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Biomedical subjects

R L Richards

Publications and source records attributed to R L Richards.

13 recordsLinked to original sources
PubMed1979

Choleragen (cholera toxin): a bacterial lectin.

Choleragen (cholera toxin) agglutinated erythrocytes and liposomes containing the toxin receptor, galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosylglucosylceramide (ganglioside GM1). Cells that had been exposed to GM1 were agglutinated, but agglutination was not observed when cells had been exposed to other gangliosides (GM2, GM3, GD1a, GD1b). Choleragen-dependent agglutination of liposomes was slightly less specific, because liposomes containing either GM1 or GD1b, but neither GM2, GD1a, nor GM3 were agglutinated. The oligosaccharide isolated from GM1 inhibited both the agglutination of cells and liposomes containing GM1 and the binding of choleragen to liposomes containing GM1. Galactose and sialic acid were less effective inhibitors of liposomal agglutination and did not inhibit cellular agglutination or binding of choleragen to liposomes. Liposomal agglutination was dependent on choleragen concentration and occurred with the B but not the A protomer of choleragen. These results suggest that choleragen, through its binding to the oligosaccharide portion of a glycolipid, exhibits lectinlike activity, which results in agglutination of liposomes and erythrocytes.

Agglutination↗
PubMed1979

Amyloidosis in Hodgkin's disease: a Scottish survey.

Hodgkin's disease is a rare cause of secondary amyloidosis. In Scotland in the period 1961 to 1974 four patients in whom these 2 conditions were associated have been identified. In one of these the presence of amyloidosis was an unexpected finding at a staging laparotomy for Hodgkin's disease. The clinical and pathological features are summarised. The development of amyloid disease is usually suspected by the finding of proteinuria, which is rarely present in uncomplicated Hodgkin's disease. A distinction is made between a nephrotic syndrome due to glomerulopathy, which is an early complication of Hodgkin's disease and improves with treatment of the primary condition, and the nephrotic syndrome due to amyloidosis which occurs late in the course of the illness and is irreversible and rapidly progressive.

Adult↗
PubMed1979

Interactions of C-reactive protein and complement with liposomes. II. Influence of membrane composition.

We found previoulsy that interaction of C-reactive protein (CRP) with liposomal model membranes resulted in complement(C)-dependent membrane damage. In the present study, we investigated the influence of membrane composition on the interactions of CRP and C with liposomes. Adsorption experiments showed that binding of CRP was greatest to strongly positive liposomes. A lesser, but still substantial, extent of CRP binding also was observed with negative liposomes, but negligible amounts of CRP bound to neutral or weakly positive liposomes. CRP-mediated consumption of hemolytic C, and C-dependent glucose release from liposomes both were strongly influenced by liposomal charge, positive being superior to negative. Glucose release and, to a lesser extent, consumption of hemolytic C were inversely related to phospholipid fatty acyl chain length. Phospholipid fatty acyl unsaturation and liposomal cholesterol concentration both had strong influences on C consumption and glucose release. The data suggest that CRP-mediated C consumption and membrane damage require an optimum membrane fluidity. Complement damage in the presence of CRP was enhanced by certain sphingolipids and also by digalactosyl diglyceride, but not by sphingomyelin. Our results thus demonstrate that CRP-mediated C consumption and C-dependent membrane damage both are influenced by the liposomal membrane composition.

Adsorption↗
PubMed1979

Activation of human complement by liposomes: a model for membrane activation of the alternative pathway.

Liposomal model membranes were found to activate the alternative pathway of human complement. Activation was measured by C3 conversion and component consumption in serum that had been incubated with liposomes. C3 conversion did not require C1 or C2 of the classical pathway, since it was observed in serum from a C1r-deficient patient, serum from a C2-dificient patient, and normal serum in buffer containing EGTA and MgCl2. The incubation of liposomes with C2-deficient serum resulted in consumption of components C3 through C9 with no consumption of C1 or C4 in a profile typical of alternative pathwya activation. The reaction was further shown to require alternative pathway factor D, and to be independent of antibody. Activation of the alterative pathway was dependent on the membrane composition of the liposomes. A positive charge was required for liposomes to produce C3 conversion. Liposomal cholesterol concentration and phospholipid fatty acyl chain length and unsaturation all influenced activation, suggesting the importance of membrane fluidity. Positively charged liposomes containing dimyristoyl phosphatidylcholine and cholesterol required the presence of certain glycolipids for C3 conversion. The activation of the alternative complement pathway by liposomes of defined membrane composition may provide a suitable model for the study of alternative pathway activation by cellular membranes.

