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Biomedical subjects

I Landau

Publications and source records attributed to I Landau.

At least 55 records · Page 3Linked to original sources

Synchronized Plasmodium yoelii yoelii: pattern of gametocyte production, sequestration and infectivity.

The chronobiology of the gametocytes of P. yoelii was studied in Percoll-glucose synchronized infection in the mouse. The gametocyte developmental cycle consisted of 4 successive stages: stage 0 maturation took 27 hours from merozoite invasion, stage 0 to stage 1 lasted 6 hours, stage I to stage II and stage II to stage III lasted 3 hours each. Stage 0 gametocytes were found to sequester in small peripheral capillaries, and the number of oocysts in mosquitoes was related to the number of stage 0 gametocytes ingested.

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The blood-stages of Plasmodium georgesi, P. gonderi and P. petersi: course of untreated infection in their natural hosts and additional morphological distinctive features.

In the blood of a Cercocebus albigena and of a C. galeritus agilis monkey, the infection with Plasmodium gonderi was found to follow its well-known chronic course; P. georgesi seemed to occur as a relapsing type of malaria parasite; P. petersi was found for only a few days and at a low level in C. albigena (end of an attack?). As shown by using polarized light, the pigment granules appeared mostly as fine dots in P. georgesi, short rods in P. gonderi and long needles in P. petersi. The three species can be distinguished by the morphological appearance of the nucleus of the young trophozoites, and also by the measurement of its surface area (Sa): small round nucleus (Sa = 0.81 +/- 0.06 microns 2) in P. gonderi, large 2-coloured nucleus (Sa = 1.43 +/- 0.21 microns 2) in P. petersi, and long crescent-shaped nucleus (Sa = 2.18 +/- 0.25 microns 2) in P. georgesi. The first colour illustrations of the blood-stages of P. georgesi are presented. The dynamics of single and mixed blood infections in primate malaria parasites are discussed, with a proposal to classify them into 3 types.

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The adjustment of the schizogonic cycle of Plasmodium chabaudi chabaudi in the blood to the circadian rhythm of the host.

Experiments were performed with P. chabaudi chabaudi to investigate the relationship between the development of the parasite and the circadian rhythm of the host. Blood was taken from a donor mouse at 10.00 hours, when it contained mainly young stages and inoculated to receptor mice, either immediately or after B hours at +4 degrees C. The inoculum was diluted in order to obtain a more or less extended prepatent period. Thus, by using successively the different mice, parasitemias could be followed during 12 days before the crisis. When parasitemias reached 1%, from day 1 (D1) to D7, depending on the dilution, the parasitic patterns were studied every 6 hours during 2 or 3 days. In mice inoculated at 10.00 hours the rhythm remained unmodified. In mice inoculated at 18.00 hours the infection was at first synchronous (from D1 to D4) but the schizogony occurred between 06.00 and 12.00 hours instead of midnight. From day 4 to day 7 the infection became asynchronous. At day 10 the normal rhythm was resumed and the schizogony occurred around midnight.

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Immunization with the malaria heat shock like protein hsp70-1 enhances transmission to the mosquito.

Mosquitoes fed on mice infected with Plasmodium yoelii after an immunization with the i72 recombinant form of the heat shock protein hsp70-1 developed significantly more oocysts than mosquitoes fed on controls. This effect was due to a marked increase in the relative numbers of gametocytes during the early stages of infection. A comparison of blood-induced and sporozoite-initiated infection showed that these gametocytes were derived from merozoites released from the liver. The stimulus for increased gametocyte production is unknown but is likely to be linked with antibody-dependent cellular cytotoxicity and associated cytokine responses.

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Stage sensitivity of Plasmodium vinckei petteri to quinine, mefloquine, and pyrimethamine.

The stage-dependent sensitivity of Plasmodium vinckei petteri to the antimalarial drugs quinine, mefloquine, and pyrimethamine was investigated using single subcurative doses and 2 different tests: a prepatency test evidencing the extension of the prepatent period according to the stage at which the drug was administered, and a patency test showing the morphological alterations of the parasites and the modifications of the parasitic pattern following drug treatment. Quinine activity was maximal when it hit the midterm trophozoite. No pigment clumping was seen and parasites developed normally until they reached the schizogonic stage when they became morphologically altered and unproductive. Mefloquine also acted on the midterm trophozoites. Parasites at this stage were killed immediately by the drug as evidenced by their degenerative appearance, and dead parasites lingered in the blood smears for at least 6 hr. However, although mefloquine was active during at least 48 hr (2 cycles), some trophozoites escaped destruction. The schizont stage was found to be the most sensitive to pyrimethamine, as previously reported for other parasite species. These results add to our previous reports showing that each drug acts preferentially on a specific stage of parasite development.

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Plasmodium vinckei vinckei and P. yoelii nigeriensis: pattern of gametocyte production and development.

