Biomedical subjects

M Hecker

Publications and source records attributed to M Hecker.

At least 19 recordsLinked to original sources

PubMed2006

Tolerance, safety and efficacy of Hedera helix extract in inflammatory bronchial diseases under clinical practice conditions: a prospective, open, multicentre postmarketing study in 9657 patients.

In this postmarketing study 9657 patients (5181 children) with bronchitis (acute or chronic bronchial inflammatory disease) were treated with a syrup containing dried ivy leaf extract. After 7 days of therapy, 95% of the patients showed improvement or healing of their symptoms. The safety of the therapy was very good with an overall incidence of adverse events of 2.1% (mainly gastrointestinal disorders with 1.5%). In those patients who got concomitant medication as well, it could be shown that the additional application of antibiotics had no benefit respective to efficacy but did increase the relative risk for the occurrence of side effects by 26%. In conclusion, it is to say that the dried ivy leaf extract is effective and well tolerated in patients with bronchitis. In view of the large population considered, future analyses should approach specific issues concerning therapy by age group, concomitant therapy and baseline conditions.

Adolescent↗

PubMed2006

Sediment TCDD-EQs and EROD and MROD activities in Ranid frogs from agricultural and nonagricultural sites in Michigan (USA).

In vitro studies have demonstrated atrazine-mediated induction of 7-ethoxyresorufin O-deethylase (EROD) activity. EROD is an enzyme active in the metabolism of many compounds, including many xenobiotics. These studies have suggested that atrazine may affect reproductive function by altering steroid metabolism. The goal of this study was to determine whether relationships could be detected between measured atrazine concentrations in surface waters and the liver-somatic index (LSI) and EROD and 7-methoxyresorufin O-deethylase (MROD) activities in the livers of ranid frogs. In addition, sediment dioxin toxic equivalents (TCDD-EQs) were determined using the H4IIE-luc cell bioassay. Adult and juvenile green frogs (Rana clamitans), bullfrogs (R. catesbeiana), and Northern leopard frogs (R. pipiens) were collected from areas with extensive corn cultivation and areas where there was little agricultural activity in south central Michigan in the summer of 2003. Atrazine concentrations at nonagricultural sites ranged from less than the limit of quantification (0.17 microg atrazine/L) to 0.23 microg atrazine/L and did not exceed 1.2 microg atrazine/L at agricultural sites. Sediment TCDD-EQs were measurable only at one agricultural site. Of the measured parameters, only LSI values in adult male frogs differed significantly between agricultural and nonagricultural sites, with greater values observed at agricultural sites. In green frogs, EROD and MROD activities were measurable in both adult and juvenile frogs and were similar among sites. Median EROD activities ranged from 13 to 21 pmol/min/mg protein in adult male green frogs and from 5 to 13 pmol/min/mg protein in adult female green frogs. Juvenile frogs had greater EROD and MROD activities than adult frogs. Bullfrogs and leopard frogs had greater activities than did green frogs. Atrazine concentrations were significantly and negatively correlated with MROD activity in adult male green frogs (Spearman R = -0.800). LSI and EROD and MROD activities of adult female or juvenile green frogs were not significantly correlated with atrazine concentrations. These results suggest that atrazine does not appear to have a consistent association with EROD or MROD activities in wild-caught green frogs.

Agriculture↗

PubMed2006

Plasma steroid hormone concentrations, aromatase activities and GSI in ranid frogs collected from agricultural and non-agricultural sites in Michigan (USA).

