Embryo Microinjection of Selenomethionine Reduces Hatchability and Modifies Oxidant Responsive Gene Expression in Zebrafish.

In previous studies we demonstrated that exposure to selenomethionine (SeMet) causes developmental toxicities in zebrafish (Danio rerio). The objectives of this study were to establish a dose-response relationship for developmental toxicities in zebrafish after embryo microinjection of Se (8, 16 or 32 µg/g dry mass of eggs) in the form of SeMet, and to investigate potential underlying mechanism(s) of SeMet-induced developmental toxicities. A dose-dependent increase in frequencies of mortality and total deformities, and reduced hatchability were observed in zebrafish exposed to excess Se via embryo microinjection. The egg Se concentration causing 20% mortality was then used to investigate transcript abundance of proteins involved in antioxidant protection and methylation. Excess Se exposure modified gene expression of oxidant-responsive transcription factors (nuclear factor erythroid 2-related factor nrf2a and nrf2b), and enzymes involved in cellular methylation (methionine adenosyltransferase mat1a and mat2ab) in zebrafish larvae. Notably, excess Se exposure up-regulated transcript abundance of aryl hydrocarbon receptor 2 (ahr2), a signalling pathway involved in the toxicity of dioxin-related compounds. Our findings suggest that oxidative stress or modification of methylation, or a combination of these mechanisms, might be responsible for Se-induced developmental toxicities in fishes.

Mercury and cortisol in Western Hudson Bay polar bear hair.

Non-invasive methods of assessing animal health and life history are becoming increasingly popular in wildlife research; hair samples from polar bears (Ursus maritimus), are being used to study an ever broader range of anthropogenic and endocrine compounds. A number of contaminants are known to disrupt endocrine function in polar bears. However, the relationship between mercury and cortisol remains unknown, although mercury is an endocrine disruptor in other species. Here, we examine the relationship between concentrations of cortisol and total mercury (THg) analyzed in guard hair from 378 polar bears (184 females, 194 males) sampled in Western Hudson Bay, 2004-2012. The difference in mean cortisol concentration between female (0.8 ± 0.6 pg/mg) and male (0.7 ± 0.5 pg/mg) polar bears bordered on significance (p = 0.054). However, mean mercury concentration was significantly greater (p = 0.009) in females (4.7 ± 1.4 µg/g) than males (4.3 ± 1.2 µg/g). Hair cortisol in males was significantly influenced by mercury, age, and fatness, as well as interactions between mercury and year, mercury and fatness, and year and fatness (all: p < 0.03) (multiple regression analysis, whole model: r(2) = 0.14, F(7,185) = 4.43, p = 0.0001). Fatness was the only significant variable in the multiple regression analysis for females (r(2) = 0.06, F(1,182) = 13.0, p = 0.0004). In conclusion, a significant, but complex, relationship was found between mercury and cortisol concentrations in hair from male, but not female, polar bears.

A randomized trial of the effects of nebulized albuterol on pulmonary edema in brain-dead organ donors.

Donor lung utilization rates are persistently low primarily due to donor lung dysfunction. We hypothesized that a treatment that enhances the resolution of pulmonary edema by stimulating the rate of alveolar fluid clearance would improve donor oxygenation and increase donor lung utilization. We conducted a randomized, blinded, placebo-controlled trial of aerosolized albuterol (5mg q4h) versus saline placebo during active donor management in 506 organ donors.The primary outcome was change in oxygenation arterial partial pressure of oxygen/fraction of inspired oxygen [PaO2/FiO2] from enrollment to organ procurement.The albuterol (n»260) and placebo (n»246)groups were well matched for age, gender, ethnicity,smoking, and cause of brain death. The change in PaO2/FiO2 from enrollment to organ procurement did not differ between treatment groups (p»0.54) nor did donor lung utilization (albuterol 29% vs. placebo 32%,p»0.44). Donors in the albuterol versus placebo groups were more likely to have the study drug dose reduced (13% vs. 1%, p<0.001) or stopped (8% vs. 0%,p<0.001) for tachycardia. In summary, treatment with high dose inhaled albuterol during the donor management period did not improve donor oxygenation or increase donor lung utilization but did cause tachycardia.High dose aerosolized albuterol should not be used in donors to enhance the resolution of pulmonary edema.

Poplar genetic engineering: promoting desirable wood characteristics and pest resistance.

