Inhibited hormonal induction of hepatic phosphoenolpyruvate carboxykinase in poly I∶C treated mice,an endotoxin-like glucocorticoid antagonism

Summary Corticosteroid induction of mouse hepatic phosphoenolpyruvate carboxykinase was inhibited by prior injection of poly IC. Mice challenged with a lethal dose of endotoxin 4 h after administration of poly IC could not be protected by a concurrent injection of hydrocortisone.This investigation was supported by U. S. Public Health Service research grant No. AI-10087 from the National Institute of Allergy and Infectious Diseases.     

La pression intrarénale chez l'homme

Summary The intrarenal pressure has been determined in man using a needle of the lumbal puncture type connected with a mercury manometer. Preliminary results in 8 patients with various renal diseases indicate no significant difference between cases of glomerulonephritis, acute anuria, chronic pyelonephritis and normal or almost normal kidneys. Our values are comprised between 23.5 and 41.5 mm of mercury, with an average of 34 mm. A possible correlation with the mean blood pressure is suggested by our data: intrarenal pressure =0.19 mean blood pressure +9.0. In one case, renal decapsulation had no influence on the intrarenal pressure.     

Effect of lead microparticles introduced into the respiratory system of the sensitivity of mice to Pasteurella multocida infection via aerosol]

Lead microparticles, resulting from the pyrolysis of organic lead used as an anti-knock agent in gasoline, were introduced into the lungs of Mice, during a short single exposure. When 6 microgram of lead were retained in the lungs (mean value per Mouse), the phagocytic ability of the pulmonary alveolar macrophages harvested 6 and 18 hrs. later, was significantly reduced. It was observed, in the same conditions, that the resistance of Mice to experimental infection by aerosolized Pasteurella multocida, was significantly reduced. When 3 microgram of lead were retained in the lungs, there was no significant difference between control and intoxicated Mice.     

Potentiation of antifungal activity of sesquiterpene dialdehydes against Candida albicans and two other fungi.

The antifungal activity of two drimane sesquiterpene dialdehydes, polygodial (1) and warburganal (2), alone and in combination with several other substances, was examined against three fungi, Candida albicans, Saccharomyces cerevisiae and Pityrosporum ovale employing a broth dilution method. Anethole significantly synergized the activity of the two sesquiterpenoids against C. albicans and S. cerevisiae; however, it had only an additive effect against P. ovale. By contrast, two antioxidants, ascorbic acid (vitamin C) and BHA (butylated hydroxyanisole), noticeably enhanced the activity of the sesquiterpenoids against P. ovale, but had no effect against C. albicans and S. cerevisiae.     

Tetanus intoxication causes an increment of serotonin in the central nervous system

Mice injected with tetanus toxin (TTx) showed an increase of 5-hydroxytryptamine (serotonin, 5-HT) levels in the central nervous system. The increment was not uniform throughout the central nervous system. Particularly significant were the 25% and 80% increases observed, respectively, in whole brain and spinal cord. The levels of dopamine and norepinephrine remained unchanged. The subsequent studies of 5-HT turnover revealed a synthesis rate in the tetanic animals that was almost double that of controls. The degradation rate of the amine as well as the levels of 5-hydroxyindolacetic acid were unaffected.     

Tetanus intoxication causes an increment of serotonin in the central nervous system

Summary Mice injected with tetanus toxin (TTx) showed an increase of 5-hydroxytryptamine (serotonin, 5-HT) levels in the central nervous system. The increment was not uniform thoughout the central nervous system. Particularly significant were the 25% and 80% increases observed, respectively, in whole brain and spinal cord. The levels of dopamine and norepinephrine remained unchanged. The subsequent studies of 5-HT turnover revealed a synthesis rate in the tetanic animals that was almost double that of controls. The degradation rate of the amine as well as the levels of 5-hydroxyindolacetic acid were unaffected.     

Effect of lymphokines produced in a grafted system on production of prostaglandins by macrophages]

Mice peritoneal macrophages cultured in vitro release a prostaglandin-like activity as evaluated by a bio-assay using Rat stomach fundus. The prostaglandin release is greatly increased when macrophages are incubated with the supernatant of mixed lymphocyte cultures between recipient and donor of a skin allograft. This phenomenon was found in all strains of Mice tested except C3H/HeJ Mice, a strain already known for its defective responsiveness to bacterial lipopolysaccharide (LPS).     

