Glycoproteins of trypanosomes: their biosynthesis and biological significance

1. Trypanosomes are unicellular parasites that cause human sleeping sickness in Africa and Chagas' disease in South America. Glycoproteins are important components of their plasma membrane. 2. The bloodstream form of the extracellular salivarian African trypanosome (e.g. Trypanosoma brucei) has the ability to express on its cell surface a repertoire of variant surface glycoproteins (VSGs) and in so doing, evades the immune response of the host (antigenic variation). 3. The VSG is probably synthesized initially in a manner like that of the membrane-bound glycoproteins of mammalian systems, but it also undergoes some novel post-translational modifications. 4. The stercorarian South American trypanosome (Trypanosoma cruzi) is an intracellular parasite which expresses different glycoproteins on its plasma membrane at various stages of its life-cycle, but does not exhibit antigenic variation. 5. The biosynthesis and functions of trypanosomal glycoproteins are compared with those of mammalian glycoproteins, and are discussed with particular reference to potential targets for chemotherapy and immunotherapy of trypanosomiasis.     

DNA polymorphism of human HLA-linked complement C4 allotypes, including C4 null alleles, in the Finnish population

Human HLA-linked complement C4 gene products, C4A and C4B, show extensive genetic polymorphism. In both loci, an allele without a gene product, C4 null, is also observed. We have performed a restriction enzyme analysis of genomic DNA samples from individuals having all common (frequency over 1%) C4 protein allotypes observed in the Finnish population. Only one allotype-specific RFLP marker was observed. With some enzymes a DNA polymorphism was observed, which was not detectable by C4 protein typing. Analysis of 10 different C4B null haplotypes and 4 C4A null haplotypes suggested that only one haplotype, HLA-B8 C4A0 B1, carried a C4A gene deletion. This was observed in all 4 unrelated individuals homozygous for this haplotype.     

Amino acid sequence homology between the enzymic domains of diphtheria toxin and Pseudomonas aeruginosa exotoxin A

Despite similarities in their enzymic properties, diphtheria toxin (DT) and exotoxin A (ETA) of Pseudomonas aeruginosa have major differences in structure and action: consequently, the question of possible evolutionary relatedness of these two proteins remains unanswered. Here we report the existence of significant amino acid sequence homology between the enzymic domain of DT and that of ETA. Major segments of sequence may be aligned with high percentages of identity and of conservative substitutions. The homologous stretches in ETA form much of the active-site cleft in the X-ray crystallographic structure. This evidence implies that these domains, at least, have diverged from a common ancestral protein and that active-site residues have been strongly conserved.     

Thin-film antimony-antimony-oxide enzyme electrode for penicillin determination

A potentiometric penicillinase electrode is reported in which the base pH transducer is a thin-film anti-mony-antimony-oxide electrode deposited by vacuum evaporation. Several enzyme immobilization procedures have been examined and a crosslinked protein film found to be the most appropriate to this type of sensor. The use of an adjacent antimony-antimony-oxide track as a pseudoreference electrode was successfully demonstrated. The overall response was shown to be independent of the stirring rate above 100 rpm, but the kinetics of the response were found to depend markedly on the stirring rate. The intrinsic linear response range was 3 x 10(-4)Mto 7 x 10(-3)M penicillin G. Linearizing transforms that extend the useful range were examined.     

Cholesteryl hemisuccinate alters membrane fluidity, angiotensin receptors, and responses in adrenal glomerulosa cells

We examined the effects of cholesteryl hemisuccinate on membrane fluidity and angiotensin II (AII) actions in bovine adrenal glomerulosa cells. Incubating cells with cholesteryl hemisuccinate decreased membrane fluidity and markedly inhibited AII binding. The effect on binding was characterized by a decrease in AII receptor number. The effects of AII on phosphatidyl inositol turnover and calcium fluxes, proposed intermediaries of AII actions on aldosterone secretion, were less impaired than AII binding by cholesteryl hemisccinate. AII stimulation of aldosterone secretion was preserved despite the decrease in AII binding after cholesteryl hemisuccinate treatment. These results indicate that AII binding can be dissociated from its effects on aldosteronogenesis by a reagent that alters membrane fluidity.     

Clotting Problems with the Teflon-Silastic Arteriovenous Shunt in Patients on Regular Haemodialysis

Episodes of clotting that occurred in 22 patients on regular haemodialysis were studied over a six-month period. The venous pressure during dialysis and the radiology of the Teflon-Silastic arteriovenous shunt were found to be satisfactory guides for the management of the shunt. The failure of the shunt during the early stage was mainly due to technical reasons. Histological study of the excised vessels in removed long-term shunts showed that these had failed because of rigidity and thickening of the vessel wall due to calcium and iron deposits or chronic inflammation, or both.