Worldwide biomass demand for industrial applications, especially for production of biofuels, is increasing. Extended cultivation of fast growing trees such as poplars may contribute to satisfy the need for renewable resources. However, lignin, which constitutes about 20-30% of woody biomass, renders poplar wood recalcitrant to saccharification. Genetic engineering of the enzymes of the lignification pathway has resulted in drastic decreases in lignin and greatly improved the carbohydrate yield for ethanol fermentation. While uncovering key enzymes for lignification facilitated rapid biotechnological progress, knowledge on field performance of low-lignin poplars is still lagging behind. The major biotic damage is caused by poplar rust fungi (Melampsora larici-populina), whose defense responses involve lignification and production of phenolic compounds. Therefore, manipulation of the phenylpropanoid pathway may be critical and should be tightly linked with new strategies for improved poplar rust tolerance. Emerging novel concepts for wood improvement are discussed.

Isoprene function in two contrasting poplars under salt and sunflecks.

In the present study, biogenic volatile organic compound (BVOC) emissions and photosynthetic gas exchange of salt-sensitive (Populus x canescens (Aiton) Sm.) and salt-tolerant (Populus euphratica Oliv.) isoprene-emitting and non-isoprene-emitting poplars were examined under controlled high-salinity and high-temperature and -light episode ('sunfleck') treatments. Combined treatment with salt and sunflecks led to an increased isoprene emission capacity in both poplar species, although the photosynthetic performance of P. × canescens was reduced. Indeed, different allocations of isoprene precursors between the cytosol and the chloroplast in the two species were uncovered by means of (13)CO2 labeling. Populus × canescens leaves, moreover, increased their use of 'alternative' carbon (C) sources in comparison with recently fixed C for isoprene biosynthesis under salinity. Our studies show, however, that isoprene itself does not have a function in poplar survival under salt stress: the non-isoprene-emitting leaves showed only a slightly decreased photosynthetic performance compared with wild type under salt treatment. Lipid composition analysis revealed differences in the double bond index between the isoprene-emitting and non-isoprene-emitting poplars. Four clear metabolomics patterns were recognized, reflecting systemic changes in flavonoids, sterols and C fixation metabolites due to the lack/presence of isoprene and the absence/presence of salt stress. The studies were complemented by long-term temperature stress experiments, which revealed the thermotolerance role of isoprene as the non-isoprene-emitting leaves collapsed under high temperature, releasing a burst of BVOCs. Engineered plants with a low isoprene emission potential might therefore not be capable of resisting high-temperature episodes.

Glucocorticosteroid concentrations in feces and hair of captive caribou and reindeer following adrenocorticotropic hormone challenge.

Climate change and industrial development are contributing to synchronous declines in Rangifer populations across the Arctic. Chronic stress has been implicated as a proximate factor associated with decline in free-ranging populations, but its role in Rangifer is unspecified. Analysis of glucocorticosteroid (GC) concentration in feces, and more recently in hair, is a non-invasive method for monitoring stress in wildlife. Adrenocorticotropic hormone (ACTH) released from the pituitary gland stimulates GC release from the adrenals and can be administered to reflect adrenal activation. In this study, we assessed concentrations of GC metabolites in feces and cortisol in hair of Alaskan caribou (Rangifer tarandus granti) and reindeer (R. t. tarandus) following ACTH treatment. We predicted that ACTH challenge would increase concentrations of fecal GCs, but not hair cortisol because steroid deposited into the hair shaft occurs over an extended period of time (months) and is likely insensitive to acute adrenal stimulation. Adult caribou (n=10; mean age, 6.5 years old) exhibited a peak increase in fecal GCs 8h following a 2 IU/kg dose of ACTH compared to pre-injection concentrations. In contrast, sub-adult reindeer (n=10, 0.8 years old) elicited a diminished response to the same dose. Quadrupling the dose (8 IU/kg) prolonged the fecal GC response in female reindeer, but male reindeer were unresponsive. Hair cortisol was unaffected by a single ACTH challenge. Further investigation is required to ascertain whether subspecific differences in adrenal sensitivity are attributed to age or sex differences, or historical selective pressures from semi-domestication and/or sedentary life cycle in reindeer.

Dietary selenomethionine exposure in adult zebrafish alters swimming performance, energetics and the physiological stress response.

