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.     

Absence of endotoxin-fever but not hyperthermia in Brattleboro rats

Summary I. c. v. administration of bacterial endotoxin produced a fever in the Long-Evans rat but not in the Brattleboro rat. Similar administration of arachidonic acid, prostaglandin E₂, prostacyclin, dibutyryl cAMP, norepinephrine, morphine and -endorphin caused hyperthermia in both Long-Evans and Brattleboro rats. Variable doses of exogenous arginine vasopressin (AVP) when centrally administered with endotoxin caused fever in the Brattleboro rat. It is suggested that AVP may play an important role in the production and release of endogenous pyrogen.     

Cellular localization of androgen in the brain and pituitary after the injection of tritiated testosterone

Zusammenfassung Nach Injektion von³H-Testosteron wurde mit Hilfe der Trocken-Autoradiographie eine selektive Aufnahme und Speicherung von Radioaktivität in Kernen spezifischer Neurone im Hypothalamus, in der präoptisch-parolfaktorischen Region, im Septum, im Hippokampus und in der Amygdala beobachtet. Im Hypophysenvorderlappen war Radioaktivität in den Zellkernen von Basophilen nachweisbar. Die autoradiographischen Ergebnisse unterstützen das Konzept eines doppelten Androgen-Feedbacks auf der Ebene des Zentralnervensystems und der Hypophyse.

---

---

We thank Mrs.Gerda Michalsky and Mrs.Anu Turnbull for their technical assistance. This study was supported by PHS grant No. AM1 929 to W.E.S. and a grant from the Rockefeller Foundation to the Laboratories for Reproductive Biology, Chapel Hill, North Carolina.     

The enhanced induction of metallothionein by zinc,its half-life in the marine fishPleuronectes platessa,and the influence of stress factors on metallothionein levels

Summary Intraperitoneal injection of zinc raised levels of a hepatic metallothionein-like species. Assuming that this species was metallothionein (MT) then levels were raised from approximately 20 g/g to 300 g/g in 7 days, and levels thereafter remained high for the next 4 weeks. The half-lives of the protein in liver and kidney from starved fish, measured using in vivo incorporation of³⁵S cysteine at 11°C, were approximately 27 days and 32 days respectively. The following agents failed to stimulate synthesis of MT in plaice: stress (due to catching), endotoxin, dexamethasone, cortisol and turpentine.     

Post nephrectomy increase in serum ribonuclease activity after total hepatectomy or nitrogen mustard derivatives administration

Résumé L'augmentation de l'activité de la ribonucléase du sérum, qui fait suite à la néphrectomie bilaterale chez le rat n'est pas modifiée par une évisceration préalable avec hépatectomie totale ou administration de moutardes azotées. Ces résultats indiquent que ni le foie ni les leucocytes et organes hémopoiétiques ne peuvent être considerés comme sources exclusives de cette augmentation.

---

---

Aided by grants from Conselho Nacional de Pesquisas and The Rockefeller Foundation.     

Synthese von 22,26-Imino-cholestan-Derivaten

Summary 3, 16-diacetoxy-5-pregnane-20-one and the analogue pregn-5-ene derivative have been converted into (22R, 25R)-22, 26-imino-5-cholestane-3, 16-diol. The configuration at C-22 and C-25 was determined by transformation into the known (22R, 25R)-5-solanidane-3-one. Application of the Ruschig method led to (25R)-22,26-imino-5-cholest-22(N)-ene-3, 16-diol.

---

---

Solanum-Alkaloide. XVI. Mitteilung. — XV. Mitteilung:K. Schreiber undH. Ripperger, Tetrahedron Letters Nr.27, 9 (1960).     

ω10-Lipoxygenase products of α-linolenic acid are esterified to phospholipids inHydra vulgaris

We have recently reported the occurrence of 9(R)-hydroxy-, 9(R)-hydroperoxy- and 9-keto-octadeca-10E,12Z,15Z-trienoic acids (9-HOTrE, 9-HPOTrE and 9-KOTrE) inHydra vulgaris, and their biosynthesis from -linolenic acid (-LA) through the action of an enantioselective 10(R)-lipoxygenase (10-LO). Here we describe the finding of these -LA metabolites as esters to the 2-position of phosphatidylcholine, phosphatidylethanolamine and, in trace amounts, phosphatidylinositol. Small amounts of a compound co-eluting with an authentic standard of 9(R)-hydroxy-octadeca-10E,12Z-dienoic acid, a metabolite potentially derived from the action of 10-LO on linoleic acid, were also found esterified with phospholipids. Since direct peroxidation of membrane lipids has been described, experiments were aimed at establishing whether -LA metabolite-containing phospholipids could originate, inH. vulgaris, from either spontaneous or 10-LO-catalyzed oxidation of phospholipid-bound -LA. Incubation of either unlabelled or radiolabelled PUFA-containing phosphoglycerides withH. vulgaris 10-LO did not result in their peroxidation. This suggests that -LA and LA metabolites are incorporated into glycerophospholipids after their formation by 10-LO, and that, as in mamals, membrane phospholipids may serve as a reservoir for these bioactive compounds. This is the first example in an invertebrate species of lipoxygenase products esterified to phosphoglycerides.     

