A comparison of personality traits of gifted word learner and typical border collies.

While personality and cognition are distinct domains, some personality traits may affect the capacity for problem-solving. It was suggested that there is a positive association between the Playfulness trait and problem-solving performance in humans. Studies on giftedness (extremely good capacity in the case of a specific skill), typically aimed to reveal the genetic, experiential, and mental origins of such extreme inter-individual variation. We exploited recent findings on giftedness in a specific cognitive skill, object label learning, in dogs to explore the potential association between this exceptional skill and personality traits. We administered the Dog Personality Questionnaire to 21 gifted dog owners and compared the personality traits of their dogs to those of matched samples of 43 Hungarian and 101 Austrian typical dogs, i.e., dogs lacking this exceptional capacity. Since most Gifted Word Learner dogs are Border collies, we restricted our analysis to dogs of this breed. We hypothesized that the Gifted Word Learner dogs may show higher levels of Playfulness. As expected, we found that the gifted Border collies were rated as more playful than both the Hungarian and Austrian typical ones. Our results suggest that an extremely high level of Playfulness is associated with giftedness in a specific cognitive trait in dogs: the capacity to learn object verbal labels, thus opening new possibilities for comparative research on the relationship between giftedness and personality.

Action of chloroquine on nitric oxide production and parasite killing by macrophages.

Chloroquine is known to inhibit several functions of macrophages, but its effect on the nitric oxide (NO)-dependent parasite killing capacity of macrophages has not been documented. NO synthesis by interferon-gamma-induced mouse and casein-elicited rat macrophages was significantly and irreversibly inhibited by chloroquine. The activity of the inducible NO synthase was not directly altered, but previous incubation of macrophages with chloroquine decreased it. Chloroquine did not alter arginase activity or arginine uptake. NADPH diaphorase activity, an indicator of NO synthase was impaired. Western blotting showed that inducible NO synthase synthesis was blocked by chloroquine. The blocking of NO formation by chloroquine resulted in increased infection of mouse peritoneal macrophages by Trypanosoma cruzi (T. cruzi). This suggests that chloroquine decreases NO formation by macrophages by inhibiting the induction of NO synthase. The findings are further evidence that NO is involved in the anti-parasitic response of macrophages.

The inhibitory effect of nitrite, a stable product of nitric oxide (NO) formation, on arginase.

Macrophages contain arginase and an inducible NO synthase, demonstrated by using L-arginine, the common substrate, for production of both nitric oxide and urea. Arginase was inhibited by nitrite, the stable end product of NO. This inhibition was non-competitive, and could not be explained by the reaction of nitrite with arginine, or by the irreversible covalent modification of arginase, or by the removal of Mn2+, a cofactor of arginase.

Computer-aided comparison of the inhibition of arginase and nitric oxide synthase in macrophages by amino acids not related to arginine.

Macrophages contain arginase and an inducible nitric oxide (NO) synthase that use the same substrate, L-arginine, to produce nitric oxide and urea, respectively. Arginase was inhibited by various amino acids not related to L-arginine. These compounds were bound to the substrate binding site of the enzyme as supported by kinetic studies. Five binding sites were defined in this area by computer-aided analysis, and three complementary sites in a compound were sufficient to give an inhibitory character. NO synthase could not be inhibited by these compounds, but certain derivatives (e.g., putrescine or L-valinol) caused a marked and probably allosteric inhibition. The possible biological importance of these inhibitions in the tumoricid function of macrophages is discussed.

Formation of leucyl-leucine-O-methylester in leucine-O-methylester treated cells.

Porcine polymorphonuclear cells (PMN) and murine macrophages (M phi) were treated in vitro with Leu-OMe or Leu-Leu-OMe (1.5-5.0 mM) for various periods of time. It was found that the Leu-OMe and Leu-Leu-OMe entered cells rapidly, concomitantly the intracellular leucine accumulated. The methyl derivative diffused faster than Leucine due to its lipophylic character. The Leucine-O-methylesters hydrolysed rapidly as a consequence of the esterase and peptidase activities. The cells treated with Leu-OMe accumulated a high amount of Leucine and some Leu-Leu-OMe too. It was found that the formation of the didpeptide-methylester is not a spontaneous process, rather an enzymatic one. The Leu-OMe treated cells serve as a model which can be used to investigate the effect of the amino acid metabolism and the formation of dipeptides intracellularly and extracellularly.

Comparison of substrate and inhibitor specificity of arginase and nitric oxide (NO) synthase for arginine analogues and related compounds in murine and rat macrophages.

Arginine utilizing enzymes in macrophages showed different specificities for various arginine analogues and derivatives as substrates and inhibitors. Isolated arginase was strongly inhibited by L-canavanine(Can) and L-ornithine(Orn) but only slightly by L-homoarginine(Hom) and L-argininamide(ArgNH2). These effects were not or only weakly observed when released urea was measured in long term cell cultures. On the other hand, both L-canavanine and L-argininamide were substrates for arginase in long-term cultures. The known inhibitors of NO synthase were ineffective. The mechanisms of inhibition were different for L-canavanine and L-ornithine, but clear mechanisms could not be identified). NO synthase was studied only in long term cell cultures without purification. Certain N-guanidino (NG)-substituted arginine derivatives caused a marked inhibition while inhibitors of arginase had only slight or no effect. L-homoarginine was also found to be the substrate of NO synthase. The comparison of these effects of arginine analogues and derivatives made possible a computer-aided approximation for the fitting of active centers of these enzymes to their substrates.