Selenomethionine (Se-Met) is the major form of organoselenium present in food. Early life stages of oviparous vertebrate species, especially fish, are highly susceptible to dietary selenium (Se) exposure; however less is known concerning effects in adults. The present study was designed to investigate behavioral and physiological consequences of dietary Se-Met exposure to adult zebrafish (Danio rerio). Adult fish were fed either control food (1.3µg Se/g, dry weight or dw) or food spiked with varying measured concentrations of Se (3.7, 9.6 and 26.6 µg Se/g, dw) in the form of Se-Met for 60 days at 5% body weight/day ration, and an additional 30-40 days with equal ration (2.5%) of control or Se-Met spiked foods and clean chironomids. At the end of the exposure period, critical swimming speed (Ucrit), oxygen consumption (MO(2)), cost of transport (COT), tail beat amplitude, tail beat frequency, and whole body cortisol, triglyceride and glycogen levels were determined. Significantly reduced Ucrit was observed in fish fed 3.7, 9.6 and 26.6 µg Se/g when compared to control fish. Although MO(2) of fish fed >3 µg Se/g was consistently greater than control fish, those values were not statistically significant. There was no difference in COT among different treatment groups. Tail beat amplitudes of fish fed >3 µg Se/g were lower than control fish, however tail beat frequencies were not altered. Fish fed 3.7, 9.6 and 26.6 µg Se/g had greater whole body triglycerides and glycogen levels than control fish. Fish fed the highest concentration of Se (26.6 µg Se/g) had elevated levels of whole body cortisol compared to control fish. Our results suggest that environmentally relevant dietary Se-Met exposure can alter both behavioral and physiological responses in adult fish, and such consequences could threaten fitness of adult fish in Se impacted aquatic ecosystems.

Prospective memory in patients with juvenile myoclonic epilepsy and their healthy siblings.

OBJECTIVE: Prospective memory (PM) describes the ability to fulfill previously planned intentions and is highly dependent on executive functions. Previous studies have shown deficits in executive functions in patients with juvenile myoclonic epilepsy (JME) and in their unaffected siblings. JME has a strong genetic predisposition and it is hypothesized that cognitive deficits are also genetically determined. The present study aimed at investigating potential differences in PM between patients with JME, their siblings, and healthy controls. METHODS: Nineteen patients with JME, 21 siblings, and 21 healthy controls were examined with a complex PM paradigm allowing us to evaluate the different phases of PM (i.e., intention formation, intention retention, intention initiation, intention execution). RESULTS: Patients with JME and siblings showed specific deficits during intention formation and intention execution of PM. Patients with JME were more impaired than both siblings and healthy controls. Correlation analysis revealed an influence of planning on prospective memory abilities in patients with JME. CONCLUSION: The results of this study support the hypothesis of frontal dysfunctions being part of the epileptic syndrome and therefore genetically determined. As in this study patients with JME are more severely cognitively impaired than their siblings, additional influencing factors, such as side effects of anticonvulsants or cognitive effects of subclinical epileptic discharges, might contribute to patients' performance.

Selenium accumulation in aquatic biota downstream of a uranium mining and milling operation.

Uranium mining and milling operations have the potential to release trace elements such as arsenic, molybdenum, nickel, selenium and uranium and ions (e.g., sulfate, ammonium) into the receiving aquatic ecosystem. The major implication of elevated environmental selenium is its propensity to accumulate in the aquatic food chain, potentially impairing fish reproduction. The objective of this study was to investigate the accumulation of selenium in the major compartments of aquatic ecosystems (lakes) upstream and downstream of a uranium mine in northern Saskatchewan, Canada. Selenium concentrations in aquatic biota were elevated in the exposure lake although water and sediment concentrations were low (0.43 microg/L and 0.54 microg/g dry weight, respectively). Biomagnification of selenium resulted in approximately 1.5 to 6 fold increase in the selenium concentration between plankton, invertebrates and fish. However, no biomagnification was observed between forage and predatory fish. Although some aquatic biota (e.g., forage fish) exceeded the lower limit of the proposed 3 to 11 microg/g (dry weight) dietary toxicity threshold for fish, no adverse effects of selenium could be identified in this aquatic system. Continued environmental monitoring is recommended to avoid potential selenium impacts.

Accumulation of selenium in aquatic systems downstream of a uranium mining operation in northern Saskatchewan, Canada.

