Protein p126: a parasitophorous vacuole antigen associated with the release of Plasmodium falciparum merozoites.

The p126 protein is synthesized by P. falciparum between the 32nd and the 36th hour of the erythrocytic cycle, and is localized in the parasitophorous vacuole. It is processed when schizonts rupture and the major fragments (50, 47 and 18 kDa), which are released into culture supernatant, have been characterized using monoclonal antibodies. The 47 kDa fragment has been mapped at the N-terminus of the molecule. The portion of the protein p126 gene coding for this fragment contains 3 introns and is characterized by a sequence coding for 6 repeats of 8 aminoacids and by repeats of TCA/T-AGT coding for a polyserine sequence of 37 serines in a row for the FCR-3 strain. The 50 kDa fragment is also found in culture supernatant when merozoites are released from mature schizonts. The incubation of mature schizonts with leupeptin inhibits the release of merozoites and, in this case, a 56 kDa intermediate product is found. In those conditions, merozoites were observed free in the erythrocyte cytoplasm, the membrane of the parasitophorous vacuole being destroyed. The 50 kDa fragment can be obtained from the 56 kDa fragment by treatment with trypsin (a protease inhibited by leupeptin). Our results suggest that the processing of the 56 kDa fragment: 1) is protease-dependent, and could depend on a trypsin-like activity; 2) cannot occur after the release of merozoites because of the protease inhibitors contained in the serum; 3) does not occur before the release of merozoites, since no processed products of the protein p126 are observed in unruptured schizonts.(ABSTRACT TRUNCATED AT 250 WORDS)

Induction of protective immunity to Plasmodium falciparum in Saimiri sciureus monkeys with partially purified exoantigens.

Soluble Plasmodium falciparum exoantigens in crude culture supernatant fluids induced protective immunity against experimental falciparum malaria in Bolivian Saimiri sciureus monkeys. Susceptible squirrel monkeys were vaccinated with an aluminum hydroxide-fortified fraction purified from culture supernatants of P. falciparum Indochina I and Geneve/SGE-1 by cation-exchange (sulfopropyl-trisacryl) chromatography. Animals immunized with sulfopropyl-purified and corresponding control immunogens were challenged with whole blood containing monkey-adapted virulent organisms of the Indochina I strain. Hematological, serological, and parasitological profiles, including the appearance of crisis forms, served as potential indicators of protection. This immunogen conferred significant clinical protection of squirrel monkeys against needle challenge with the homologous Indochina I strain and a moderate degree of heterologous strain immunity.

Substrates for cold thermogenesis in thyrotoxic dogs.

The influence of thyrotoxicosis on energy supply during cold exposure was studied in normal and chronically thyroxine (T4)-treated normothermic dogs exposed to neutral (Ta,N = +25 degrees C) or cold (Ta,C = -21 degrees C) ambient temperatures. At Ta,N, T4 treatment significantly increased VO2, glucose turnover, and plasma 3-hydroxybutyrate concentration. The percentage of glucose turnover derived from alanine also increased in spite of lower alanine release. In cold, T4 treatment did not significantly modify O2 consumption, glucose turnover, or plasma alanine concentration, but plasma hydroxybutyrate, alanine clearance, and alanine conversion into glucose were significantly increased compared with control. It is suggested that in cold the main effect of thyrotoxicosis on energy supply, in addition to a trend toward lipid mobilization, is an increase in hepatic alanine extraction and conversion into glucose in the presence of lower muscular alanine delivery.

Effect of cold ambient temperature on glucose and alanine turnover in dogs.

The metabolic effects of acute cold exposure were examined in dogs exposed to either +25 degrees C (TaN) or -21 degrees C (TaC). Simultaneous infusion of D-3-3H glucose and U-14C alanine was used to measure glucose (R Glu) and alanine carbon (R Ala) turnover rates. At the two ambient temperatures the animals remained normothermic and normoglycemic throughout the experiments. Cold exposure provoked a significant increase in VO2 (X 4.5), plasma 3-hydroxybutyrate concentration (X 1.8), R Glu (X 2.3) and alanine metabolic clearance (X 1.7), while plasma alanine concentration (X 0.4) and R Ala (X 0.6) were significantly decreased. At TaN and TaC, significant direct relationships were found between R (Ala) and plasma alanine concentration, the alanine fractional turnover rate being higher at TaC than at TaN. At the two ambient temperatures, inverse relationship was found between R (Ala) and plasma 3-hydroxybutyrate concentration. These experiments indicate that in spite of increased glucose needs, acute cold exposure is accompanied by reduced alanine release. They suggest that alanine plays only a minor role in cold-stimulated gluconeogenesis in dogs.

Body composition, energy expenditure, and plasma metabolites in long-term fasting geese.

Starvation in 15 geese (mean initial body mass, m = 6.3 kg) fasting for about 40 days (mean decrease in m = 2.5 kg) was characterized by three periods. Period I (3-8 days), an adaptation period, was marked by a considerable decrease in the daily rate of change in m (dm) as well as in resting metabolic rate (RMR), and by high fat mobilization. In period II (a period of economy) the decreases in dm, RMR, and daily rate of nitrogen excretion (dne) were reduced: when expressed per unit of body mass these rates were either constant or decreased slightly. Period III, a critical period, was characterized by a rapid increase in both dm and dne that appeared when body mass had dropped to 4.7-3.2 kg. In parallel there was a greater decrease in intracellular fluid volume below 5 kg. Throughout the fast, in contrast to fasting mammals, plasma glucose and alanine concentrations were maintained at high levels (8-10 and 0.4 mM, respectively), and there was no increase in acetoacetate. However, after 20 days of fasting, plasma beta-hydroxybutyrate concentration (beta-OHB) increased to about 20 mM, while blood pH remained constant and blood PCO2 decreased. Thus, compensation for metabolic acidosis was partly attributed to respiratory alkalosis. Throughout the fast, the variations in beta-OHB were a mirror image of those for daily changes in body mass and in nitrogen excretion. This presumably reflects a hormonal change, but might also suggest a key role of beta-OHB in the control of energy expenditure and/or in regulation of body mass as well as in protein sparing.

[Changes in plasma levels of metabolites during long-term fasting in the goose]. / Evolution des concentrations de métabolites plasmatiques au cours du jeûne de longue durée chez l'oie.

In fed geese, plasma levels of glucose and alanine were 1.9 g.l-1 and 560 mumol.l-1, respectively. During a long fast (40 days), plasma glucose and alanine were maintained at a high level (1.5-1.8 g.l-1 and 370-540 mumol.l-1, respectively). Plasma level of acetoacetate was very low (40 mumol.l-1); by contrast, plasma level of beta hydroxybutyrate reached very high values (20 mmol.l-1) after about 20 days of fasting, then it decreased. Plasma levels of lactate and pyruvate decreased along the course of the fast, from 2 500 to 2 000 mumol.l-1 and 220 to 170 mumol.l-1, respectively.