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Biomedical subjects

G A Butcher

Publications and source records attributed to G A Butcher.

At least 55 records · Page 3Linked to original sources
PubMed1987

Antimalarial activity of a riboflavin analog against Plasmodium vinckei in vivo and Plasmodium falciparum in vitro.

The riboflavin analog 10-(4'-chlorophenyl)-3-methylflavin was found to have significant activity against Plasmodium vinckei vinckei when administered orally and parenterally; it was active against P. falciparum in culture. It inhibited mouse erythrocyte glutathione reductase in a dose-dependent manner. When administered orally, 5-deazariboflavin was not active in vivo although it has been shown to have activity against P. falciparum in vitro.

Administration, Oral↗
PubMed1987

Possible roles of tumor necrosis factor in the pathology of malaria.

The authors have earlier proposed that tumor necrosis factor (TNF) might contribute to the pathology of malaria. Here they report the outcome of injecting recombinant human TNF/cachectin into normal mice and others with low parasitemias (6-35%) of Plasmodium vinckei. The object was to see how precisely the pathologic features of the terminal stages of this infection could be produced, when parasitemias are 70-80%. Hypoglycemia, mid-zonal liver damage, and pulmonary accumulation of neutrophils in the pulmonary vasculature, all of which are seen in severe P vinckei infection, occurred within 4-12 hours after the mildly infected mice received TNF/cachectin. Uninfected mice were much less susceptible. TNF/cachectin also increases plasma lactate, a change seen in both the human and rodent diseases. From these findings and the recent literature on TNF/cachectin, including its detection in serum from malarial patients, it seems likely that excessive release of this monokine could account for certain of the unexplained pathologic features of human malaria.

Animals↗
PubMed1986

Structure and development of the surface coat of erythrocytic merozoites of Plasmodium knowlesi.

The surface of extracellular merozoites of P. knowlesi is covered with a coat 15-20 nm thick, made up of clusters of filaments standing erect on the plasma membrane. Filaments have stems 2 nm thick, the peripheral ends of which are complex, branching or ending in long trailing threads. Coat filaments occur on the surface of the parasite in regular rows at an early schizont stage, and persist until well after merozoite release. They are sensitive to trypsin and papain, and bind ethanolic phosphotungstate, indicating a proteinaceous nature. They are also removed by exposure to phosphate-buffered saline. Filaments bear negative charges, binding cationised ferritin throughout the depth of the coat and staining with ruthenium red. They cover the whole merozoite surface and mediate intercellular adhesion at distances of 15-150 nm, membrane to membrane. It is suggested that these filaments correspond to a major merozoite surface protein, and are important in the initial capture of red cells.

Animals↗
PubMed1986

Lamellar membranes associated with rhoptries in erythrocytic merozoites of Plasmodium knowlesi: a clue to the mechanism of invasion.

In merozoites of Plasmodium knowlesi, rhoptries have a dense substructure of fine (2.5 nm diameter) granules and short rods. These are not altered by lipid extraction, and stain with ethanolic phosphotungstate indicating a proteinaceous composition. Various types of fixation also show multilamellar whorls with a periodicity of 5-7 nm in the tips of rhoptries or extruded at the merozoite apex. In merozoites fixed during invasions of red cells, membrane continuity typically occurs between the rim of the rhoptry canal and the red cell membrane, but where this contact has apparently been lost, extensive membranous whorls and blebs are often found at the apex of the parasite. Similar structures occur at the apices of merozoites within late-stage schizonts. It is suggested that the same mechanism which generates these lamellae forms the parasitophorous vacuole by inserting membranous elements formed by the parasite into the red cell membrane, so causing its invagination. A similar mechanism may be responsible for the release of merozoites from the late-stage schizont.

Animals↗
PubMed1985

The development and ultrastructure of Plasmodium falciparum damaged in vitro by human "crisis" sera and by chloroquine.

P. falciparum malaria was cultured in vitro in the presence of sera from patients with cerebral malaria, meningitis and also after chloroquine administration. Intra-erythrocytic parasite damage was seen by light and electron microscopy. The significance of the results is discussed with relevance to non-specific immune mechanisms, and the damage induced by these mechanisms compared with that from chloroquine.

Adolescent↗
PubMed1985

Initial characterisation of a lymphocyte-derived factor that is a potent stimulator of human endothelial cell prostacyclin (PGI2) production.

