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Biomedical subjects

G Pasvol

Publications and source records attributed to G Pasvol.

At least 73 records · Page 4Linked to original sources
PubMed1990

Unrestricted growth of Plasmodium falciparum in microcytic erythrocytes in iron deficiency and thalassaemia.

The mechanism(s) underlying the apparent resistance to malaria in certain inherited red cell disorders and iron deficiency anaemia remain poorly understood. The possibility that microcytic erythrocytes might inhibit parasite development, by physical restriction or reduced supply of nutrients, has been considered for many years, and never formally investigated. We sought to determine whether in vitro growth studies of P. falciparum could provide evidence to suggest that small red cell size contributes to malaria resistance in those red cell disorders in which microcytosis is a characteristic feature. Invasion and development of P. falciparum in iron deficient red cells (mean values for mean cell volume [MCV] 66 fl, mean cell haemoglobin [MCH] 19 pg) and in the red cells of two gene deletion forms of alpha-thalassaemia (mean MCV 71 fl, MCH 22 pg) were normal, assessed both morphologically, and by 3H-hypoxanthine incorporation. Although parasite appearances were normal in all cell types, morphological abnormalities were noted in iron deficient and thalassaemic cells parasitized by mature stages of P. falciparum, notably cellular ballooning and extreme hypochromia of the red cell cytoplasm. Using electron microscopy, the red cell cytoplasm in parasitized thalassaemic cells showed reduced electron density and abnormal reticulation. Normal invasion rates were observed following schizogony in microcytic cells of both types. Our findings indicate that whilst minor morphological abnormalities may be detected in parasitized iron deficiency and thalassaemic erythrocytes, development of P. falciparum in these conditions is not limited by small erythrocyte size.

Anemia, Hypochromic↗
PubMed1989

Red cell deformability and invasion by malaria parasites.

Malaria parasites enter red cells in a multi-step process involving attachment, membrane deformation, invagination and encapsulation. The molecular basis of red cell rigidity is examined by Geoff Pasvol and lain Wilson, and they discuss its effect on the efficiency of invasion by various Plasmodium spp.

Journal Article↗
PubMed1989

Inhibition of malarial parasite invasion by monoclonal antibodies against glycophorin A correlates with reduction in red cell membrane deformability.

The effect of well-characterized monoclonal antibodies to red cell surface molecules on the invasion of human red cells by the malarial parasites Plasmodium falciparum and Plasmodium knowlesi was examined. Antibodies to glycophorin A (GP alpha) inhibit invasion for both parasite species, and this is highly correlated with the degree to which they decrease red cell membrane deformability as measured by ektacytometry. This effect on rigidity and invasion was also seen with monovalent Fab fragments. The closer the antibody binding site was to the membrane bilayer, the greater was its effect on inducing membrane rigidity and decreasing parasite invasion. Antibodies to the Wright determinant in particular were the most inhibitory. This differential effect of the various antibodies was not correlated with their binding affinities or the number of sites bound per cell. Antibodies to surface molecules other than GP alpha were without effect. A novel mechanism is described whereby monoclonal antibodies and their Fab fragments directed at determinants on the external surface of red cells might act to inhibit invasion by malarial parasites by altering membrane material properties.

Animals↗
PubMed1988

Genetic factors as determinants of infectious disease transmission in human communities.

Genetic factors may play an important role in individual susceptibility to infection. Hitherto this problem has been investigated by attempting to relate the distribution of genetic polymorphisms in populations to present or past infection, or by analysing specific infections by classical twin studies or group comparisons. There is reasonable evidence that the common red-cell polymorphisms involving haemoglobin, enzymes or membrane have been maintained by relative resistance to malaria. Blood-group heterogeneity, including secretor status, may reflect varying susceptibility to bacterial, virus and yeast infection. There is increasing evidence that the HLA-DR system may be involved in modifying the clinical course of bacterial, virus and parasitic infection. So far no specific resistance or susceptibility loci similar to those found in murine models have been found in man. DNA analysis, particularly involving restriction fragment length polymorphism associations with candidate genes, offers a valuable new approach to this problem.

Communicable Diseases↗
PubMed1987

Cardiorespiratory arrest and autonomic neuropathy in AIDS.

