HMGCR is a genetic modifier for risk, age of onset and MCI conversion to Alzheimer's disease in a three cohorts study.

Several retrospective epidemiological studies report that utilization of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibitors called statins at mid-life can reduce the risk of developing sporadic Alzheimer's disease (AD) by as much as 70%. Conversely, the administration of these inhibitors in clinically diagnosed subjects with AD confers little or no benefits over time. Here, we investigated the association between AD and HMGCR rs3846662, a polymorphism known to be involved in the regulation of HMGCR exon 13 skipping, in a founder population and in two distinct mixed North American populations of converting mild cognitively impaired (MCI) subjects (Alzheimer's disease Cooperative study (ADCS) and Alzheimer's disease Neuroimaging Initiative (ADNI) cohorts). Targeting more specifically women, the G allele negative (G-) AD subjects exhibit delayed age of onset of AD (P=0.017) and significantly reduced risk of AD (OR: 0.521; P=0.0028), matching the effect size reported by the apolipoprotein E type 2 variant. Stratification for APOE4 in a large sample of MCI patients from the ADCS cohort revealed a significant protective effect of G negative carriers on AD conversion 3 years after MCI diagnosis (odds ratio (OR): 0.554; P=0.041). Conversion rate among APOE4 carriers with the HMGCR's G negative allele was markedly reduced (from 76% to 27%) to levels similar to APOE4 non-carriers (27.14%), which strongly indicate protection. Conversion data from the independent ADNI cohort also showed significantly reduced MCI or AD conversion among APOE4 carriers with the protective A allele (P=0.005). In conclusion, HMGCR rs3846662 acts as a potent genetic modifier for AD risk, age of onset and conversion.

Specific IgG levels to wheat in wheat tolerant professional cyclists may depend on a homeostatic immune response to a high consumption of wheat.

BACKGROUND: Implication of IgG antibodies to wheat has been alleged in gastrointestinal symptoms. Precise data on the specific IgG levels in healthy subjects are lacking. Our objectives are to compare levels of IgG antibodies to wheat protein fractions in healthy non atopic or atopic subjects, and in healthy professional cyclist subjects, taking into account the quantitative consumption of wheat. METHODS: 24 control subjects and 26 professional cyclist subjects were selected. ELISA was performed to 2 wheat commercial solutions and to 3 wheat protein fractions. RESULTS: No significant difference was observed between non atopic and atopic subjects. For wheat flour extract, physiological norm determined was 3.27 mg/L sIgG concentration +/- 1.25 CI (95% confidence intervals) for the professional cyclists (vs 1.56 mg/L +/- 0.91 CI in control subjects, p-value: 0.040). For gluten solution, physiological norm was 1.42 mg/L +/- 0.60 CI (vs 0.50 +/- 0.24 CI in control subjects, p-value: 0.010). CONCLUSION: Atopic and non atopic healthy adults have a similar level of sIgG to wheat. Increased levels of sIgG are observed correlatively with an excessive consumption, and could contribute to homeostasis of tolerance. Studies searching for a pathogenic role of sIgG in certain pathologies should take into account the quantitative consumption.

Poster - Thur Eve - 52: Clinical use of nanoDots: In-vivo dosimetry and treatment validation for stereotactic targets with VMAT techniques.

A newly acquired nanoDot In-Light system was compared with TLD-100 dosimeters to confirm the treatment dose in the multiple cases: an electron eye treatment, H&N IMRT and VMAT validation for small targets. Eye tumour treatment with 9 MeV electrons A dose of 1.8 Gy per fraction was prescribed to the 85% isodose. The average dose measured by three TLDs and three Dots was 1.90 and 1.97 Gy. Both detectors overestimated dose, by 2.9% and 6.7% respectively. H&N IMRT treatment of skin cancer with 6 MV photons Dose per fraction is 2.5 Gy. The average doses measured by two TLDs and two Dots were 2.48 and 2.56 Gy, which represent errors of -0.8% and 2.2%, respectively. VMAT validation for small targets using an Agarose phantom, dose 15 Gy A single-tumour brain treatment was delivered using two coplanar arcs to an Agarise phantom containing a large plastic insert holding 3 nanoDots and 4 TLDs. The difference between the average Pinnacle dose and the average dose of the corresponding detectors was -0.6% for Dots and -1.7% for TLDs. A two-tumour brain treatment was delivered using three non-coplanar arcs. Small and large plastic inserts separated by 5 cm were used to validate the dose. The difference between the average Pinnacle dose and the average dose of the corresponding detectors was the following; small phantom 0.7% for Dots and 0.3% for TLDs, large phantom-1.9% for Dots and -0.6% for TLDs. In conclusion, nanoDot detectors are suitable for in-vivo dosimetry with photon and electron beams.