The triazine herbicide atrazine has been hypothesized to disrupt sexual development in frogs by up-regulating aromatase activity, resulting in greater estradiol (E2) concentrations and causing feminization in males. The goal of this study was to collect native ranid frogs from atrazine-exposed ponds and determine whether relationships exist between measured atrazine concentrations and the gonadosomatic index (GSI), plasma concentrations of testosterone (T), E2 or 11-ketotestosterone (KT), or with aromatase activity. In the summer of 2002 and 2003, adult and juvenile green frogs (Rana clamitans), bullfrogs (R. catesbeiana) and Northern leopard frogs (R. pipiens) were collected from areas with extensive corn cultivation and areas where there was little agricultural activity in south-central Michigan. Atrazine concentrations were below the limit of quantification at non-agricultural sites. Atrazine concentrations did not exceed 2 microg/L at most agricultural sites, but a concentration of 250 microg atrazine/L was measured in one sample from one site in 2002. Plasma steroid concentrations varied among locations. Aromatase activity was measurable in less than 11% of testes in adult males, and in less than 4% of testes in juvenile males. Median aromatase activities in ovaries of adult females ranged from 3 to 245 pmol/h/mg protein, and maximum activities were 2.5-fold greater in juveniles than in adults. Atrazine concentrations were not significantly correlated with any of the parameters measured in this study. These results indicate that atrazine does not up-regulate aromatase in green frogs in the wild, and does not appear to affect plasma steroid hormone concentrations.

Animals↗

PubMed2006

[Rheumatoid arthritis and cardiovascular complications].

Rheumatoid arthritis is associated with increased morbidity and mortality due to cardiovascular events. Elevated concentrations of acute-phase proteins and cytokines and endothelial dysfunction, demonstrated also by lack of traditional risk factors, play an important role in these complications. Antirheumatic drug treatment can modify the frequency and severity of cardiovascular events.

Antirheumatic Agents↗

PubMed2006

Inhibition of carotis venous bypass graft disease by intraoperative nucleic acid-based therapy in rabbits.

BACKGROUND: Bypass graft stenosis after venous revascularisation procedures is characterised by massive neointimal and vascular smooth muscle cell proliferation triggered via endothelin-1 synthesis in the vessel wall. Decoy oligodesoxynucleotides (ODN) against the transcription factor activator protein-1 (AP-1) inhibits pre-pro-endothelin-1 expression. METHODS: In 20 rabbits, an end-to-side jugular vein bypass to the carotid artery was performed: (group A) 8 grafts were treated with consensus AP-1 decoy ODN, (group B) 8 with mutated control ODN and (group C) 4 received no treatment. Explantation, histomorphometric and immunohistochemical evaluation was performed after 28 days. RESULTS: Median intimal thickness of groups: (A) 28.3 microm, (B) 48.4 microm, (C) 71.1 microm. The decoy ODN-treated group showed a significant reduction of neointima formation ( P = 0.029) and a downregulation of the endothelin receptor. CONCLUSIONS: In this model, neointima formation was reduced by local transfection with consensus decoy ODN against AP-1. Endothelin A and B receptor expression is downregulated. Molecular target nucleic acid-based therapies seem to be a future means of overcoming neointima proliferation in pressure-induced venous graft failure. Intraoperative local application makes it easy to use in routine revascularisation procedures.

Animals↗

PubMed2006

Mapping the pathways to staphylococcal pathogenesis by comparative secretomics.

The gram-positive bacterium Staphylococcus aureus is a frequent component of the human microbial flora that can turn into a dangerous pathogen. As such, this organism is capable of infecting almost every tissue and organ system in the human body. It does so by actively exporting a variety of virulence factors to the cell surface and extracellular milieu. Upon reaching their respective destinations, these virulence factors have pivotal roles in the colonization and subversion of the human host. It is therefore of major importance to obtain a clear understanding of the protein transport pathways that are active in S. aureus. The present review aims to provide a state-of-the-art roadmap of staphylococcal secretomes, which include both protein transport pathways and the extracytoplasmic proteins of these organisms. Specifically, an overview is presented of the exported virulence factors, pathways for protein transport, signals for cellular protein retention or secretion, and the exoproteomes of different S. aureus isolates. The focus is on S. aureus, but comparisons with Staphylococcus epidermidis and other gram-positive bacteria, such as Bacillus subtilis, are included where appropriate. Importantly, the results of genomic and proteomic studies on S. aureus secretomes are integrated through a comparative "secretomics" approach, resulting in the first definition of the core and variant secretomes of this bacterium. While the core secretome seems to be largely employed for general housekeeping functions which are necessary to thrive in particular niches provided by the human host, the variant secretome seems to contain the "gadgets" that S. aureus needs to conquer these well-protected niches.