The morphological evolution and the periodicity of the gametocytes of two rodent malaria species were studied in the white mouse. Experiments with Plasmodium vinckei vinckei, a highly synchronous species, showed that the production of the sexual stages was periodic and was set by the specific rhythm of the asexual stages, i.e. the time of inoculation and the duration of the cycle in the blood. The duration of gametocytogenesis from merozoite to stage 0 was approximately 30 hours, and from stage 0 to stage III, 6 hours. Plasmodium yoelii nigeriensis which normally develops asynchronously in the blood was synchronized by a Percoll-glucose gradient fractionation. Although the duration of the asexual cycle was 18 hours, gametocytogenesis from merozoite to stage 0 lasted 24 hours and 12 hours from stage 0 to stage III. Some degree of sequestration was observed in the young gametocytes.

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Postprandial lymphatic flux and malaria.

24 hours after an intra-peritoneal inoculation of frozen blood infected with Plasmodium yoelii nigeriensis, the malarial infection is non detectable in most starved mice while it is patent in mice fed 2 hours before the inoculation. It is assumed that the post feeding lymphatic flow brings to the blood the latent merozoites.

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Synchronization of Plasmodium yoelii nigeriensis and P. y. killicki infection in the mouse by means of Percoll-glucose gradient stage fractionation: determination of the duration of the schizogonic cycle.

The youngest (rings and young trophozoites) erythrocytic stages of Plasmodium yoelii nigeriensis and P. yoelii killicki, two rodent malaria subspecies developing very asynchronously in the blood, were separated from the other stages using a discontinuous Percoll-glucose gradient. They were inoculated into mice and the subsequent infection remained synchronous for two generations. The duration of the asexual cycle was found to be 18 h.

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The chemosensitivity of the rodent malarias--relationships with the biology of merozoites.

According to the hypothesis proposed by Landau, Cambie & Chabaud (1990, Annalees de Parasitologie Humaine et Comparée 65: 101-103), the chemoresistance of malaria is related to the selection of strains with latent merozoites, the latter being capable of penetrating into red blood cells at other times than that of the time of schizogony and reinfect the host with as much of a delay as several days. They determine an asynchronism of the schizogonic rhythm and, being so far resistant to all known medication, should induce, at least to some extent, a chemoresistance. Consequently, there are three factors linked to merozoites: latency, asynchronism and chemoresistance. The relationship between asynchronism and latency of merozoites has been demonstrated previously (Cambie, Landau & Chabaud, 1990, Compte Rendus de l'Academie des Sciences de Paris 310: 183-188.). In the present work it was shown that the two classifications of strains, first in order of increasing chloroquine resistance, second in order of increasing degree of persistance of merozoites in the blood, are almost identical for the 10 strains, subspecies or species of Plasmodium considered. The relationship between latency of merozoites and chemoresistance appears to have been demonstrated.

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Latency of Plasmodium merozoites and drug-resistance. A review.

The authors summarize the results of recent work evidencing the existence of latent merozoites during the course of the erythrocytic cycle of the rodent Plasmodia. These merozoites, unlike the majority of merozoites released at schizogony, do not penetrate immediately into the erythrocytes and remain latent for a variable length of time. The merozoites of each of the species or subspecies show marked peculiarities which are responsible for the characteristics of their cycle. The presence of latent merozoites free in the blood, the asynchronous development, and the resistance to chloroquine, are three closely related factors. Knowing that the merozoite is so far drug resistant, and that latent merozoites can maintain the infection for any length of time, it appears important to take into account these purely biological data, when studying the drug resistance of the human falciparum malaria.

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Plasmodium yoelii nigeriensis: biological mechanisms of resistance to chloroquine.

The sensitivity to chloroquine according to the degree of synchronicity of Plasmodium yoelii nigeriensis, which is considered to be the most resistant of the rodent malaria strains, was studied. The infection was synchronised by means of a Percoll-glucose gradient which separates rings and young trophozoites from other stages. The mid-term trophozoite, when it predominated in the blood at the time of treatment, was shown to be as sensitive to chloroquine as Plasmodium vinckei petteri. According to previous results indicating that part of the population of merozoites is latent and penetrates around midnight, the inoculations were timed in order to obtain a lower or higher degree of synchronisation. The infection appeared to be better synchronised if rings and young trophozoites, were inoculated at 06:00 hrs rather than at 15:00 hrs and consequently the efficacy of chloroquine was higher in the former than in the latter.

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Plasmodium vinckei vinckei, P. v. lentum and P. yoelii yoelii: chronobiology of the asexual cycle in the blood.