The prevalence of sensitization to lupin flour in France and Belgium: a prospective study in 5,366 patients, by the Allergy Vigilance Network.

OBJECTIVES: To determine the prevalence of sensitization to lupin flour in patients consulting allergists, in order to evaluate the risk of primary and secondary allergies to lupin. METHODS: A prospective study carried out by members of the Allergy Vigilance Network, using prick-tests with a commercial lupin flour extract in patients with various allergic symptoms. The study design classified patients into four groups: peanut allergy, current atopic disease, latent atopy, no atopy. Data were collected and analysed by Network coordinators. RESULTS: Over a two-month period, 88 French and Belgian allergists tested 5,366 patients: 2,680 children and 2,686 adults aged over 16 years. Of the 2,680 children, 11.15% presented with peanut allergy. The frequency of cross-reactivity with lupin was 17.1% for patients with peanut allergy, 2.5% for children with current atopic disease and 1.7% for healthy children with latent atopy. In the 2,686 adults, peanut allergy was diagnosed in 1.86% of patients with cross-reactivity to lupin in 14.6%. Sensitization to lupin was detected in 3.7% of patients with current atopic disease and in 1.8% of those with latent atopy. CONCLUSION: The relative frequency of latent sensitisation to lupin in patients of all ages presenting with atopic disease is a new factor indicating the likelihood of an increase in primary food allergies to lupin flour. This justifies the recent decision requiring mandatory labelling of lupin, and shows the need to inform consumers who may be unaware that this ingredient is being used increasingly. Sensitization to lupin should be searched by prick-tests in any case of peanut allergy. Prick-test to lupin may be valuable whenever a food allergy is suspected when no current food allergens have been identified.

Plant lipid transfer proteins (LTPS): biochemical aspect in panallergen--structural and functional features, and allergenicity.

Lipid transfer proteins (LTPs) are highly conserved and widely distributed throughout the plant kingdom. Several members of LTP family have been identified as relevant allergens in food and pollens. Because of their high resistance to heat treatments and enzymatic digestion, these proteins are allergenic candidates for oral route sensitisation. This review presents biochemical features, allergenicities and cross reactivities of fruit, cereal and pollen LTPs.

Wheat flour allergy: an entire diagnostic tool for complex allergy.

Wheat proteins are involved in respiratory allergy, contact allergy and food allergy. Wheat allergens involve in these pathologies are well-known. However, establishment of wheat allergy diagnostic can be sometimes difficult on account of the complex allergenic composition of skin prick test (SPT) solutions of wheat flour. Therefore, we have studied specific IgE reactivity from patient sera with wheat food allergy, and characterized allergenic composition of wheat SPT solutions by specific antibodies directed to wheat allergens. The results showed that 20 of the 25 sera analyzed contained specific IgE to at least one wheat protein fraction. Among positive sera, 75% have specific IgE to water/salt soluble fraction, 85% to native gluten fractions and 65% to wheat isolate fraction. The results showed also that SPT solutions of wheat flour contained major food allergens from each allergenic fraction. These results highlighted the importance of using fractions, which constitute the whole wheat allergenic pattern, during specific IgE reactivity analyses. Moreover, we have observed that wheat isolate extract (results of food industrial process) contained not only modified allergens (neo-allergens) involve of specific food allergy to wheat isolate but also some native allergens involve in wheat food allergy. Thus, these results showed the importance to use, for wheat in vivo diagnosis together wheat SPT solutions (gluten extract and wheat isolate) in order to differentiate wheat food allergy to specific wheat isolate allergy.