Thrombospondin co-localises with TGFβ and IGF-I in the extracellular matrix of human osteoblast-like cells and is modulated by 17β estradiol

Thrombospondin (TSP) is a multifunctional glycoprotein which is synthesised by several cell types including osteoblasts, and incorporated into the extracellular matrix (ECM) of these cells. The function and regulation of TSP in bone is not clear. In this study, using a long term culture model of human osteoblast-like cells, we examined the distribution of TSP in the ECM and its modulation by added estradiol. In this model the osteoblast-like cells form a regular multilayer which continues to increase in depth up to 50 days post confluence. In the ECM of these cultures and in 19-week fetal bone, the bone markers osteocalcin and alkaline phosphatase were diffusely distributed in the matrix. In contrast, labelling for TSP was concentrated, confined to the banded collagen and its immediately adjacent ECM. This pattern of labelling resembled that of the growth factors transforming growth factor-I (TGF), and insulin-like growth factor-I (IGF-I), with which TSP label co-localised. Labelling intensities were comparable between fetal bone and the in vitro material for TSP, TGF and IGF-I. TSP label was present by 10 days post confluence, reached a maximum by 20 days, and declined slowly thereafter, a time course which was similar to that of IGF-I. Incubation of osteoblast-like cell cultures with 17 estradiol resulted in an increase in multilayer depth and a maximal 3-fold increase in TSP labeling at 30 days as well as approximately 2-fold increases for TGF and IGF-I. The dose-response relationship for these responses to estradiol treatment was biphasic with maximal increases at 10^–10 M–10^–11 M of added estradiol. Treatment with 17 estradiol produced labelling intensities that were not significantly different from controls. Studies with other cell types have suggested that TSP may be involved in modulation of growth factor activity. The similarities between TSP, TGF and IGF-I, in terms of their distribution and regulation by 17 estradiol treatment, may indicate a role for TSP in modulating bone cell proliferation and function through interaction with local growth factors.     

Unusual antimicrobial compounds fromAeollanthus buchnerianus

Using bioassay guided isolation, three novel 12 carbon polyoxygenated fatty acids and a novel abietane diterpene have been isolated from the the chloroform extract of aerial parts ofAeollanthus buchnerianus (Lamiaceae). Rigorous spectroscopic methods were used for compound identification. (Z,Z)-8-acetoxy-5-hydroxydodeca-2,6-dienoic acid and (Z,Z)-5,8-dihydroxydodeca-2,6-dienoic acid inhibited the spore germination ofCladosporium cucumerinum (both with Minimum Inhibitory Dose (MID) values of 1 g) andAspergillus niger (MID 5 and 25 g respectively). Further, they also reduced the hyphal growth ofPythium ultimum. (Z)-5-hydroxy-6,7,8-triacetoxydodeca-2-dienoic acid exhibited short term inhibition of the growth ofCladosporium cucumerinum. The novel abietane diterpenoid, (rel)-14-acetoxyabiet-7-en-18-oic acid inhibited the growth of the gram positive bacteriaBacillus subtilis, staphylococcus aureus andStreptomyces scabies (MIC values 80, 20 and 20 g ml^–1 respectively).     

“The True” in Gottlob Frege's “Über die Grundlagen der Geometrie”