Bacterial Proteins↗

PubMed2005

Atrazine concentrations, gonadal gross morphology and histology in ranid frogs collected in Michigan agricultural areas.

The triazine herbicide atrazine has been suggested to be a potential disruptor of normal sexual development in male frogs. The goals of this study were to collect native ranid frogs from sites in agricultural and non-agricultural areas and determine whether hypothesised atrazine effects on the gonads could be observed at the gross morphological and histological levels. Juvenile and adult green frogs (Rana clamitans), bullfrogs (R. catesbeiana) and leopard frogs (R. pipiens) were collected in the summers of 2002 and 2003. Atrazine concentrations were below the limit of quantification at non-agricultural sites, and concentrations did not exceed 2 microg/L at most agricultural sites. One concentration greater than 200 microg atrazine/L was measured once at one site in 2002. Hermaphroditic individuals with both male and female gonad tissue in either one or both gonads, were found at a low incidence at both non-agricultural and agricultural sites, and in both adults and juveniles. Testicular oocytes (TO) were found in male frogs at most of the sites, with the greatest incidence occurring in juvenile leopard frogs. TO incidence was not significantly different between agricultural and non-agricultural sites with the exception of juveniles collected in 2003. Atrazine concentrations were not significantly correlated with the incidence of hermaphroditism, but maximum atrazine concentrations were correlated with TO incidence in juvenile frogs in 2003. However, given the lack of a consistent relationship between atrazine concentrations and TO incidence, it is more likely the TOs observed in this study result from natural processes in development rather than atrazine exposure.

Agrochemicals↗

PubMed2005

Genome-wide mRNA profiling in glucose starved Bacillus subtilis cells.

In this study global changes in gene expression were monitored in Bacillus subtilis cells entering stationary growth phase owing to starvation for glucose. Gene expression was analysed in growing and starving cells at different time points by full-genome mRNA profiling using DNA macroarrays. During the transition to stationary phase we observed extensive reprogramming of gene expression, with approximately 1,000 genes being strongly repressed and approximately 900 strongly up-regulated in a time-dependent manner. The genes involved in the response to glucose starvation can be assigned to two main classes: (i) general stress/starvation genes which respond to various stress or starvation stimuli, and (ii) genes that respond specifically to starvation for glucose. The first class includes members of the sigma(B)-dependent general stress regulon, as well as 90 vegetative genes, which are strongly down regulated in the course of the stringent response. Among the genes in the second class, we observed a decrease in the expression of genes encoding proteins required for glucose uptake, glycolysis and the tricarboxylic acid cycle. Conversely, many carbohydrate utilisation systems that depend on phosphotransferase systems (PTS) or ABC transporters were activated. The expression of genes required for utilisation or generation of acetate indicates that acetate constitutes an important energy source for B. subtilis during periods of glucose starvation. Finally, genome wide mRNA profiling data can be used to predict new metabolic pathways in B. subtilis. Thus, our data suggest that glucose-starved cells are able to degrade branched-chain fatty acids to pyruvate and succinate via propionyl-CoA using the methylcitrate pathway. This pathway appears to link lipid degradation to gluconeogenesis in glucose-starved cells.

Bacillus subtilis↗

PubMed2005

CD40 antisense oligonucleotide inhibition of trinitrobenzene sulphonic acid induced rat colitis.

