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Biomedical subjects

P Minard

Publications and source records attributed to P Minard.

47 records · Page 3Linked to original sources
PubMed1984

Murine immunization by cesium-137 irradiation attenuated Schistosoma mansoni cercariae.

Cesium-137, becoming a more readily available ionizing gamma radiation source for laboratory use, was shown to effectively attenuate Schistosoma mansoni cercariae for vaccine production. In parallel comparison studies with the murine model, cesium-137 attenuated cercariae consistently afforded better (P greater than 0.05) protection than did the cobalt-60 prepared vaccine. Dose-response data indicated that the optimal total irradiation with cesium-137 was between 45 and 50 Krad.

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PubMed1981

Immunization of Baboons with Schistosoma mansoni Cercariae attenuated by gamma irradiation.

Studies on the efficacy of a vaccine against schistosomiasis in young baboons (Papio anubis) disclosed that immunization with Schistosoma mansoni cercariae attenuated by gamma irradiation induced significant protection against subsequent infection with normal, viable S. mansoni cercariae. Such immunization resulted in reduced worm burdens (70 percent) and egg excretion rates (82 percent). These results support immunization as a potential method for schistosomiasis control.

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PubMed1978

Immunization of mice with cobalt-60 irradiated Schistosoma mansoni cercariae.

Parameters of immunization of mice with 60Cobalt-irradiated Schistosoma mansoni cercariae are described and related to protection against subsequent challenge infection. Such immunization was found to be dependent on dose of irradiation, number of immunizing cercariae, and number and time course of infections. Low levels of resistance were obtained with low irradiation doses, in contrast to previous studies in mice. In general, resistance increased with increasing irradiation doses, up to approximately 48-56 Kr. Maximal resistance (70-80%) was induced by a single exposure to 250-500 cercariae, irradiated at a dose rate of 2 Kr/minute to a total dose of 56 Kr, administered percutaneously 4-6 wk prior to challenge. Challenge could be delayed for at least 15 wk after immunization without a decrease in resistance. The resistance obtained was not attributable to a delayed migration of challenge worms.

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PubMed1978

Effect of immunization on migration of Schistosoma mansoni through lungs.

Schistosoma mansoni schistosomula migrate through the lungs of infected mice; peak recovery occurs 6 days following infection. When cercariae were irradiated at 60Cobalt doses of 24 to 64 Kr, the number of schistosomula recovered from lungs 6 days after infection decreased in a dose-dependent fashion. The pattern of lung migration of schistosomes irradiated at 56 Kr prior to infection was similar to that of nonirradiated schistosomes, but greatly reduced numbers were recovered. When mice were immunized by a single infection with 56 Kr attenuated cercariae 6 wk prior to challenge, the pattern of challenge migration through the lungs was altered. The number of schistosomes recovered increased rapidly between 2 and 6 days post-infection, and showed a plateau between 8 and 10 days with peak recovery occurring 10 days post-infection. This peak recovery was reduced in comparison to that of non-immunized mice, but did not account for all of the reduction observed at the adult worm stage.

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PubMed1978

Resistance of mice to secondary infection with Schistosoma mansoni. I. Comparison of bisexual and unisexual initial infections.

Mice receiving a unisexual primary infection with either sex of Schistosoma mansoni did not develop detectable resistance to reinfection. In contrast, mice receiving a bisexual primary infection developed a high degree of resistance. The number of adult worms developing from the challenge infection was reduced, relative to controls, by 72--100% at challenge times of 6 weeks or greater.

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PubMed1978

Resistance of mice to secondary infection with Schistosoma mansoni. II. Evidence for a correlation between egg deposition and work elimination.

Mice reinfected with Schistosoma mansoni 6--8 weeks after a primary infection largely or completely eliminated the second infection prior to the 7-week adult worm stage. In contrast, challenge worm counts were not lower than controls at the 6-day lung schistosomulum stage. At reinfection intervals of 12 or more weeks, worm counts were reduced at both stages. The reduction in lung schistosomulum count was proportional to the number of schistosome eggs present in the lungs, with no significant reduction being detected at any challenge time in mice free of lung eggs. Isolated schistosome eggs injected intravenously into the lungs of normal mice induced moderate to high levels of resistance to infection, while eggs injected subcutaneously or imtraperitoneally did not. It is concluded that the deposition of schistosome eggs in sites encountered by migrating schistosomula may be essential for mice to become resistant to reinfection with S. mansoni.

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PubMed1977

Proteolytic, antigenic and immunogenic properties of Schistosoma mansoni cercarial secretion material.

Schistosoma mansoni cercariae secrete preacetabular gland material in association with skin penetration. The material is heterogeneous and contains proteolytic enzyme(s) which comprise a small proportion of the total protein. We have immunized mice with cercarial secretion material in several protocols designed to induce a variety of antibody responses. The cercarial secretion material is sufficiently immunogenic to induce precipitating and reaginic antibody production. The antibodies obtained were not of the necessary quantity and/or quality to afford protection from a challenge infection.

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PubMedDate not supplied

Flexibility and folding of phosphoglycerate kinase.

Flexibility and folding of phosphoglycerate kinase, a two-domain monomeric enzyme, have been studied using a wide variety of methods including theoretical approaches. Mutants of yeast phosphoglycerate kinase have been prepared in order to introduce cysteinyl residues as local probes throughout the molecule without perturbating significantly the structural or the functional properties of the enzyme. The apparent reactivity of a unique cysteine in each mutant has been used to study the flexibility of PGK. The regions of larger mobility have been found around residue 183 on segment beta F in the N-domain and residue 376 on helix XII in the C-domain. These regions are also parts of the molecule which unfold first. Ligand binding induces conformational motions in the molecule, especially in the regions located in the cleft. Moreover, the results obtained by introducing a fluorescent probe covalently linked to a cysteine are in agreement with the helix scissor motion of helices 7 and 14 assumed by Blake to direct the hinge bending motion of the domains during the catalytic cycle. The folding process of both horse muscle and yeast phosphoglycerate kinases involves intermediates. These intermediates are more stable in the horse muscle than in the yeast enzyme. In both enzymes, domains behave as structural modules capable of folding and stabilizing independently, but in the horse muscle enzyme the C-domain is more stable and refolds prior to the N-domain, contrary to that which has been observed in the yeast enzyme. A direct demonstration of the independence of domains in yeast phosphoglycerate kinase has been provided following the obtention of separated domains by site-directed mutagenesis. These domains have a native-like structure and refold spontaneously after denaturation by guanidine hydrochloride.

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