In this essay, I examine the metaphysical and metalogical ramifications of Gottlob Frege's controversy with David Hilbert and Alwin Korselt, over Hilbert's Grundlagen der Geometrie. These ramifications include(1) Korselt's original appeals to general metatheoretic Deutungen (interpretations);(2) Hilbert's puzzling belief that whatever is consistent in some sense exists; and(3) Frege's semantic monist conviction that theoretical sense and reference (mathematical and other) must be eindeutig lösbar (uniquely solvable).My principal conclusions are(4) that Frege's position in (3) represented a pervasively dogmatic presumption that his newly discovered quantification theory must have a propositional metatheory (the True; the False); and(5) that this needless assumption adversely affected not only his polemic against the moderate semantic relativism of Hilbert and Korselt, but also his reception of type-theoretic ideas, and greatly facilitated his vulnerability to the sort of self-referential inconsistency Russell discovered in Grundgesetz V.These conclusions also seem to me to provide a conceptual framework for several of Frege's other arguments and reactions which might seem more particular and disparate. These include(6) his arbitrary restrictions on the range of second-order quantification, which undercut his own tentative attempts to give accounts of independence and semantic consequence;(7) his uncharacteristic hesitation, even dismay, at the prospect that such accounts might eventuate in a genuinely quantificational metamathematics, whose Gegenstände (objects) might themselves be Gedanken (thoughts); and, perhaps most revealingly(8) his otherwise quite enigmatic, quasi-stoic doctrine that genuine formal deduction must be from premises that are true.A deep reluctance to pluralize or iterate the transition from theory to meta-theory would also be consonant, of course, with Frege's vigorous insistence that there can be only one level each of linguistic Begriffe (concepts) and Gegenstände (objects). With hindsight, such an assumption may seem more gratuitous in the philosophy of language (where it contributed, I would argue, to Wittgenstein's famous transition to the mystical in 6.45 and 6.522 of the Tractatus); but its more implausible implications in this wider context seemed to emerge more slowly.In the mathematical test-case discussed here, however, such strains were immediately and painfully apparent; the first models of hyperbolic geometry were described some thirty years before Frege drafted his polemic against Hilbert's pioneering exposition. It is my hope that a careful study of Frege's lines of argument in this relatively straightforward mathematical controversy may suggest other, parallel approaches to the richer and more ambiguous problems of his philosophy of language.Niemand kann zwei Herren dienen. Man kann nicht der Wahrheit dienen und der Unwahrheit. Wenn die euklidische Geometrie wahr ist, so ist die nichteuklidische Geometrie falsch, und wenn die nichteuklidische wahr ist, so ist die euklidische Geometrie falsch.No one can serve two masters. One cannot serve truth and untruth. If Euclidean geometry is true, non-Euclidean geometry is false, and if non-Euclidean [geometry] is true, Euclidean geometry is false. Über Euklidische Geometrie [Frege 1969], p. 183.     

Changes in body temperature and circulating levels of interleukin-6 after intra-arterial injections or infusions of tumor necrosis factor α in guinea pigs

Tumor necrosis factor (TNF) is released systematically during the early phase of endotoxin induced fever. To study the effects of this cytokine in guinea pigs, 2 g TNF were intra-arterially injected as a bolus or slowly infused within 60 min. Both modes of administration induced a biphasic elevation of the animals' abdominal temperature lasting 6 h and stimulated the release of endogenous interleukin-6 (IL-6)-like activity. The second phase of the thermal response and the release of endogenous IL-6-like activity were significantly higher, when TNF was slowly infused into the animals' circulation, in spite of a transiently higher TNF-like activity after the bolus injection of TNF. Both TNF and IL-6 may therefore be regarded as candidates to trigger the febrile response in guinea pigs.     

Nouvelles contributions à la cytogénétique desMus Africains du sous-genreLeggada

Summary The author describes four new chromosome complements in the African pigmy-mice (Mus, subgenusLeggada). (1) One form from Angola has 18 metacentric chromosomes (N.F.=36) in both sexes. In contrast toMus minutoïdes minutoïdes Smith from South Africa, whose females have the same chromosome complement while the males show an acrocentric and shortY-chromosome, we have here a metacentricY. It is a confirmation of the hypothesis that theY ofM. m. minutoïdes was primarily of translocated type (TR) but lost a big intercalary segment of the autosomic arm. (2) In another species from Angola 2N=34;N.F.=36. It is the first case in the subgenus where a Robertsonian fusion occurs between autosomes before the transformation of the sex-chromosomesPR into sex-chromosomesTR. This observation is a confirmation that the complement 2N=36;N.F.=36 is the primitive one, being found in the three groups of species,minutoïdes, bufo-triton andtenellus. (3) Indeed, from Ghana, I have got specimens ofM. tenellus. We have here to deal with the primitive chromosome complement: 2N=36;N.F.=36. (4) In a sample of 12Leggada from the region of Bukawu (Congo), there are 5 and 7 . 4 show a total deletion of the short arm of theX-chromosome. In spite of the absence of X _dc -Y and of X _dc -X _dc in the sample, it is probable that neither of these complements is lethal.     

The oxidative metabolism ofα-chlorohydrin and the chemical induction of spermatocoeles

Summary -Chlorohydrin (I) is oxidatively metabolized to -chlorolactic acid (III) and oxalic acid (IV). Deposition of calcium oxalate within the renal tubules is responsible for the toxic effects of-chlorohydrin and a similar action on the epididymis or epididymal blood vessels could initiate the formation of spermatocoeles from this and other male antifertility agents.     

