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PubMed1985

Paroxysmal nocturnal haemoglobinuria.

The analysis of the abnormality of the membrane in paroxysmal nocturnal haemoglobinuria is an exercise in complexity complexified--of Ossa atop Pelion. To understand it, we will need to understand fully the complexities of the complement system and the complexities of the structure of the membrane and the complexity of their concert interaction. Added to this are the complexities of growth and development of the haematopoietic cells--a problem we have not discussed at all despite its importance in the pathophysiology of PNH. It is little wonder that a disease which is uncommon but not rare continues to fascinate investigators from a wide variety of disciplines. If, as has been (falsely) said, more people studied the disease than had it, it would be because it presents questions of such fundamental interest. In unravelling its mysteries, many problems related to the normal functioning of cells, complement and a haematopoiesis have been and will continue to be solved.

Acetylcholinesterase↗
PubMed1985

Growth cycle-dependent generation of complement-resistant Leishmania promastigotes.

The ability of in vitro grown Leishmania promastigotes to resist lysis by complement and survive in undiluted human serum was related to the species of Leishmania and the growth phase in culture. Promastigotes from log phase cultures were always killed in undiluted serum, whereas survival of stationary phase promastigotes varied among species. All L. major and L. m. amazonensis were killed, while up to 30% of L.b. panamensis and 10% of L. donovani survived. Lysis of promastigotes by human serum was inhibited in heat-inactivated serum and EDTA-chelated serum, indicating that activation of complement was responsible for killing. Therefore, during growth in vitro, some strains of Leishmania promastigotes can undergo development from a complement-susceptible to -resistant stage. Stationary phase promastigotes of L.b. panamensis which survived in undiluted human serum were capable of subsequent growth in culture, and were also able to initiate infection in Mystromys albicaudatus. Organisms selected on the basis of complement resistance were more infective for M. albicaudatus than either log phase promastigotes or unselected promastigotes from stationary cultures. These data support the notion that the life cycle of Leishmania includes an infective stage promastigote which is generated during growth within the sandfly and which, on inoculation, is able to survive the potentially lethal effect of normal serum before uptake by host macrophages.

Adult↗
PubMed1979

Multiple effects of a diamidine (propamidine) on complement activation.

Propamidine, one of the diamidines used against infections with babesiae has inhibitory and enhancing effects on complement activation as assessed by immune haemolysis of sensitized sheep red cells. Utilization of C1 is powerfully, that of C3 weakly improved by propamidine while activation and/or fixation of C4, C5 and to a lesser degree of C8 and C9 are inhibited. At low concentrations of propamidine (less than 2 mM) the enhancing effects, at higher concentrations the inhibitory effects predominate. Inhibition is produced, in some cases certainly, in others likely, by interference of propamidine with binding properties of complement components. None of the complement enzymes, C1s, C42 or C3bBb was inhibited in its hydrolytic activity. The possible significance of propamidine actions is discussed.

Amidines↗
PubMed1979

[Complement system].

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Complement Activation↗
PubMed1979

Immune complexes and complement in rheumatoid arthritis.

Immune complexes have been shown to occur frequently during rheumatoid arthritis. They have been found in blood, in the synovium and in other extravascular lesions. The recent development of methods for the quantitation of immune complexes provided new tools to evaluate the possible role of immune complexes in rheumatoid arthritis. Immune complexes which appear in synovial fluid are in higher concentration than in serum and have particular physicochemical properties. They likely result from a local formation in the synovium and seem to be directly involved in the generation of the local inflammation. High levels of circulating immune complexes are usually associated with the development of extra-articular vascular lesions. One of the major biological activity of immune complexes is to activate the complement system. There is indeed evidence of complement activation in circulating blood as well as in synovial fluid in patients with rheumatoid arthritis. The presence and the concentration of complement breakdown products in these fluids correlates with the clinical activity. Therefore, the analysis of immune complexes and of complement components appears useful for diagnosis and follow-up, and for the understanding of the pathogenesis of the disease.

Antigen-Antibody Complex↗