Arginine supply for nitric oxide synthesis and arginase is mainly exogenous in elicited murine and rat macrophages.

L-arginine, the precursor of nitric oxide(NO) is provided mainly by extracellular sources in casein-elicited murine and rat peritoneal macrophages. Free extracellular L-arginine(Arg), esters, peptides and proteins containing Arg are the best sources in accordance with the fact that proteolytic activity is high in peritoneal macrophages. The recycling of Arg from citrulline(Cit) was observed but at a low rate. This situation is different from that in endothelial cells where half of Arg is recycled from citrulline. No significant anaplerotic reaction from glutamic acid(Glu) can be demonstrated in peritoneal macrophages.

The salvage of deoxycytidine into dCDP-diacylglycerol by macrophages and lymphocytes.

Extracellular deoxycytidine (CdR) was previously shown to be salvaged into water soluble [1] and also into lipidic [2] precursors of phospholipids in stimulated lymphocytes and in lymphoma cells [3]. In this paper we have described that non-dividing murine macrophages salvaged not only 5-3H-CdR but also tritiated thymidine (3H-TdR) mainly into the pools as nucleotides. Chlorpromazine shifted the CdR salvage into a lipidic compound of the cells which was identified as 3H-dCDP-diacylglycerol (dCDP-DAG). After 5-3H-CdR labeling the lipid/DNA ratio was eleven times higher in macrophages than in tonsillar lymphocytes. Thin layer chromatography (TLC) on borate impregnated silica gel plates gave clear separation of CDP-DAG from dCDP-DAG supporting that the extracellular precursor for it is exclusively deoxycytidine and not ribocytidine. No interconversion between deoxy- and and ribocytidine could be observed neither in lymphocytes nor in macrophages.

In vitro effect of leucine-O-methylester on polymorphonuclear and mononuclear cells.

The uptake of Leu-OMe and Leu-Leu-OMe was studied in vitro in porcine PMN cells. Both methylesters are metabolized leading to the intracellular accumulation of leucine. Part of the hydrolyzed leucine gradually filtrates back into the culture medium in a time-, temperature- and methylester substrate concentration-dependent manner. Another portion of Leu-OMe is converted to Leu-Leu dipeptide. With respect to the cellular effects of Leu-OMe treatment ultrastructural studies showed the presence of large vacuoles without significant alteration of cell viability. Increased exocytosis of lysosomal enzymes did not lead to lytic events. Changes in the plasma membrane are indicated by the observation that Leu-OMe treatment causes the loss of the chemotactic activity to formyl-Met-Leu-Phe.

Inverse relation in the de novo arginase synthesis and nitric oxide production in murine and rat peritoneal macrophages in long-term cultures in vitro.

1. The de novo synthesis of arginase was much higher in murine than in rat peritoneal macrophages. This process was inhibited irreversibly by protein synthesis inhibitors and reversibly by glycolysis blockers. 2. Rat macrophages produce more nitric oxide (NO) than murine cells. NO production was inhibited by the inhibitors of protein synthesis or glycolysis. 3. The loading of macrophages by exogenous arginine for 24 hr in vitro resulted in the increase of arginase and nitrite in macrophages to different extents. 4. No great differences in lysozyme production was observed. 5. The proportion of arginine taken up and incorporated is contrasted in murine and rat macrophages.

The effect of L-leucine methyl ester on the phagocytosis and amino acid incorporation of murine peritoneal cells.

Murine peritoneal macrophages were treated in vitro with L-leucine methyl ester (0.25-5.0 mM). This treatment resulted in an inhibition of the amino acid incorporation into the cells both at 4 degrees C and 37 degrees C during a relatively short incubation period. The adherence of macrophages was not changed by the treatment. Bacterial phagocytosis was partly influenced: Leu-OMe did not change the binding but the engulfment of opsonized bacteria was blocked. Damage of the plasma membrane caused by Leu-OMe was not so serious as that produced by specific anti-PEC antiserum. Leu-OMe is a lysosomotropic agent accumulated preferentially by lysosomes. The vacuolization of the cells and the dilatation of the vacuoles are evidences for the intracellular damage. In the early phase this damage is characterized only by the leakage of the cytoplasm, later the damage of the plasma membrane can also be demonstrated.

Stimulation of human peripheral lymphocytes with endotoxin and radiodetoxified endotoxin.

The effects of parent endotoxin and radiodetoxified endotoxin on human peripheral lymphocytes were compared in experiments in vitro. Radiodetoxified endotoxin is able to exceed the degree of the stimulation induced by parent endotoxin and its stimulatory effect. At the same time, no change was observed in the presence of autologous serum. Radiodetoxified endotoxin did not inhibit the phytohaemagglutinin-induced proliferative response.