Supernatants from cultured normal human peripheral blood mononuclear cells were incubated with umbilical vein endothelial cells. Prostacyclin production, lactate dehydrogenase release, and viability of the endothelial cells was measured. The supernatants caused changes in growth patterns and were potent stimulators of prostacyclin production. The source of the stimulating factor(s) was shown to be the lymphocyte sub-population. Preliminary characterization of supernatants revealed that more than one molecular species may be involved.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Non-specific immunity to Plasmodium falciparum: in vitro studies.

Peripheral blood mononuclear cells (PBM) were cultured with Plasmodium falciparum malaria for several cycles of parasite growth. Non-immune PBM inhibited P. falciparum more frequently than immune PBM. The inhibiting factor appears to be released during the first 24 hours of culture and is a non-dialysable factor, probably originating from monocytes. The relevance of these findings to in vivo immunity is discussed.

Cell-Free System↗
PubMed1979

Freeze fracture studies on the interaction between the malaria parasite and the host erythrocyte in Plasmodium knowlesi infections.

The freeze fracture technique has been used to study the internal cyto-architecture of the surface membranes of the parasite and erythrocyte in Plasmodium knowlesi infections. Six fracture faces, derived from the plasma membrane and 2 pellicular membranes, have been identified at the surface of the free merozoite. The apposed leaflets of the 2 pellicular membranes show the characteristic features of E fracture faces, a result compatible with the view that the pellicular membranes line a potential cisterna. There is evidence to suggest that there may be changes in the distribution and density of the integral proteins in the merozoite plasma membrane at invasion. Furthermore, vesicles consisting of stacked membranes occur within and around the erythrocyte invagination at invasion; it is suggested that these vesicles are released from the merozoite rhoptries. Formation of the parasitophorous vacuole is accompanied by dramatic changes in the density and distribution of intra-membraneous particles (IMP) in the vacuolar membrane. Initially there is a great reduction in particle numbers, but subsequently the particles reappear and show reversed polarity. The possible causes and implications of these changes are discussed. The intra-erythrocytic parasite synthesizes new transmembrane proteins as development proceeds, and the trophozoite and schizont stages of development are characterized by the appearance of circular, particle-free regions in the parasite plasmalemma. There is a decrease in the density of transmembrane proteins in the erythrocyte plasma membrane during parasite maturation, and the P face IMP show the characteristic features of aggregation.

Animals↗
PubMed1979

Factors affecting the in vitro culture of Plasmodium falciparum and Plasmodium knowlesi.

Plasmodium falciparum and Plasmodium knowlesi have been established in continuous culture using the basic method of Trager & Jensen. Various parameters of the culture system have been examined, namely, the gas requirements, serum and red cell requirements, frequency of medium replacement, and a comparison of static and agitated cultures made. The most important factors affecting growth in vitro seem to be the oxygen tension, red cell concentration, the frequency with which old medium is replaced, and the use of appropriate sera. Preliminary results indicate that horse serum may be possible as a replacement for human serum. Initial studies with P. knowlesi indicate that in the course of adapting to culture, parasites may change their antigenic specificity.

Animals↗
PubMed1978

Antibody mediated mechanisms of immunity to malaria induced by vaccination with Plasmodium knowlesi merozoites.

Rhesus monkeys vaccinated with merozoites in FCA are protected against challenge with several strains and variants of Plasmodium knowlesi. Vaccination induces sterilizing immunity which is species specific. Merozoite-blocking (inhibitory) antibody usually correlates with clinical immunity and protection can be passively transferred with immune sera provided these contain high levels of inhibitory antibody. However, vaccination using adjuvants other than FCA may induce inhibitory antibody without clinical protection. In addition, vaccinated animals may become susceptible to challenge 4-5 weeks after splenectomy, although inhibitory antibody levels are not reduced. These observations indicate that immunity induced by merozoite vaccination involves: (i) merozoite blocking (inhibitory) antibody, (ii) specific antibody or immune complexes acting synergistically with cytotoxic splenic cells stimulated by FCA.

Animals↗
PubMed1977

Merozoite vaccination of douroucouli monkeys against falciparum malaria.

Erythrocytic merozoites of Plasmodium falciparum (Gambia) were isolated from cultures of schizont-infected human red cells on CF 11 cellulose columns. Douroucouli monkeys vaccinated with such preparations stored in liquid nitrogen and then emulsified in Freund's complete adjuvant (F.C.A.), were resistant to successive challenges with West African (Lagos) and East African (Uganda Palto-Alto) strains of P. falciparum. The induced immunity is specific since vaccination with P. knowlesi merozoites in F.C.A. does not modify the course of P. falciparum infections in douroucouli monkeys.

Animals↗