The objective of this study was to investigate the accumulation of selenium in lakes downstream of a uranium mine operation in northern Saskatchewan, Canada. Selenium concentrations in sediment and biota were elevated in exposure areas even though water concentrations were low (<5 microg/L). The pattern (from smallest to largest) of selenium accumulation was: periphyton

Tissue-specific HSP70 levels and reproductive physiological responses in fishes inhabiting a metal-contaminated creek.

The 70-kDa stress protein family (HSP70) plays important roles in a variety of physiological processes, including protein chaperoning, protection against apoptosis, steroidogenesis, and general cellular stress responses in vertebrate organisms, and has also been proposed as a biochemical marker of environmental stress, such as toxicant exposure. The objectives of this study were to determine HSP70 protein expression in head kidney, liver, gill, and ovarian tissues and to examine reproductive physiological responses in female fishes exposed chronically to sublethal metal concentrations. Female black bullhead (Ameiurus melas) and bluegill sunfish (Lepomis macrochirus) were collected from Tar Creek, Oklahoma (flowing through the Tri-State mining district) and from a nearby reference creek (Lytle Creek) during spring (prespawning; 26.5 +/- 0.95 degrees C water temperature) and winter (ovarian recrudescence; 4.8 +/- 0.80 degrees C water temperature). Aqueous (dissolved and suspended) concentrations of Cd and Zn and liver concentrations of Cd and Zn in both fish species were significantly greater at Tar Creek compared to Lytle Creek. HSP70 expression was consistently elevated in the head kidney of both fish species collected at Tar Creek in comparison to fish collected from the reference creek. In contrast, no consistent differences were observed in HSP70 expression in liver, gill, or ovarian tissues between sites. Significant seasonal differences were observed in expression of HSP70 in gill tissue of both species, in ovarian and liver tissue of bluegill sunfish and in head kidney of black bullhead. Serum testosterone concentration was significantly reduced in sunfish collected from Tar Creek during winter. Gonadosomatic and hepatosomatic indices were significantly lower in black bullhead collected from Tar Creek during spring, and condition factors were lower in black bullhead collected from Tar Creek during both spring and winter. There was no significant difference in the extent of ovarian follicular cell apoptosis in either species collected during spring. In conclusion, we observed significant tissue specific differences and seasonal variation in expression of HSP70, as well as alterations in circulating testosterone levels in female fish chronically exposed to metals.

No evidence for a susceptibility locus for idiopathic generalized epilepsy on chromosome 5 in families with typical absence seizures.

A recent genome-wide scan revealed suggestive evidence for two susceptibility loci for idiopathic generalized epilepsy (IGE) in the chromosomal regions 5p15 and 5q14-q22 in families with typical absence seizures. The present replication study tested the validity of the tentative IGE loci on chromosome 5. Our study included 99 multiplex families in which at least one family member had typical absence seizures. Parametric and non-parametric multipoint linkage analyses were carried out between the IGE trait and 23 microsatellite polymorphisms covering the entire region of chromosome 5. Multipoint parametric heterogeneity lod scores < -2 were obtained along chromosome 5 when a proportion of linked families greater than 50% was assumed under recessive inheritance and > 60% under dominant inheritance. Furthermore, non-parametric multipoint linkage analyses revealed no hint of linkage throughout the candidate region (P > 0.05). Accordingly, we failed to support previous evidence for common IGE loci on chromosome 5. If there is a susceptibility locus for IGE on chromosome 5 then the size of the effect or the proportion of linked families is too small to detect linkage in the investigated family sample.

Effect of beta-naphthoflavone and dimethylbenz[a]anthracene on apoptosis and HSP70 expression in juvenile channel catfish (Ictalurus punctatus) ovary.