Cytotoxicity of mouse peritoneal cells after alloimmunization]

CBA Mice were immunized by two intraperitoneal injections of 30 X 10(6) DBA/2 or C57BL/6 spleen cells at days--12 and--2. Peritoneal cell population was obtained at day zero by washing the peritoneal cavity of Mice. Adherent cells were then separated using a 2 hrs. incubation in "Falcon" plates followed by washing. This macrophage-rich peritoneal cell population was found nonspecifically cytotoxic against 51Cr labeled tumoral target cells: P815 X DBA/2 mastocytoma cells, EL4 X C57BL/L lymphoma cells and spontaneous lymphoma AKR cells (same H--2k as CBA). This adherent peritoneal cell cytoxicity was demonstrated after 24 hrs. incubation with the target cells. It was found in nonspecific combination as well as when using target cells syngeneic to the donor. These findings suggest that adherent peritoneal cell cytotoxicity could be at least partly due to macrophages and result from factor (s) released by sensitized lymphocytes in vivo in the same way as has been previously demonstrated in vitro.     

Demonstration of nucleotide pyrophosphatase and phosphohydrolase activities in normal lymphocyte of Balb/c mice and absence of these activities in YC8 tumor cells and in lymphocytes of animals with YC8 lymphoma]

Saline extraction of tumor cells from YC8 lymphoma transplanted in Balb/c Mice, of lymphocytes from animals bearing this tumor and of lymphocytes from control animals, allowed us to show important hydrolytic activities towards UDP-[(14C)]-galactose and galactose-[(14C)]-1-phosphate in normal lymphocytes. These activities disappear in lymphocytes from Mice bearing this tumor and in tumor cells themselves.     

Response of the ampullae of Lorenzini to static combined electric and thermal stimuli in Scyliorhinus canicula.

The effect of long-lasting electric currents on the Lorenzinian ampullae at constant temperatures between and 25 degrees C was investigated in the dogfish (Scyliorhinus canicula). Steady state neural impulse patterns in single afferent units were analyzed by plotting interval length histograms and computing mean values and standard deviations for currents between -100 and +100 nA. The mean values depended on temperature and on current strength; the relative standard deviations remained almost constant (ca. 20--30%). Negative currents, inserted at the orifice of the ampullary canal led to higher, and positive currents to lower, steady impulse rates in the whole temperature range investigated here. This static component of electrosensitivity again disappeared at higher currents (of 50 nA and more; electric overstimulation). The maximum static response was two orders of magnitude less than the maximum dynamic component of electroreception. The electrosensitivity depended on temperature: the ampullae were most sensitive to electric currents between 13 and 19 degrees C. The maximal neural activity at 19 degrees C was not shifted to higher or lower temperatures by electric stimulation. A constant equivalent of electric and thermal stimulation throughout the tested temperature and current range could not be found.     

Über eine Strahlenschutzwirkung von Apresolin und C. 5864-Su (2-Octahydro-1-azocynil-äthyl-guanidin)

Summary Mice exposed to a lethal total-body X-irradiation were partly protected by comparatively small doses of 1-hydrazinophthalazine (Apresoline®), and even smaller ones of [2-(octahydro-1-azocinyl)-ethyl]-guanidine (C. 5864-Su, guanethidine), administered prophylactically. On the other hand, only C. 5864-Su and reserpine, but not Apresoline, afforded protection against organic peroxide intoxication.     

Renal vascular reactivity to ATP in hyper- and hypothyroid rats

The effects of adenosine triphosphate (ATP) on the renal vasculature of isolated kidneys from control, hyper- and hypothyroid rats were characterized. ATP responsiveness was evaluated in basal tone and in raised tone (phenylephrine 10^–6 M) preparations. These responses were compared with those obtained with barium chloride or sodium nitroprusside (SNP), used respectively as nonreceptor agonists for vasoconstriction or vasodilation. In preparations at basal tone, ATP produced dose-related vasoconstriction, which was increased in hyperthyroid kidneys, and was severely attenuated in kidneys from hypothyroid rats. In raised tone preparations from control rats ATP produced a dual response: vasoconstriction at low doses, which declined with increasing doses to give way to vasodilator responses; biphasic responses were found in some kidneys. Hyperthroid kidneys showed increased pressor responses and a vasodilator response similar to those seen in kidneys from control rats. However, in hypothyroid kidneys the vasodilator response was abolished. The responses to barium chloride and to SNP were significantly increased and decreased in hyper- and hypothyroid kidneys, respectively; vasoconstrictor responses to SNP were also found in hypothyroid kidneys. Hence the abnormal responses to ATP observed in both thyroid dysfunctions may be partially explained by unspecific alterations in the contractile machinery of the renal vasculature in these kidneys. However, ATP responsiveness (vasoconstriction at low tone and vasodilation at raised tone) was more severely affected in hypothyroid kidneys, suggesting that purinergic (P_2X and P_2Y) receptor activity may be decreased in these organs.     