BACKGROUND: CD154/CD40 interactions play a pivotal role both in humoral and cellular immune responses. Their involvement in the pathogenesis of chronic inflammatory bowel disease (IBD) has been revealed by increased expression of CD40 and CD154 in the inflamed mucosa of patients and the therapeutic effects of anti-CD154 antibodies in experimental colitis. Because of adverse side effects however, the use of such antibodies in patients with IBD may be limited. AIMS: An alternative approach to blocking CD154/CD40 interactions by employing a CD40 antisense oligonucleotide (ODN) was explored. RESULTS: After sequencing of the rat CD40 gene, five antisense ODNs were designed, of which one (rAS3) effectively downregulated CD40 expression in rat vascular smooth muscle cells as well as the subsequent changes in gene expression in response to CD40 stimulation. The therapeutic potency of rAS3 was evaluated in the 2,4,6-trinitrobenzene sulphonic acid (TNBS) induced colitis model of the rat. Single intracolonic injection of a liposomal formulation of rAS3 either prior to or post colitis induction markedly suppressed the inflammatory reaction in these animals monitored both macroscopically and microscopically over one week, while application of a scrambled control ODN had no such effects. Moreover, reverse transcription-polymerase chain reaction analyses revealed reduced expression of vascular cell adhesion molecule 1, interleukin 12 p40, and monocyte chemoatractive protein 1 in the inflamed mucosa, which in turn may have contributed to the decrease in leucocyte infiltration judged by immunohistochemistry. CONCLUSIONS: These results suggest that CD40 antisense ODNs effectively interfere with CD154/CD40 interactions in vivo and, therefore, may provide a novel approach to the treatment of patients with chronic IBD.

Animals↗

PubMed2004

A proteomic approach to understanding the development of multidrug-resistant Candida albicans strains.

Resistance of the pathogenic yeast Candida albicans to the antifungal agent fluconazole is often caused by the overexpression of genes that encode multidrug efflux pumps ( CDR1, CDR2, or MDR1). We have undertaken a proteomic approach to gain further insight into the regulatory network controlling efflux pump expression and drug resistance in C. albicans. Three pairs of matched fluconazole-susceptible and resistant clinical C. albicans isolates, in which drug resistance correlated with stable activation of MDR1 or CDR1/2, were analyzed for differences in their protein expression profiles. In two independent, MDR1-overexpressing, strains, additional up-regulated proteins were identified, which are encoded by the YPR127 gene and several members of the IFD ( YPL088) gene family. All are putative aldo-keto reductases of unknown function. These proteins were not up-regulated in a fluconazole-resistant strain that overexpressed CDR1 and CDR2 but not MDR1, indicating that expression of the various efflux pumps of C. albicans is controlled by different regulatory networks. To investigate the possible role of YPR127 in the resistance phenotype of the clinical isolates, we constitutively overexpressed the gene in a C. albicans laboratory strain. In addition, the gene was deleted in a C. albicans laboratory strain and in one of the drug-resistant clinical isolates in which it was overexpressed. Neither forced overexpression nor deletion of YPR127 affected the susceptibility of the strains to drugs and other toxic substances, suggesting that the regulatory networks which control the expression of efflux pumps in C. albicans also control genes involved in cellular functions not related to drug resistance.

Antifungal Agents↗

PubMed2004

Comparison of the annealing behavior of thin Ta films deposited onto Si and SiO2 substrates.

Structural changes at annealing temperatures (T(an)) of 500-1,100 degrees C were investigated for thin Ta films which were sputter-deposited onto pure Si substrates and onto thermally oxidized Si. In the as-deposited state, the Ta layers predominantly consist of metastable tetragonal beta-Ta, whereby the [001] texture is independent of the substrate material. At lower annealing temperatures, the microstructural evolution is essentially the same for both Ta films. Incorporation of O atoms causes an increase of the intrinsic compressive stress, and diffusion of C atoms into the Ta layer leads to the formation of Ta(2)C. Additionally, a partial transformation of the original beta-Ta phase into a second phase with tetragonal unit cell (denoted as beta'-Ta) occurs. For the Ta/Si system, the formation of a Ta-Si intermixing layer is initiated at T(an)=550 degrees C, and nucleation of crystalline TaSi(2) occurs at T(an)=620 degrees C. The formation of a second Ta silicide was not detected up to T(an)=900 degrees C. In the case of the Ta film deposited onto the SiO(2) substrate, the metastable beta-Ta and the beta'-Ta transform completely into the thermodynamically stable cubic alpha-Ta at T(an)=750 degrees C. A marked reaction with the substrate indicated by the formation of Ta(2)O(5) and Ta(5)Si(3) occurs at T(an)=1,000 degrees C.

