Temporal variations in immune responses to conserved regions of Plasmodium falciparum merozoite surface proteins related to the severity of a prior malaria episode in Gabonese children

We measured cellular and humoral responses to conserved regions of Plasmodium falciparum merozoite surface proteins 1 and 2 (MSP-1 and MSP-2) at different times during and after acute infection in matched groups of Gabonese children who presented with either mild or severe malaria. We used an MSP-1(19) recombinant protein and peptides corresponding to conserved epitopes in MSP-1 and MSP-2 N- and C-terminal regions. The prevalences of peptide-induced cell-mediated responses were maximal in both groups when they were healthy, but were consistently higher in the mild malaria group, whereas peptide-specific antibody responses were consistently highest in the severe malaria group. Recombinant MSP-1(19) protein-specific antibody levels in the 2 groups were similar both prior to and 1 month post-treatment but declined later when the children were healthy and parasite-free, to a significantly lower level in those admitted with severe malaria, reflecting the profile of the predominant MSP-1(19)-specific immunoglobulin G1 isotype. This finding implies a defect in the ability of children with a history of severe malaria to maintain an antibody response putatively associated with immunity to P. falciparum malaria.     

Antigens in pigeon breeder's disease: the use of pigeon dropping antigens in detecting antibody activity.

Sera from patients with pigeon breeder's disease were analysed for precipitating antibodies by immunodiffusion and immunoelectrophoresis using whole pigeon dropping extract (PDE) and a purified fraction of PDE (PDE1) as antigens. For comparison, sera from asymptomatic pigeon breeders and normal individuals were also tested for precipitating antibodies. Whereas whole PDE formed precipitin lines with normal serum as well as with serum from symptomatic and asymptomatic pigeon breeders, PDE1 formed precipitin lines only with serum from individuals exposed to pigeons, This suggests that whole PDE forms non-specific (non-antigen-antibody reactions) as well as specific precipitin lines, while PDE1 appears to form only specific lines. These data indicate that whole PDE has limited usefulness in studies of pigeon breeder's disease. It is also possible that PDE1 will be useful in studies of this disease.     

The incidence and relationship of the lateral ramus prominence to the mandibular foramen.

A study was undertaken to determine the incidence of the lateral ramus prominence and its relationship to the mandibular foramen. The lateral ramus prominence, as determined by inspection and palpation, was identified on both the right and left rami of all specimens. Bilateral measurements were made on fifty randomly selected adult dentulous mandibles. Significant correlation coefficients were obtained for all measurements between right and left rami. Therefore, either the left or right side measurement for each parameter was selected at random, and the data were subjected to statistical analysis. The lateral ramus prominence varied from 4.7 mm. anterior to 4.7 mm. posterior to the foramen, and from 0.9 mm. to 16.2 mm. superior to the foramen. It was located anterior to the foramen 66 per cent of the time.     

Cardiac troponin I mutations in Australian families with hypertrophic cardiomyopathy: clinical, genetic and functional consequences

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder caused by mutations in sarcomeric proteins. Cardiac troponin I (cTnI) is a key switch molecule in the sarcomere. Mutations in cTnI have been identified in <1% of genotyped HCM families. METHODS: To study the prevalence, clinical significance and functional consequences of cTnI mutations, genetic testing was performed in 120 consecutive Australian families with HCM referred to a tertiary referral centre, and results correlated with clinical phenotype. Each cTnI mutation identified was tested in a mammalian two-hybrid system to evaluate the functional effects of these mutations on troponin complex interactions. RESULTS: Disease-causing missense mutations were identified in four families (3.3%). Two mutations were located at the same codon in exon 7 (R162G, R162P), and two in exon 8 (L198P, R204H). All four mutations change amino acid residues which are highly conserved and were not found in normal populations. Follow-up family screening has identified a total of seven clinically affected members in these four families, with a further four members who carry the gene mutation but have no clinical evidence of disease. Age at clinical presentation was variable (range 15-68 years) and the mean septal wall thickness was 19.3 +/- 4.6 mm (range 7-33 mm) in clinically affected individuals, including children. In all four families, at least one member had a sudden cardiac death event, including previous cardiac arrest, indicating a more malignant form of HCM. All four mutations disrupted functional interactions with troponin C and T and this may account for the increased severity of disease in these families. CONCLUSIONS: Gene mutations in cTnI occur in Australian families with HCM with a prevalence higher than previously reported and may be associated with a clinically more malignant course, reflecting significant disruptions to troponin complex interactions.     

Evidence for the presence of Mn(III) intermediates in the bacterial oxidation of Mn(II)

Bacterial oxidation of Mn(II) to Mn(IV) is believed to drive the oxidative segment of the global biogeochemical Mn cycle and regulates the concentration of dissolved Mn(II) in the oceanic water column, where it is a critical nutrient for planktonic primary productivity. Mn(II) oxidizing activity is expressed by numerous phylogenetically diverse bacteria and fungi, suggesting that it plays a fundamental and ubiquitous role in the environment. This important redox system is believed to be driven by an enzyme or enzyme complex involving a multicopper oxidase, although the biochemical mechanism has never been conclusively demonstrated. Here, we show that Mn(II) oxidation by spores of the marine Bacillus sp. strain SG-1 is a result of two sequential one-step electron transfer processes, both requiring the putative multicopper oxidase, MnxG, in which Mn(III) is a transient intermediate. A kinetic model of the oxidation pathway is presented, which shows that the Mn(II) to Mn(III) step is the rate-limiting step. Thus, oxidation of Mn(II) appears to involve a unique multicopper oxidase system capable of the overall two-electron oxidation of its substrate. This enzyme system may serve as a source for environmental Mn(III), a strong oxidant and competitor for siderophore-bound Fe(III) in nutrient-limited environments. That metabolically dormant spores catalyze an important biogeochemical process intimately linked to the C, N, Fe, and S cycles requires us to rethink the role of spores in the environment.