Complex environmental mixtures such as pulp mill effluents and crude oil have been shown to increase ovarian cell apoptosis and affect heat shock protein (HSP) expression in fish. We hypothesize that polyaromatic hydrocarbons (PAH) mediate these effects. To test this hypothesis, we exposed juvenile channel catfish (Ictalurus punctatus) acutely to the aryl hydrocarbon receptor (AhR) agonists, beta-naphthoflavone (BNF; 75 mg/kg) or the model PAH, dimethylbenz[a]anthracene (DMBA; 50 mg/kg) via intraperitoneal injection. Apoptotic DNA fragmentation and HSP70 expression were determined in ovary and liver. Hepatic cytochrome P450 1A (CYP1A) was significantly induced, confirming that BNF and DMBA had distributed to internal organs and stimulated AhR. At 96 h post-injection, BNF and DMBA significantly increased apoptosis and decreased HSP70 expression in juvenile catfish ovaries. Although primary oocytes underwent the greatest rates of apoptosis compared to early or late vitellogenic follicles in all treatment groups, the cell type undergoing increased rates of apoptosis after BNF or DMBA exposure was not clear using terminal deoxynucleotidyl transferase (TdT)-mediated deoxyUTP nick end labeling (TUNEL). There was a significant negative relationship between expression of HSP70 and apoptosis in juvenile channel catfish ovaries. This differed from liver of these fish which did not exhibit increased apoptosis and instead increased hepatic HSP70 expression at 96 h post-injection. However, DMBA had no effect on apoptosis or HSP70 levels in more reproductively mature juvenile fish that were housed at a lower water temperature. This may be due to a developmental or temperature-dependent component to these responses. We propose that the decrease in ovarian HSP70 expression in response to BNF and DMBA may be causally related to the increase in ovarian cell apoptosis. Further experiments using a full time course, dose-response and methods to confirm that AhR is a direct mediator of these effects are required.

Epilepsy with grand mal on awakening and sleep-waking cycle.

Awakening epilepsy (AE) is an age related syndrome of idiopathic generalized epilepsy (IGE) characterized by generalized tonic clonic seizures (GTCS) occurring predominantly on awakening (independent of the time of day) or at leisure time (almost at evening). The GTCS can be the only symptom or they can be combined with the other subsyndromes of IGE in childhood or adolescence. The EEG shows the characteristics of IGE (generalized spike wave frequent, foca1 abnormalities rare, photosensitivity increased). The common denominator of external seizures precipitating influences is lack of sleep. The sleep habits of patients with AE who could roughly be characterized as late sleepers and late risers may dispose them to a chronic sleep deficit. Polygraphic studies indicated that their sleep is more unstable and subject to external influences. Microstructural sleep analysis confirms the presence of a disturbance of sleep stability in patients with IGE. Furthermore, it clearly shows that in the prototype of AE, the juvenile myoclonic epilepsy, the epileptiform activity during non-REM sleep is correlated with the arousal phase of the so called cyclic alternating pattern indicating that even in the smallest sleep-waking oscillations awakening is the most sensitive part.

Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures. European Levetiracetam Study Group.

PURPOSE: To evaluate the efficacy and tolerability of levetiracetam (LEV, Keppra) as add-on therapy in patients with refractory partial seizures. METHODS: In this European multicenter, double-blind, randomized, placebo-controlled trial, LEV (500 or 1,000 mg twice daily) was compared with placebo as add-on therapy in 324 patients with uncontrolled simple or complex partial seizures, or both, with or without secondary generalization. After enrollment, three parallel groups were assessed during a baseline period of 8 or 12 weeks, followed by a 4-week titration interval and a 12-week evaluation period. RESULTS: LEV significantly decreased partial seizure frequency compared with placebo. A reduction in seizure frequency of > or =50% occurred in 22.8% of patients in the 1,000-mg group and 31.6% of patients in the 2,000-mg group, compared with 10.4% of patients in the placebo group. Administration of LEV did not affect plasma concentrations of concomitant antiepileptic drugs or alter vital signs or laboratory parameters. No significant difference in the incidence of adverse events was observed between treatment groups (70.8% for the 1,000-mg group and 75.5% for the 2,000-mg group), or between the LEV and placebo groups (73.2% for placebo group). The most commonly reported adverse effects in the LEV group were asthenia, headache, and somnolence. CONCLUSIONS: The antiepileptic efficacy and tolerability of LEV (1,000 mg/d and 2,000 mg/d, administered in two divided doses) as add-on therapy was established in patients with refractory partial seizures in this clinical study.

Genome search for susceptibility loci of common idiopathic generalised epilepsies.