Identification of oleosins as major allergens in sesame seed allergic patients.

BACKGROUND: The prevalence of sesame allergy is increasing in European countries. Cases of severe allergy lack any evidence of specific immunoglobulin (Ig)Es by prick tests and CAPSystem-FEIA. The reasons for this negativity are unknown. METHODS: In 32 patients displaying immediate symptoms such as anaphylactic shock, asthma, urticaria, angioedema, sesame allergy was diagnosed by double-blind placebo-controlled food challenge (DBPCFC) or convincing clinical history. However, 10 patients had negative prick tests and CapSystem-FEIA. The specificity of IgEs was further investigated by enzyme-linked immunosorbent assay (ELISA), isoelectrofocalisation (IEF)-blotting, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) blotting using total sesame extracts and purified fraction of oil bodies. Monospecific rabbit antibodies directed to two oleosin isoforms (15 and 17 kDa) were used. RESULTS: By ELISA, white sesame seed extract allowed the detection of higher levels of IgE than brown sesame extract. In all sera, numerous bands binding IgEs were detected by IEF or SDS-PAGE. In reducing conditions, two bands (15-17 kDa), could be separated from 2S albumin. Oleosins, present in oil bodies fractions, were recognized by IgEs from all sera. CONCLUSION: Oleosins are major allergens of sesame seeds and may be relevant to severe anaphylaxis. Falsely negative prick tests could be due to the lack of oleosins in presently available extracts, or to the fact that epitopes might be buried in the inner molecule. Detection tests currently used to identify sesame allergens based on sesame vicillins or other storage proteins could be insufficient for the detection of sesame seed contamination. Oleosins have been named Ses i 4 (17 kDa) and Ses i 5 (15 kDa), in accordance with the IUIS Nomenclature Committee.

[Allergenicity of lupin flour]. / Allergénicité de la farine de lupin.

Lupin flour is used in human food for its high quality nutritional and functional qualities. The frequency of crossed allergy between lupin flour and peanuts, both members of the family of Leguminosae, is strong, since 68% of patients who are allergic to peanut have shown positive reactions to lupin flour when tested by TPO-DA. Cases of isolated allergy to lupin flour without pre-existence of peanut allergy as well as workplace asthma by inhalation are also rarely seen. The specific allergens of lupin and those that participate in crosses with peanut have been studied by SDS-PAGE and immunoblot. The diversity of allergens contained in different lupin flour has also been studied. Further, the detection of lupin flour in a "pizza" flour which induced a strong allergic reaction exposed its eventual implication as a masked allergen.

[Allergy to cypress pollen: preparation of a reference and standardization extract in vivo]. / Allergie au pollen de cypres: preparation d'un extrait de référence et standardisation in vivo.

Development of Cypress allergy frequency led to the standardization of commercial cypress extract used for diagnosis and immunotherapy. Previous in vitro studies on two cypress pollen species (Cupressus sempervirens and Cupressus arizonica) allowed us to produce an allergenic solution composed by a mixture of both extracts for in vivo standardization. Dilutions of this allergenic solution were tested by prick-test on 44 patients with clinical allergy to cypress pollen to define the dilution that corresponds to a 6 mm wheal conformed to the definition of 100 IR. The mixture of the two major species found in France is justified by the in vitro study results. Extracts revealed complementary allergenic composition: Cup sempervirens showed a wider diversity of allergens whereas Cup arizonica showed a higher content of the major 43 kDa allergen. Thus, according to in vivo analysis, we are able to produce a standardized extract of Cypress pollen expressed in IR.

[Factors playing a role in the increase of localized perfusion observed by single-photon emission-computed tomography during an epileptic seizure]. / Recherche des facteurs impliqués dans l'augmentation de la perfusion localisée observée en tomographie par émission monophotonique au cours d'une crise épileptique.

