Hevein-specific recombinant IgE antibodies from human single-chain antibody phage display libraries

IgE antibodies distinctively recognising allergenic epitopes would be ideal reagents in immunodiagnostics to detect and quantify allergens, as well as for the development of allergy diagnostics and therapeutics. We have isolated recombinant human IgE antibodies specific for the major latex allergen, hevein, from antibody phage display libraries using a green fluorescent protein (GFP)-hevein fusion as a selection antigen. Human IgE phage display libraries were constructed by combining the IgE heavy chain genes to kappa and lambda light-chain genes which were isolated from lymphocytes of a latex allergic patient. The screening of antibody libraries resulted in the enrichment of two hevein-binding scFvs designated as 1A4 and 1C2. Both antibodies showed specific binding to the hevein that could be inhibited by both the recombinant GFP-hevein and native hevein isolated from latex examination gloves. The scFvs were prone to aggregate and, thus, for further characterisation, they were converted to Fab fragments with human IgG1 or IgE isotype. Similar hevein-binding properties of the 1A4 and 1C2 Fab fragments and human IgE serum pool, conventionally used in the detection of latex allergens, demonstrate the potential utility of these recombinant antibodies for the analysis of latex allergen.     

Maternal Vitamin C and Iron Intake during Pregnancy and the Risk of Islet Autoimmunity and Type 1 Diabetes in Children: A Birth Cohort Study

Our aim was to study the associations between maternal vitamin C and iron intake during pregnancy and the offspring’s risk of developing islet autoimmunity and type 1 diabetes. The study was a part of the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) prospective birth cohort including children genetically at risk of type 1 diabetes born between 1997–2004. The diets of 4879 mothers in late pregnancy were assessed with a validated food frequency questionnaire. The outcomes were islet autoimmunity and type 1 diabetes. Cox proportional hazards regression analysis adjusted for energy, family history of diabetes, human leukocyte antigen (HLA) genotype and sex was used for statistical analyses. Total intake of vitamin C or iron from food and supplements was not associated with the risk of islet autoimmunity (vitamin C: HR 0.91: 95% CI (0.80, 1.03), iron: 0.98 (0.87, 1.10)) or type 1 diabetes (vitamin C: 1.01 (0.87, 1.17), iron: 0.92 (0.78, 1.08)), neither was the use of vitamin C or iron supplements associated with the outcomes. In conclusion, no association was found between maternal vitamin C or iron intake during pregnancy and the risk of islet autoimmunity or type 1 diabetes in the offspring.     

European survey on Campylobacter surveillance and diagnosis 2001

Two surveys have been conducted on behalf of the Campylobacter Working Group with the aim of assessing the feasibility of a European network on human Campylobacter infections. The first survey, conducted in 18 countries, collected information about diagnostic methods used for surveillance purpose while the second one, conducted among 10 European countries, gathered data on diagnostic methods and procedures in primary laboratories. Seventeen of the 18 countries had a surveillance system for Campylobacter infections and 13 a national reference laboratory. The case definition used for the surveillance in all these countries included laboratory confirmation. No commonly applicable subtyping methods were applied. Concerning primary laboratories dealing with Campylobacter infections, only a few of them reported directly to the national level, and antimicrobial susceptibility testing was performed by about half of the laboratories. These surveys indicated that a basic infrastructure for a wide European Campylobacter surveillance exists.     

Laxative treatment elevates plasma homocysteine: a study on a population-based Swedish sample of old people

Objectives Elevated plasma homocysteine might indicate an increased risk of cancer, and cardiovascular and neurological diseases. The homocysteine level depends on the supply of folate and cobalamine, and constipation and/or laxative treatment might compromise this supply. The present study examined the impact of constipation and laxative treatment on the blood levels of homocysteine, folate and cobalamine in a population-based sample of aged people, including consideration of frailty and impaired renal function, both of which may also influence the homocysteine level.Methods The study was based on biochemical tests in 341 females and 183 males aged 82 years or older. The concentrations of homocysteine (plasma), folate, cobalamine and urea (serum) were measured in subjects with and without ongoing treatment with laxative drugs. Values were adjusted for age, gender and frailty, as well as for clinical diagnoses and drug therapies known to affect homocysteine levels.Results Homocysteine levels were increased and those of folate reduced in aged subjects on laxatives. Homocysteine remained elevated after adjusting for frailty and various neurological disorders. There was no significant effect on homocysteine and folate in constipated subjects without laxatives.     