Structure of victorin C,the major host-selective toxin fromCochliobolus victoriae

Summary The predominant host-selective toxin fromCochliobolus victoriae, victorin C, is a peptide with an apparent mol. wt of 796, representing a cyclic array of the subunits1–6. The structure of the toxin has now been established as in16 through analysis of the degradation products generated by enzymic and non-enzymic partial hydrolysis. The presence of a hydrated aldehydo group requires for victorin C the composition C₃₁H₄₅O₁₃N₆Cl₃ with an amended mol. wt of 814, for which independent experimental support has been secured.     

Characterization of victorin C,the major host-selective toxin fromCochliobolus victoriae: Structure of degradation products

Summary Several host-selective toxins have been isolated in pure form culture filtrates ofCochliobolus victoriae. Acid hydrolysis of the major toxin, victorin C (apparent mol.wt 796), produced five fragments to which structures1–5 have been assigned. Spectroscopic techniques revealed that the toxin contains an additional subunit corresponding to6; thus all the components of victroin C are accounted for.     

Isoenzymes of some oxido-reductases in theCandida genus as a basis of species identification after electrophoresis

Zusammenfassung Nach Elektrophorese in Agargel wurden die Isoenzyme von G-6-PDH, LDH und MDH in Extrakten vonCandida albicans, C. tropicalis, C. pseudotropicalis, C. crusei undC. utilis untersucht. Es liessen sich diverse Isoenzyme von unterschiedlichem Aktivitätsgrad und wohl auch verschiedener Lage in den Isozymogrammen nachweisen, was bestimmte Schlüsse auf betreffendeCandida-Arten erlaubt.     

Über den Vitamin-B12-Gehalt von Organen verschieden ernährter Ratten

Summary Adult, male rats bred for over 10 generations on a soy meal-corn-diet had vitamin B₁₂ values of liver and kidney about 10 times lower than the controls. If the deficient ration was supplemented with 5µg/kg of B₁₂, these values were still about 1/5 of the controls. 3 weeks on the deficient diet lowered the B₁₂ levels in the livers and kidneys of previously undepleted rats to about 1/2, and a similar diet containing 0.1% of iodized casein lowered these levels to about 1/3 of the normal values but did not lower the B₁₂-concentration of organs of already deficient rats.Rats bred on the deficient diet and receiving for 1 month a supplement of 30µg/kg of vitamin B₁₂ or the stock diet with a similar B₁₂-content, had normal B₁₂-levels in livers and kidneys.     

Regression of genetically determined polycystic kidney disease in murine organ culture

Cystic kidneys from the mutant CPK strain of C57BL/6J mice were cultured in serum-free organ culture. During 120 h of incubation in chemically-defined medium, CPK cystic tubular changes underwent complete regression. Environmental factors regulate the expression of genetically determined polycystic kidney disease in this model.     

Regression of genetically determined polycystic kidney disease in murine organ culture

Summary Cystic kidneys from the mutant CPK strain of C57BL/6J mice were cultured in serum-free organ culture. During 120 h of incubation in chemically-defined medium, CPK cystic tubular changes underwent complete regression. Environmental factors regulate the expression of genetically determined polycystic kidney disease in this model.     

Dissociation between inhibition of phospholipid methylation and production of PAF-acether by rabbit platelets

Platelet-activating-factor (PAF-acether, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) is formed by and released from rabbit platelets stimulated with thrombin, with the ionophore A23187, with collagen and with the platelet-stimulating glycoprotein convulxin. We here show that 3-deazaadenosine (C3ado) and L-homocysteine (HCy), two inhibitors of platelet methylation, reduced the formation of PAF-acether and of its deacetylated product lyso-PAF-acether by rabbit platelets challenged with thrombin, under conditions where the accompanying aggregation was not significantly modified. In contrast, platelet aggregation induced by convulxin was completely and irreversibly blocked when C3ado and HCy were associated. Aggregation by thrombin was not affected by the methylation inhibitors even when ADP was scavenged and thromboxane formation was suppressed. Our results indicate that phospholipid methylation, thrombin-induced platelet aggregation and formation of PAF-acether can be dissociated. The formation of PAF-acether by rabbit platelets can be blocked by mechanisms other than inhibition of phospholipase A2, since the latter is not affected by C3ado and/or HCy.     

Inhibition of transplanted mouse tumors by heterologous transfer RNA

Summary Injections of yeast tRNA to C57BL mice decreased takes and inhibited growth of syngeneic transplanted tumors. Mice remaining free of tumors as result of this treatment failed to develop tumors after challenge with 5×10⁴ cells of the same tumor.This work was supported in part by a grant from the Stanley Johnson Foundation, Berne, Switzerland.