Ictal SPECT is a valuable method for the presurgical exploration of partial epilepsy. (99m)Tc Ethyl Cysteinate Dimer stable during 6h has contributed to develop ictal studies to evaluate the location of partial seizure. The aim of this study was to investigate some factors playing a possible role on the regional increase of cerebral blood flow (rCBF) Twenty-three patients with refractory partial epilepsy (temporal epilepsy n=16, extratemporal epilepsy n=7) were included. All the patients underwent a presurgical evaluation (phase I) during a week with detailed clinical history, cranial magnetic resonance imaging, monitoring EEG and video. Ictal and interictal SPECT were performed using a fast rotating brain dedicated camera (TOMOMATIC 564) in a quiet and normally illuminated room with controlled EEG (interictal) or video EEG (ictal); Scanning was started one hour after injection of ECD Tc administered in IV a few seconds after the electrical onset seizure. Slices parallel to the long axis of the temporal lobe were reconstructed. SPECT images were evaluated after normalisation. This study shows that

Technetium HMPAO SPECT study in dementia with Lewy bodies, Alzheimer's disease and idiopathic Parkinson's disease.

UNLABELLED: The aim of this study was to compare the regional cerebral blood flow measurements studied by SPECT in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) to determine the contribution of SPECT to the differential diagnosis of these two diseases. METHODS: SPECT analysis with 99mTc-hexamethyl propyleneamine oxime (HMPAO) was performed in 20 patients with probable DLB, 20 patients with probable AD and 20 patients with idiopathic Parkinson's disease (IPD). Ten pairs of regions of interest were analyzed. Tracer uptake was expressed as a corticocerebellar activity ratio. RESULTS: Compared with IPD, in the DLB group there was a global decrease of HMPAO uptake in cortical regions of interest except in the posterior frontal and occipital regions; in the AD group there was limited left temporal and parietal hypoperfusion. In the DLB group, frontal HMPAO uptake was significantly lower than in the AD group. Two predictive scores were established by a factorial discriminant analysis from six left cortical indices (medial frontal, lateral frontal, posterior frontal, temporoparietal, parietal and parietooccipital) and the Mini-Mental State Examination, which correctly classified 53 of 60 patients (88%) (DLB, 18 of 20; AD, 16 of 20; IPD, 19 of 20). CONCLUSION: These findings indicate the presence of diffuse cortical abnormalities in DLB and suggest that SPECT may be useful in discriminating in vivo DLB from AD, revealing mainly frontal hypoperfusion in the former group. We estimate that SPECT study increases the possibility of separating DLB and AD because both disorders share different patterns of cerebral blood flow abnormality.

Immunochemical detection of egg-white antigens and allergens in meat products.

BACKGROUND: The purpose of this study was to detect antigens and allergens in egg-white byproduct ingredients and after their incorporation in processed pork meat pastes. Commercially prepared foods may have potentially allergenic ingredients (egg, milk, soybean, wheat, and peanut) added in processing. Since allergic patients may react to unidentified ingredients, it is important to assess the allergenic potency of these food proteins added during processing. Egg white was chosen as an experimental model, since egg is one of the most prevalent allergens in food hypersensitivity. METHODS: Experimental pork meat pastes containing egg white underwent pasteurization and sterilization. Ingredients derived from egg-white or paste extracts were isoelectrofocused and then blotted onto cyanogen bromide-activated nitrocellulose membranes. Egg-white antigens were identified in ingredients and in meat products with rabbit anti-egg-white antiserum by isoelectric focusing immunoblotting. Allergens were identified with sera from sensitized patients. A sensitive ELISA test was developed to detect egg-white proteins in raw, pasteurized, and sterilized meat products. RESULTS: Antigens and allergens in four egg-white byproducts were detected. Egg-white antigens were detectable in all ingredients and meat pastes by ELISA. Allergens were detected in ingredients and in raw and pasteurized products by immunoprint techniques and ELISA. CONCLUSIONS: Masked egg-white allergens are recognized by human serum IgE after pasteurization. Egg-white antigens are detectable in sterilized meat by ELISA techniques. Ingestion of processed foods could entail a risk of allergic reactions for sensitized consumers.