Genetic factors play a major role in the aetiology of idiopathic generalised epilepsies (IGEs). The present genome scan was designed to identify susceptibility loci that predispose to a spectrum of common IGE syndromes. Our collaborative study included 130 IGE-multiplex families ascertained through a proband with either an idiopathic absence epilepsy or juvenile myoclonic epilepsy, and one or more siblings affected by an IGE trait. In total, 413 microsatellite polymorphisms were genotyped in 617 family members. Non-parametric multipoint linkage analysis, using the GeneHunter program, provided significant evidence for a novel IGE susceptibility locus on chromosome 3q26 (Z(NPL) = 4.19 at D3S3725; P = 0.000017) and suggestive evidence for two IGE loci on chromosome 14q23 (Z(NPL) = 3.28 at D14S63; P = 0.000566), and chromosome 2q36 (Z(NPL) = 2.98 at D2S1371; P = 0.000535). The present linkage findings provide suggestive evidence that at least three genetic factors confer susceptibility to generalised seizures in a broad spectrum of IGE syndromes. The chromosomal segments identified harbour several genes involved in the regulation of neuronal ion influx which are plausible candidates for mutation screening.

Genetic variation of the human mu-opioid receptor and susceptibility to idiopathic absence epilepsy.

Pharmacological and autoradiological studies suggest that mu-opioid receptor (OPRM) mediated neurotransmission is involved in the generation of absence seizures. Mutation screening of the human OPRM gene identified a common amino acid substitution polymorphism (Asn40Asp) that differentially modulates the binding affinity of beta-endorphin and signal transduction of the receptor. The present association study tested the candidate gene hypothesis that the Asn40Asp substitution polymorphism in the N-terminal OPRM domain confers genetic susceptibility to idiopathic absence epilepsy (IAE). The genotypes of the Asn40Asp polymorphism were assessed by allele-specific polymerase chain reaction in 72 German IAE patients and in 340 ethnically matched control subjects. The frequency of the Asp40 allele was significantly increased in the IAE patients [f(Asp40) = 0.139] compared to the controls [f(Asp40) = 0.078; chi2 = 5.467, df = 1, P = 0.019; OR = 2.03; 95%-CI: 1.12-3.68]. This allelic association suggests that the functional Asp40 variant of OPRM modulates neuronal excitability underlying the epileptogenesis of IAE.

Elevated ovarian and thymic cell apoptosis in wild cotton rats inhabiting petrochemical-contaminated terrestrial ecosystems.

The objective of this study was to determine the rates of apoptotic cell death in ovary and thymus collected from wild female cotton rats (Sigmodon hispidus) inhabiting five petrochemical-contaminated and five ecologically matched reference sites in Oklahoma. Overall comparison of reference and contaminated sites, using individual sites as replicates, revealed a significantly increased rate of ovarian cell apoptosis in cotton rats inhabiting contaminated sites. In comparison to rats from reference sites, the number of uterine scars was lower in rats collected from the contaminated sites. There were no significant differences in the percentage of atretic follicles among animals collected from reference and contaminated sites. The rate of thymocyte apoptosis was elevated at one of five contaminated sites, although the overall rate of thymocyte apoptosis was not significantly different when comparing all sites. To our knowledge, this is the first study documenting elevated rates of ovarian and thymic cell apoptosis in wild mammals exposed chronically to environmental toxicants.

Association analysis of a regulatory promoter polymorphism of the PAX-6 gene with idiopathic generalized epilepsy.

The PAX-6 gene is a member of the paired-box-containing (PAX) gene family, encoding a transcriptional activator, that plays an important role in the development of the central nervous system. The present association study tested the hypothesis that length variation of a novel regulatory dinucleotide repeat polymorphism in the promoter region of the PAX-6 gene (PAX-6 gene-linked polymorphic region, PAX-6LPR) confers susceptibility to the epileptogenesis of common subtypes of idiopathic generalized epilepsy (IGE). The repeat length of the regulatory dinucleotide repeat polymorphism was assessed in 354 German control subjects and 125 German IGE patients, comprising 70 patients with juvenile myoclonic epilepsy (JME) and 55 patients with an idiopathic absence epilepsy (IAE). The allelic distribution of the PAX-6LPR did not deviate significantly between the controls and the IGE patients (Wilcoxon Rank-Sum test: P > 0.76), or both subgroups of either JME patients (P > 0.78) or IAE patients (P > 0.87). Our results do not provide evidence that length variation of the polymorphic dinucleotide sequence in the PAX-6LPR contributes a frequent and relevant effect to the pathogenesis of common subtypes of IGE.