Does aspirin protect against Alzheimer's dementia? A study in a Swedish population-based sample aged > or =80 years

Objective It has been reported that aspirin and other non-steroidal anti-inflammatory drugs (NSAID) may protect against dementia of Alzheimer's type and/or vascular dementia. However, co-morbidity and the dose of aspirin may be critical. A major indication for low-dose aspirin is prophylaxis after stroke and transient ischaemic attacks, conditions that may obscure an anti-dementia effect by the drug. Alternatively, low-dose aspirin may be insufficient if the protective effect is due to an anti-inflammatory mechanism. The aim of this study was to assess whether high-dose or low-dose aspirin may protect against Alzheimer's dementia in subjects aged 80 years. For comparison, effects of (other) NSAID, paracetamol and d-propoxyphene were studied.Methods Global, cross-sectional, and longitudinal (1991–2000) epidemiological analyses of clinical, cognitive and drug treatment data on 702 individuals 80 years old or more (351 twin pairs of same sex), all alive at inclusion: mean age 83.9 years (80–99 years). Calculations were made with logistic regression of associations between use of various analgesics and cognitive function, after adjustment for age, gender, and cardiovascular and cerebrovascular diseases.Results Users of high-dose aspirin had significantly lower prevalence of Alzheimer's dementia and better-maintained cognitive function than non-users. There were numerically similar but not significant associations with use of low-dose aspirin and other NSAID. There were no such associations with use of either paracetamol or d-propoxyphene.Conclusion Aspirin might protect against Alzheimer's disease, but controlled trials are warranted.     

An outbreak of viral gastroenteritis in a mother-and-child health clinic

An outbreak of diarrhoeal disease in a modern mother-and-child health clinic prompted the health authorities to initiate a retrospective cohort study in order to assess the scope of the outbreak and to identify possible risk factors. The management of the clinic had been rather concerned because four similar outbreaks had occurred during the last two years. A total of 151 guests, i.e. mothers with their children, who had arrived some days before the peak of the outbreak for a three-week-stay and another 15 guests who had arrived earlier and had extended their stay were enrolled in the study which mainly focused on the possible role of treatment measures as risk factors. In addition, a total of 49 staff members were requested to provide information about symptoms, working area and attendance at work. Relevant data were available from 164 of 166 guests and 47 of 49 staff members (response rates 98.8% and 96.0%, respectively). The attack rate among guests was 44.0% (adults 27.0%, children 54.0%) and among staff 23.4%. The mean age of affected children (3.5 years) was significantly lower than that of those not affected (6.3 years). The main symptoms were diarrhoea and vomiting. The sudden start of the outbreak suggested a single source of infection which, however, remained unknown. Person-to-person transmission was supposed to be the cause of the following spread. No association between distinct treatment measures and the disease was proven by the cohort study. Norwalk-like viruses as well as astroviruses were detected by polymerase chain reaction in specimens taken from seven patients. No other enteropathogenic agents were found. Regarding the special conditions in a mother-and-child health clinic where social contacts among guests are much more frequent and intensive than among patients in a "normal" hospital, measures to prevent the spread of gastrointestinal infections should concentrate on early recognition and isolation of symptomatic individuals. Guests and staff members should be instructed to keep to the rules of personal hygiene, especially handwashing. If disinfection is required, it should be virucidal.     

High-calcium intake abolishes hyperoxaluria and reduces urinary crystallization during a 20-fold normal oxalate load in humans

Background: The aim of the study was to test whether increasing dietary calcium intake lowers intestinal oxalate absorption and thereby prevents hyperoxaluria and urinary crystallization during a 20-fold normal oxalate load in healthy subjects. Methods: Fourteen healthy male volunteers (age 23-44 years, BMI 21.5-27.7 kg/m²) collected 24-h urines while on free choice diet as well as on two standardized diets. The latter contained 2545 kcal, 2500 ml of mineral water, 102 g of protein, 13.6 g of sodium chloride and 2220 mg of oxalate ( 20-fold content of an average diet). Subjects were studied twice while on the standardized diet, once while eating a normal amount of calcium (1211 mg/day, oxalate-rich, diet), and once while eating 3858 mg of calcium /day (calcium and oxalate-rich diet). Results: Compared with the free-choice diet (322±36 &mgr;mol/d), UOx X V increased to 780±722 &mgr;mol/d on the oxalate-rich diet (P=0.001) and fell again to 326±31 &mgr;mol/d on calcium and oxalate-rich diet (P=0.001 vs oxalate-rich diet). Urinary glycolate (a metabolic precursor of Ox) always remained below the upper limit of the normal range and did not change between different diets, indicating that changes in UOx x V reflect respective variations in intestinal absorption of Ox. UCa x V was 4.60±0.45 mmol/d on the free choice diet and 3.20±0.32 mmol/d on the oxalate-rich diet (P=0.011 vs free-choice diet); it increased to 7.28±0.74 mmol/d on the calcium- and oxalate-rich diet (P=0.001 vs free-choice and oxalate-rich diets). As indicated by the AP (CaOx) index (Tiselius), urinary supersaturation did not vary significantly between the three diets. In freshly voided morning urines (studied in 8/14 subjects) on the oxalate-rich diet, CaOx crystals or crystal aggregates of up to 80 &mgr;m diameter were found in 5/8 urines, whereas this never occurred on the free-choice diet and only once on the calcium- and oxalate-rich diet. Conclusion: Increasing calcium intake while eating Ox-rich food prevents dietary hyperoxaluria and reduces CaOx crystallization in healthy subjects. This further illustrates that dietary counseling to idiopathic calcium-stone formers should ensure sufficient calcium intake, especially during oxalate-rich meals.