Four of five patients with AIDS and pulmonary infection had syncopal reactions as a result of fine-needle aspiration of the lung; in one patient the reaction was fatal. Subsequently, in one of these patients and four further patients with AIDS or human immunodeficiency virus (HIV) infection, the autonomic nervous system proved to be abnormal. This preliminary evidence suggests HIV infection may be associated with an autonomic neuropathy, which may expose these patients to particular risk after invasive procedures.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Falciparum malaria parasites invade erythrocytes that lack glycophorin A and B (MkMk). Strain differences indicate receptor heterogeneity and two pathways for invasion.

To determine the ligands on erythrocytes for invasion by Plasmodium falciparum, we tested invasion into MkMk erythrocytes that lack glycophorins A and B and enzyme-treated erythrocytes by parasites that differ in their requirement for erythrocyte sialic acid. The 7G8 strain invaded MkMk erythrocytes and neuraminidase-treated normal erythrocytes with greater than 50% the efficiency of normal erythrocytes. In contrast, the Camp strain invaded MkMk erythrocytes at 20% of control and neuraminidase-treated normal erythrocytes at only 1.8% of control. Invasion of MkMk erythrocytes by 7G8 parasites was unaffected by treatment with neuraminidase but was markedly reduced by treatment with trypsin. In contrast, invasion of MkMk cells by Camp parasites was markedly reduced by neuraminidase but was unaffected by trypsin. We conclude that the 7G8 and Camp strains differ in ligand requirements for invasion and that 7G8 requires a trypsin sensitive ligand distinct from glycophorins A and B.

Animals↗
PubMed1986

Frequency of severe neutropenia associated with amodiaquine prophylaxis against malaria.

6 out of 7 patients with severe neutropenia associated with the use of amodiaquine for malaria prophylaxis amodiaquine (400 mg weekly) plus proguanil (200 mg daily); 1 of these patients had also taken cotrimoxazole and another had taken sulphaguanidine. The 7th patient had taken amodiaquine alone, but at a higher dose. A retrospective analysis suggests that the frequency of severe neutropenia complicating amodiaquine taken prophylactically may be as high as 1 in 2000.

Acute Disease↗
PubMed1985

Wright (a + b-) human erythrocytes and Plasmodium falciparum malaria.

We find Wr(a + b-) erythrocytes of donor M. Fr., which appear to carry a rare glycophorin A variant, to be fully susceptible to invasion by nine isolates of Plasmodium falciparum. Thus we fail to confirm the previous publication on the refractoriness of these erythrocytes. In addition the serum of donor M. Fr., which is known to contain anti-Wrb directed against an epitope located on glycophorin A in close proximity to the erythrocyte membrane, was not found to inhibit P. falciparum invasion of blood group O Rh- red blood cells. Despite this, different lines of evidence still indicate that glycophorin A is one of the receptors for erythrocyte invasion by P. falciparum. The Wrb epitope, however, does not appear to represent a distinct receptor site, which is in contrast to previous suggestions.

ABO Blood-Group System↗
PubMed1984

Receptors on red cells for Plasmodium falciparum and their interaction with merozoites.

The red cell sialoglycoproteins (glycophorins, alpha (A), delta (B) and beta and gamma (C] play a crucial role in the invasion of human red cells by merozoites of Plasmodium falciparum. Red cells deficient in any of the glycophorins, including beta (also known as glycoconnectin), resist infection by this parasite to varying degrees. These cells and other naturally occurring well-characterized glycophorin variants provide extremely powerful tools to dissect the role of these molecules in invasion. The binding of merozoites to human red cells appears analogous to the binding of wheatgerm agglutinin to sialoglycoconjugates. In both systems O- and N-linked oligosaccharides may be involved. Membrane lipid has not been implicated as a receptor for merozoites, but may instead non-specifically modify binding, as may electrostatic and hydrophobic interactions. The results of data using monoclonal antibodies and lectins, although possibly helpful in identifying specific determinants, must be interpreted with caution. Overall the data suggest that the red cell receptors for all strains of P. falciparum tested to date are located on the glycophorins. Accordingly these putative receptors have been used to affinity-purify complementary parasite components which may yet prove to be of protective immunological significance in a vaccine.

Animals↗