediated cytotoxicity by α2 macroglobulin

Summary Highly purified human 2 macroglobulin (1.2–10 mg/ml) was shown to inhibit phytohemagglutinin-induced or antibody-induced lysis of chicken erythrocytes by polymorphonuclear neutrophils. Inhibition was not associated with impaired contact between effector and target cells but rather with the antiprotease activity of 2 macroglobulin.This study was supported by D.G.R.S.T. contract No 77-7-1381.     

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).     

9-α-hydroxyparthenolide,a novel antitumor sesquiterpene lactone fromAnvillea garcini (Burm.) DC1

Summary A novel sesquiterpene lactone, 9--hydroxyparthenolide (1) was isolated from a chloroform extract ofAnvillea garcini that was collected in Iran. The structure of1 was assigned on the basis of high field NMR decoupling experiments and other spectroscopic evidence. This -methylene lactone has shown significant activity in both the 9KB cell culture and P388 mouse leukemia test systems.The authors acknowledge the support of contract No. N01-CM-97296 from the National Cancer Institute and the use of the Purdue University Biochemical Magnetic Resonance Laboratory (NIH grant No. RR01077). This is paper 16 in the series Potential Antitumor Agents.     

Scarites buparius,a caraboid beetle with an X1X2Y sex-chromosomes system

Summary Scarites buparius has 2n=37 and n=17+X₁X₂Y. This multiple sex-chromosomes system seems to be the result of a reciprocal translocation between the primitive X-chromosome and an autosome. This is the first caraboid beetle, exceptingCicindela spp., that has multiple sex-chromosomes.This work has been supported by a grant of the Comisión Asesora de Investigación Científica y Técnica, No. 1.552.     

DDT: The degradation of ring-labeled14C-DDT to14CO2 in the rat

Summary Ring fission ofp, p-DDT was studied in the rat following a single oral dose of 0.74 mg/kg (1.04 Ci) of uniformly ring-labeled¹⁴C-DDT. Expired air was passed through a solution of ethanolamine-ethylene glycol monomethyl ether (12) to trap¹⁴CO₂. A total of 1.6% of the radioactivity administered was recovered in the expired air collected continually for 10 days, indicating that while degradation of the phenyl moiety is not a major route pfp, p-DDT metabolism in the rat, it is equal to the urinary excretion. Nevertheless, these results represent the most radical change accomplished in vivo of a residual insecticide yet reported in mammals.Acknowledgment. We acknowledge the secretarial work of Ms.Elaine Smolko. This study was supported by NIH fellowship No. 1 F22 ES01723-01 and No. HL16264.     

6-Geranyloxy-3-methyl-1,8-dihydroxyanthrone,a novel antileukemic agent fromPsorospermum febrifugum Sprach var.ferrugineum (Hook. fil)

Summary A systematic fractionation of the root extract ofPsorospermum febrifugum was carried out in an attempt to reisolate the antitumor xanthone psorospermin and related compounds for further structural work and testing. This activitydirected fractionation led to the isolation of 6-geranyloxy-3-methyl-1,8-dihydroxyanthrone (1). Compound (1) was characterized based on spectroscopic and chemical evidence and showed borderline but reproducible activity in the P-388 mouse leukemia system.The authors acknowledge the support from USDA for collection of the plant material and the National Cancer Institute for support of this work under contract No. NO1-CM-97296. This is paper 15 in the series Potential Antitumor Agents.Cytotoxicity was assayed under the auspices of contract No. NO1-CM-97296. The Division of Cancer Treatment, National Cancer Institute, National Institute of Health, Bethesda, Maryland awarded support for this work.     

Rabbits infested with adultIxodes ricinus L.: Effects of mepyramine on acquired resistance

Summary The results of this work demonstrate that histamine seems to be involved in the expression of the resistance acquired by rabbits to I. ricunus. Daily treatment of animals with the H₁-antihistaminic mepyramine inhibited the effects of immunity. This observation applies to the effect of resistance on the weight of engorged ticks, the duration of the blood meal and the success of egg laying and hatching.The present work was supported by the Swiss National Fund for Research, grant No. 3.303-78. We are grateful to Dr L. Julou (Rhône-Poulenc) for a gift of mepyramine.     

Role of phospholipids in the binding activity of vasoactive intestinal peptide receptors

Summary Phospholipase digestion of rat intestinal epithelial cell membranes was performed in order to study the influence of membrane phospholipids on the binding activity of VIP receptors. Phospholipases A₂ and C strougly (ED₅₀4×10^–2 and 4×10^–1 g/ml, respectively) and rapidly reduced¹²⁵I-VIP binding to membranes whereas phospholipase D was ineffective. This suggests an important role of both hydrophobic and hydrophilic groups of phospholipids on VIP receptor binding activity.This work was supported by INSERM (CRL 827017) and the Fondation pour la Recherche Médicale Française.     

Sertoli cells of adult rats in vitro. II. Effect of different steroid precursors on estradiol 17β-synthesis

Summary The estradiol 17-synthesis by ⁴ pathway has been studied in homogenous cultures of Sertoli cells isolated from adult rat testes. The data reported clearly demonstrate that progesterone, androstenedione, testosterone and estrone induce an increase of the estradiol 17-production.This work was partially supported by grants No. 77.01322.04 and No. 77.01958.04 from the Consiglio Nazionale delle Ricerche.The excellent technical assistance of Antonio Muller and Massimo Rosati is deeply appreciated.     