Agammaglobulinemia↗
PubMed1977

Effect of the A and B protomers of choleragen on release of trapped glucose from liposomes containing or lacking ganglioside GM1.

Liposomes containing trapped glucose were used to examine the interaction of the A and B protomers of choleragen with ganglioside GM1 and lipid model membranes. The B protomer (choleragenoid) was as effective as choleragen in causing release of trapped glucose from liposomes containing GM1; the A protomer did not release glucose from GM1 liposomes. Neither choleragen nor the A or B protomers caused release of trapped glucose from glycolipid-free liposomes. Anti-choleragen and complement, however, caused release of trapped glucose from ganlioside-free liposomes previously incubated with the A protomer but not from those incubated with the B protomer or choleragen. These results suggest that the A protomer, but not intact choleragen or B protomer, bound to ganglioside-free liposomes. Presumably, the A protomer must be freed of the constraints present in the intact choleragen in order to interact with the liposomal model membrane system.

Bacterial Proteins↗
PubMed1977

Interactions of C-reactive protein and complement with liposomes.

Interactions between C-reactive protein (CRP) and liposomal model membranes containing phosphatidylcholine were investigated. These interactions, in the presence of human serum, resulted in consumption of each of the components of the classical complement pathway (C1-C9) and also resulted in complement-dependent damage and release of trapped glucose from certain types of liposomes. CRP-initiated lysis of liposomes was strongly dependent upon membrane lipid composition. Optimal activity occurred with positively charged liposomes containing galactosylceramide (galactocerebroside); positively charged liposomes lacking galactocerebroside released much less glucose, while negatively charged liposomes, either with or without galactocerebroside, did not release glucose at all. Glucose release was inhibited by free phosphocholine. Lesser, but significant, "background" glucose release independent of the presence of CRP also was observed with positively charged liposomes containing galactocerebroside, and this was associated with marked preferential consumption of the later-acting complement components (C3-C9). C2-deficient human serum failed to support CRP-dependent glucose release, but glucose release was observed upon reconstitution of the serum with C2. Guinea pig complement also did not support CRP-mediated glucose release, but upon addition of human C1q substantial glucose release was observed. We conclude that (i) CRP can sensitize appropriate liposomes for complement-dependent damage via the primary complement pathway starting at the level of C1q; (ii) of those studied, liposomes that are most susceptible to membrane damage contain phosphatidylcholine, have a positive charge, and contain a ceramide glycolipid; and (iii) such liposomes also are sensitive, although to a much lesser degree, to complement-dependent lysis initiated in the absence of CRP and involving consumption of terminal in excess of early acting complement components.

C-Reactive Protein↗
PubMed1977

Cholesterol-dependent human complement activation resulting in damage to liposomal model membranes.

Human (but not guinea pig) complement-mediated damage. It was concluded that human complement was activated spontaneously by liposomes containing a high concentration (71 mol %) of cholesterol. This occurred in the absence of any recognizable antigen or antibody, and did not occur at a low concentration (43 mol %) of cholesterol. Activation of complement resulted in membrane damage and release of trapped liposomal glucose. The complement activity was inhibited by preheating (56 degrees C, 30 min), 10 mM Mg2EDTA3 or EGTA, and by prior adsorption with insoluble immune complexes. Almost all human sera had some reactivity, but it ranged from very low levels (less than 7% liposomal glucose release) to very high levels (greater than 50% glucose release). Complement activation appeared to be mediated by a serum factor which could be removed by adsorption and which was partially heat labile. The factor was transferred by adding heated high reacting human serum to unheated low reacting human serum, or to guinea pig serum. The serum factor, although quantitatively diminished in potency due to heat lability, caused equal activation of each of these two latter complement sources in the presence of high cholesterol liposomes. It did not cause activation of C4-deficient guinea pig complement. These data suggested that the classical complement pathway was activated. The liposomal membrane composition had an influence on this phenomenon. Activities of about half of the human sera were enhanced when galactosyl ceramide, or ceramide alone, was present in the liposomes. Activity was enhanced by longer fatty acyl chain lengths of lecithin when dimyristoyl-, dipalmitoyl-, or distearoyllecithin was employed in the liposomes. Liposomes containing sphingomyelin as the only phospholipid were not sensitive to cholesterol-dependent complement-mediated damage. It was concluded that human complement was activated in the presence of high concentrations of membrane cholesterol and that this was caused by an uncharacterized serum factor and was influenced by the lipid composition of the membrane.

Ceramides↗