The use of 5-fluorocytosine and ketoconazole in the culture of the erythrocytic stages ofPlasmodium falciparum and some tumor cell lines

Summary In vitro culture systems are often contaminated by bacteria and fungi. It is therefore often necessary to supplement culture media with agents such as penicillin/streptomycin, gentamycin or amphotericin B. The latter cannot be used in the in vitro culture of erythrocytic stages ofP. falciparum, and thus anti-fungal agents have not been regularly used in this system. We describe the prophylactic use of 5-fluorocytosine (5-FC) and ketoconazole (KTZ) in tissue cultures at concentrations up to 300 and 10 g/ml respectively which have no effect on the growth ofP. falciparum (FCR-3 strain). A melanoma cell line (C32) and a line of uterine carcinoma (C41) were also unaffected by similar concentrations of 5-FC and KTZ. When dissolved in complete culture medium (RPMI 1640) with 10% human plasma, the minimum inhibitory concentration of 5-FC for a susceptible strain ofCandida remained below 2 g/ml. These experiments suggest that 5-FC (at 50 g/ml) alone or in combination with KTZ (at 1 g/ml) is a useful addition to the armamentarium of antimicrobials available to the tissue culture biologist for a variety of cell culture systems.     

Cytogénétique desLeggada: (1) La formule chromosomique deMus (Leggada)bufo Th., (2) Nouvelles données sur la délétion portant sur le bras court d'unX chezMus (Leggada)triton Th

Summary The author treats 2 topics connected with his studies on the cytogenetics of the African pigmy-mice. (1)Mus (Leggada) bufo Th. shows the primitive complement already detected in other species or subspecies (minutoides ssp ₁,indutus, tenellus, setulosus): 2N=36,N.F.=36, sex chromosomesPR. (2) The deletion of the short arm of oneX-chromosome (X _dc ) was previously observed as heterozygous mutation by 4 in a sample of 7 and 5 . A more important sample (18 , 21 ) gives the following results: 11 X-X, 10 X-X _dc , 18 X-Y. The occurrence of X _dc -X _dc and of X _dc -Y is also very improbable. It is not easy to understand how the chromosomeX _dc may persist in the population if the complementsX _dc -X _dc andX _dc -Y are lethal, which seems to result from these observations.     

The effect of steroid treatment on ovarian dehydrogenases in the rat. Histochemical study

Riassunto La valutazione istochimica delle attività 3-idrossisteroide deidrogenasica (3-HSD), glucoso-6-fosfato deidrogenasica (G-6-PD) e 20-idrossisteroide deidrogenasica (20-HSD) a livello dell'ovaio di ratte trattate per 20 giorni con progesterone, testosterone, estradiolo o con l'associazione progesterone-estradiolo, permette di rilevare che, a dosi inibenti l'ovulazione, solo negli animali trattati con estradiolo o con progesterone ed estradiolo si inibisce la comparsa dell'attività 20-HSD nei corpi lutei (C.L.) e si riduce quella 3-HSD e G-6-PD nei follicoli e nella interstiziale.     

Allozyme polymorphism and linkage disequilibrium ofAdh and α-Gpdh loci in wine cellar and field populations ofDrosophila melanogaster

Summary Over three years, theAdh and -Gpdh loci have been studied in two cellar populations ofDrosophila melanogaster and in two field populations which were each near to one of the cellars. Analyses of gene frequencies indicate that the divergence among subpopulations is greater in theAdh locus than in the -Gpdh locus. Selection for or againstAdh ^S allele acting on theIn(2L)t inversion influences of the -Gpdh alleles. This phenomenon may contribute to explain the maintenance of theAdh and -Gpdh polymorphism and of theIn(2L)t inversion.     

Zur Konstitution des Resibufogenins und Artebufogenins

Summary The structure of Resibufogenin is unambiguously shown to be 3-hydroxy-14, 15-oxido-bufadien-(20, 22)-olide on the basis of new degradation work. Artebufogenin A and Artebufogenin B are 3-hydroxy-14-15-keto-bufadien-(20, 22)-olide and 3-Hydroxy-14-14-keto-bufadien-(20, 22)-olide, respectively.     

On the host-symbiont-cycle of a leafhopper (Euscelis plebejus) endosymbiosis

Summary In the host-symbiont-cycle ofEuscelis plebejus and its bacterial symbionts each of both symbionts (a and t) appears in an infection form during the intraovarial transmission (adult female) as well as during the entrance into the mycetocytes (embryo) and in a vegetative form during the remaining time of the cycle.This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft to ProfessorK. Sander, whom I thank for helpful discussions.     

The effect of endotoxin on plasma α-aminoisobutyric acid

Summary The i.v. injection of bacterial endotoxin into dogs was found to cause a rapid increase in plasma levels of infused -aminoisobutyric acid. The findings suggest that nonmetabolic factors (tissue uptake, fluid shifts) influence amino acid distribution during endotoxemia.This investigation was supported in part by the Office of Naval Research, Contract N0001476CO132. R.E.K., Postdoctoral Fellow, supported by HL07090. Address correspondence to J.J.S.