Lead potentiation of endotoxin lethality in rats: Lack of effect of kininase inhibition

Summary Although lead and SQ₂₀₈₈₁ are potent in vitro inhibitors of kininase II activity, SQ₂₀₈₈₁ does not alter the sensitivity of rats to endotoxin. These results indicate that marked changes in plasma kininase activity do not contribute to endotoxin morbility and that kininase inhibition is not the mechanism whereby lead ions sensitize rats to endotoxin.This investigation was supported by the Naval Medical Research and Development Command, NNMC, Department of the Navy, Research Task No. MR041.20.01.0435. The opinions and assertions contained herein are the private ones of the author, and are not to be construed as official or reflecting the views of the Navy Department or the naval service at large.The experiments reported herein were conducted according to the principles set forth in the Guide for the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, National Research Council, DHEW Pub. No. (NIH) 74-23.     

Prostaglandin E1 induced salivary secretion

Summary PGE₁ but not PGF₂ at 500–1000 g/kg induced a slow and sparse flow from the parotid and no flow at all from submaxillary glands. Composition of PGE₁-induced parotid saliva was quite different from that evoked by any autonomic agonists. The present study suggests that PGE₁ might act directly on parotid acinar cells.Acknowledgment. This work was supported by NIDR grant DE05633. The authors wish to thank Ms Sonya Wynn for her technical assistance.     

Effect of ricin,of its subunits and of modeccin on cAMP level in Yoshida ascites cells

Summary The B chain of ricin strongly decreases the PGE₁-enhanced level of cAMP in Yoshida ascites sarcoma cells, whereas the A chain is ineffective. Modeccin does not have any effect.Acknowledgments. We thank E. Lorenzoni for preparing ricin and modeccin. The work was aided by a contract from The Consiglio Nazionale delle Ricerche, Rome, within The Piano Finalizzato Controllo della crescita neoplastica and by Pallotti's legacy for cancer research.     

Enhanced depressor reflex by stimulation of superior cervical ganglion and by propranolol

Summary The systemic depressor reflex in cats evoked by inflation of an intrasinusal balloon is enhanced by stimulation of the superior cervical ganglion and by close infusion of 20g/ml/min of (d, 1) propranolol.This work was supported by grant No. 22600-1 NIH, Heart, Lung and Blood Institute, Bethesda, MD.     

Structure revision and cytotoxicity of the germacranolide,stizolicin, fromStizolophus balsamitus (Asteraceae)

Summary The structure of the cytotoxic sesquiterpene lactone, stizolicin, reisolated fromStizolophus balsamitus (Centaurea b.) was revised to atrans, trans germacranolide (1) on the basis of simultaneous application of lanthanide shift reagent and NOE in the NMR.The authors acknowledge the use of the Purdue University Biomedical Magnetic Resonance Laboratory (NIH grant No. RR01077). Support of contract No. N01-CM-97296 and Grant No. CA-33326 from the National Cancer Institute, HHS is gratefully acknowledged. This is paper 18 in the series Potential Antitumor Agents.     

Insulin stimulation of glucose and amino acid transport in mouse fibroblasts with elevated membrane microviscosity

Summary Basal and insulin-stimulated transport of 2-deoxy glucose and of -aminoisobutyric acid in mouse 3T3 fibroblasts were modulated by increasing the lipid microviscosity of the cell plasma membrane. The kinetics indicate that the insulin effect is induced either by recruitment of new transport carriers or by reduction of the translocation activation energy.This investigation was supported by grant No.5-R01-CA-27471-02, awarded by the National Cancer Institute, Department of Health, Education and Welfare.     

Changes in intracellular pH and cell volume during the early phase of DMSO-induced differentiation of friend erythroleukemia cells

Summary Changes in intracellular pH and water volume were measured after treatment of Friend erythroleukemia cells with 1.5% DMSO. It was found that a continuous decrease in pH_i occurred, beginning 1 h after induction and a decline in pH_i of 0.18 was measured after 9 h. In addition a decline in cellular water volume, of 12% only 15 min after induction, and 23% after 9 h, was observed.11 December 1986Acknowlegments. This work was supported by the Deutsche Forschungsgemeinschaft.     

Interaction of vinblastine analogues with tubulin

Summary Studies of the interaction between vinblastine-like alkaloids and their receptor, i.e. tubulin, are reported. They shed some light on the structure-activity relationships in this medicinally important series: the configurations at C₁₄ and C₁₆ as well as the presence of the methoxycarbonyl group on C₁₆ seem to play an essential role in the determination of biological activity.This work was supported by CNRS (A.T.P. No 3232).We thank Dr D. Pantaloni for interesting discussions, Drs N. and Y. Langlois for discussions and for supplying synthetic material, and Eli Lilly Laboratories for gifts of vinblastine, vincristine and leurosidine.     

Induction of nuclear styrene monooxygenase and epoxide hydrolase in rat liver

Summary The apparent K_m and V_max of styrene monooxygenase and styrene epoxide hydrolase were determined in intact nuclear preparations from male rat liver after in vivo treatment with phenobarbital and -naphthoflavone, which are known to induce microsomal cytochrome P-450 and cytochrome P-448 respectively. Treatment with phenobarbital does not alter the apparent K_m, but greatly increases the V_max of both nuclear styrene monooxygenase and styrene epoxide hydrolase. Almost the same pattern is observed for styrene monooxygenase after treatment with -naphthoflavone, whereas the same treatment slightly increases both the V_max and K_m value of styrene epoxide hydrolase.This work was supported by the CNR (National Research Council) Contract No. 78.02864.96 within the special program Control of Cancer Growth.