The biological rhythms of Plasmodium vinckei vinckei, P. v. lentum and P. yoelii yoelii i.e. synchronicity, duration of the erythrocytic cycle, timing of the schizogony and of the penetration of merozoites into red blood cells, were studied in the Swiss white mouse. Two different methods of synchronisation were used: the freezing-thawing of parasitized blood and the inoculation of a single parasitic stage, separated from the other stages by centrifugation through a Percoll-Glucose gradient. The duration of the schizogonic cycle of P. v. vinckei and P. v. lentum, two highly synchronous subspecies, was 24 hours. With P. v. vinckei the timing of the schizogony was independent of the circadian rhythm of the host and was set by the time of inoculation. With P. v. lentum the timing of the schizogony and merozoites penetration into red blood cells depended both, on the hosts rhythm and the time of inoculation of frozen-thawed blood: schizogony occurred at 18:00 if the inoculum was injected at 06:00 or 12:00 and at 06:00 if injected at 18:00 or 00:01. P. y. yoelii a naturally asynchronous parasite was synchronized by means of a Percoll-Glucose gradient. The duration of its intraerythrocytic cycle was found to be 18 hours, similar to that of the other subspecies of P. yoelii.

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Further description of blood stages of Plasmodium petersi from Cercocebus albigena monkey.

Additional information is given on the erythrocytic stages of Plasmodium petersi (Poirriez, Baccam, Dei-Cas, Brogan et Landau, 1933), which was found in a Cercocebus albigena monkey from the Central-African Republic. The first colour pictures of P. petersi are presented. In 60% of young trophozoites, the vacuole is divided into two or three parts by thin cytoplasmic streaks. In young trophozoites and almost mature schizonts, 80% of nuclei are oval or kidney-shaped; they are two-coloured; measurement of their surface area shows that it is about twice that of the nuclei of P. gonderi at the same stages. Studies using polarised light show that most of the pigment granules are elongated (spindle-shaped) and found at the periphery of old trophozoites and schizonts. P. petersi can easily be distinguished from P. gonderi and P. georgesi, the two other species found so far in Cercocebus monkeys, which are regarded as the African equivalents of the Asian macaques.

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In vivo antimalarial action of a lipophilic iron (III) chelator: suppression of Plasmodium vinckei infection by reversed siderophore.

We assessed in vivo antimalarial action of a lipophilic iron (III) chelator belonging to a new synthetic family of biomimetic siderophores previously termed reversed siderophores (RSFs). The family member, RSF ileum2, was chosen for its high membrane permeability and fast irreversible inhibition of human malaria parasite growth in vitro. [Shanzer A, et al., Proc Natl Acad Sci USA 88:6585, 1991 and Lytton SD, et al., Blood 81:214, 1993]. The lipophilic drug was administered to Swiss mice by subcutaneous route in fractionated coconut oil at a dosage of 0.37 g/kg every 8 hr with no adverse reactions observed. After 3-4 injections demonstrable suppression of Plasmodium vinckei petteri infection was observed and an additional 3-4 injections resulted in 2-3-fold lower parasitemia with prolonged survival time over sham-injected control mice.

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[Schizogony of Plasmodium yoelii nigeriensis. Role of latent merozoites].

Several procedures were employed to try to specify the schizogonic cycle of Plasmodium yoelii nigeriensis. The Percoll-glucose gradient technique for concentrating the very young stages (rings and young trophozoites), allowing a very precise follow up of the development of the parasitaemia during the first schizogonic cycles. A method for studying the prepatencies, providing an approximation of the number of merozoites inoculated. A comparison between the numbers of merozoites present in the blood, after--firstly simple dilutions in saline, revealing the total number of merozoites,--secondly dilutions in saline after a passage of a few hours in the organism of a mouse, revealing the number of latent merozoites. It was shown that the infection, during the first two cycles, varies according to the time of inoculation. In all cases the increase of the parasitaemia occurred mainly from 00:01 to 06:00. This increase of parasitaemia in mice inoculated with the Percoll concentrated parasites was significantly high during the first cycle in mice inoculated at 06:00 and 09:00 and during the second cycle in those inoculated at 12:00, 15:00 and 18:00. However, differences were rapidly compensated and parasitaemias became comparable at the 3rd or 4th cycle when they ceased to be dependent on the time of inoculation.

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The role of reactive nitrogen intermediates in modulation of gametocyte infectivity of rodent malaria parasites.

Direct feeding of Anopheles stephensi mosquitoes on mice infected with Plasmodium vinckei petteri showed that, during the periods of schizogony in the blood, the infectivity of gametocytes was markedly reduced. This could be prevented by prior injection of the L-arginine analogue, Nw-nitro-L-arginine (NwNLA) showing that the altered infectivity was due to reactive nitrogen intermediates (RNI). Similar effects on transmission of P. yoelii nigeriensis were demonstrated in vitro by membrane feeding of the mosquitoes. The in vitro reduction in infectivity could be reversed by injecting the L-arginine analogue either into the infected mouse donor of serum, or into the membrane feeding chamber. Elevated levels of TNF and IL-6 were demonstrated during the course of infection but did not correlate well with nitrogen radical activity. Similarly, direct measurements of NO2- and NO3- did not reflect the nitrogen radical activity revealed by addition of the specific L-arginine analogue.

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