High Affinity Antibodies to Plasmodium falciparum Merozoite Antigens Are Associated with Protection from Malaria

Malaria kills almost 1 million people every year, but the mechanisms behind protective immunity against the disease are still largely unknown. In this study, surface plasmon resonance technology was used to evaluate the affinity (measured as k(d)) of naturally acquired antibodies to the Plasmodium falciparum antigens MSP2 and AMA1. Antibodies in serum samples from residents in endemic areas bound with higher affinities to AMA1 than to MSP2, and with higher affinities to the 3D7 allele of MSP2-3D7 than to the FC27 allele. The affinities against AMA1 and MSP2-3D7 increased with age, and were usually within similar range as the affinities for the monoclonal antibodies also examined in this study. The finding of MSP2-3D7 type parasites in the blood was associated with a tendency for higher affinity antibodies to both forms of MSP2 and AMA1, but this was significant only when analyzing antibodies against MSP2-FC27, and individuals infected with both allelic forms of MSP2 at the same time showed the highest affinities. Individuals with the highest antibody affinities for MSP2-3D7 at baseline had a prolonged time to clinical malaria during 40 weeks of follow-up, and among individuals who were parasite positive at baseline higher antibody affinities to all antigens were seen in the individuals that did not experience febrile malaria during follow up. This study contributes important information for understanding how immunity against malaria arises. The findings suggest that antibody affinity plays an important role in protection against disease, and differs between antigens. In light of this information, antibody affinity measurements would be a key assessment in future evaluation of malaria vaccine formulations

Neutrophil mobility during anaesthesia in children. A trial of ascorbate premedication

In 20 healthy children undergoing elective surgery, mobility of neutrophils, both unstimulated and stimulated by endotoxin, was studied using a millipore filter system with microscopic determination of leading front migration. Paired samples were incubated with 10(-2) mol l-1 calcium ascorbate and ten children also received 10 mg kg-1 ascorbic acid before premedication. Stimulation of mobility was reduced after the opioid premedication (P less than 0.05) in the ascorbate group only, but not significantly during anaesthesia and surgery. A few individuals showed persisting abnormally low values. No effect of ascorbate in vivo or in vitro was demonstrated. There were no infections

Prospective study of cancer in patients with hypogammaglobulinaemia.

Among 377 patients with primary hypogammaglobulinaemia, mainly common variable immunodeficiency (CVID), 316 patients survived the first 2 years after diagnosis and were the subject of a study of cancer incidence. Among the 220 patients with CVID, there was a 5-fold increase of cancer due mainly to large excesses of stomach cancer (47-fold) and lymphomas (30-fold). The excess of stomach cancer is probably related to the high frequency of achlorhydria in CVID. 3 of the 7 patients with stomach cancer and CVID survived for 5 years or longer

Official Criminal Careers

Official criminal records are one of the most well-known sources of crime data. Accordingly, this chapter reviews the process whereby the criminal record searches were conducted in order to construct the life-course conviction records among the Cambridge Study in Delinquent Development males from ages 10 to 56. This rich offending information is then analyzed with a particular focus on the key criminal career dimensions of onset age, offending continuity, and criminal career length. The incarceration histories of the Cambridge Study in Delinquent Development males are briefly reviewed also

Mannose-binding lectin 2 (MBL2) gene polymorphism in asthma and atopy among adults

Mannose-binding lectin (MBL) insufficiency due to polymorphisms in the MBL2 gene causes an opsonization defect, which has been connected to infections and atopy. We investigated the significance of MBL2 genotypes with regard to persistent asthma and atopy among adults. The genotypes were determined in 243 adults with persistent asthma and 400 controls. Atopy was determined by skin-prick test. As a result, the carriage of −221 base pairs (bp) promoter region variant allele X (nucleotide change G→C; alleles Y→X, respectively) causing low MBL expression proved to be a significant risk factor for asthma in non-atopic males [odds ratio (OR) = 2·52, 95% confidence interval (CI) = 1·23–5·15; P = 0·01]. Furthermore, the X-allele carriage was associated with the decrease in lung function (forced expiratory volume at 1 s, FEV(1)) during follow-up in the patients with asthma (P= 0·033), the effect being strongest for non-atopic asthmatics (P= 0·042). The MBL2 genotype had no clear effect on the occurrence of atopy in adults. In conclusion, our results abrogate the previously suggested predisposing effect of MBL insufficiency on atopy at least in adults. However, as MBL is a complement component participating in immune defence against microbes, and as in the pathogenesis of non-atopic asthma infectious agents are probably involved, the gene–environment interactions between MBL and infections should be assessed further with regard to asthma