Alloys↗

PubMed2004

Continuous cytomegalovirus seroconversion in a large group of healthy blood donors.

BACKGROUND AND OBJECTIVES: Transmission of cytomegalovirus (CMV) to seronegative, immunocompromised recipients can cause serious and fatal complications. Although the seroprevalence of CMV is high, the risk of primary CMV infection among healthy blood donors has not yet been analysed in a large population. MATERIALS AND METHODS: We developed an algorithm to determine the rate of CMV seroconversion in an overall cohort of 24,260 subjects who donated 176,474 blood units during an 11-year observation period. RESULTS: We detected CMV seroconversion in all relevant age groups (18-60 years) with an overall seroconversion rate of 0.55% per year. Both CMV seroconversion and seroprevalence occurred more frequently in female donors (P = 0.02 and P < 0.001, respectively). We identified 30-35-year-old blood donors as the group with the highest rate of CMV seroconversion per year (1.33% vs. 0.46%; P < 0.0001). CONCLUSIONS: We conclude that the risk of primary CMV infection is a continuous lifelong event and correlates with age and female gender.

Adolescent↗

PubMed2004

[Tolerability of Icelandic moss lozenges in upper respiratory tract diseases - multicentric drug monitoring study with 3,143 children].

BACKGROUND AND OBJECTIVE: Icelandic moss is a medical herb with therapeutic efficacy in inflammatory airway diseases. Although preparations based on the extract of this lichen have been marketed since the 19th century, their tolerability has not yet been investigated systematically. PATIENTS AND METHODS: The tolerability of Isla-Moos and Isla-Mint lozenges and the changes of clinical symptoms during treatment were investigated in a post-marketing surveillance study performed in 300 predominantly pediatric practices in Germany. The preparations contained 80 and 100 mg, respectively, of an aqueous Icelandic moss extract. 3,143 children between 4 and 12 years of age who suffered from upper respiratory tract diseases received Isla-Moos (n = 1,848) or Isla-Mint (n = 1,295) over a period of 1-2 weeks; 61% of the children received 4-6 lozenges per day. Tolerability was evaluated by assessing adverse drug reactions (ADRs). Treatment success was assessed globally by the investigators and the patients' parents. The parents were also asked to rate their children's symptoms before and after treatment. RESULTS: During the period of observation, 73 adverse events, most of which were related to the basic disease, were reported in 57 children (1.8%). In 6 children (0.2%) and 7 events (2x itching, 2x nausea, 1x abdominal pain, 1x heartburn, 1x burning in the mouth) a causal relationship with Icelandic moss extract could not be excluded, so that they were evaluated as ADRs. All ADRs subsided spontaneously during the period of observation. The incidence of ADRs was 1 event in 3,008 (95% confidence interval: 1,504-7,019) treatment days. As regards clinical symptoms, 39% of the children were fully recovered and another 55% were improved by the end of the period of observation. CONCLUSIONS: During treatment of 4- to 12-year-old children with Isla-Moos and Isla-Mint lozenges only isolated, trivial, and transient adverse drug reactions were observed. The results thus confirm the good tolerability of both drugs and support a favorable risk-benefit assessment.

Bryophyta↗

PubMed2004

Proteomic signatures for daunomycin and adriamycin in Bacillus subtilis.

The influence of the two anthracyclin antibiotics daunomycin and adriamycin on the proteome of Bacillus subtilis was investigated. They intercalate in the double helix causing strand breaks. Both compounds induce proteins related to DNA damage and oxidative stress as indicated by the induction of some members of the PerR and the DinR-regulon. The mild induction of some members of the HrcA- and the CtsR-regulon may indicate protein oxidation as well. Furthermore, an influence on the sigmaB-dependent general stress response was shown. These data show that the proteomic signature is a valuable experimental tool for a comprehensive evaluation of the action of different drugs.

Anti-Bacterial Agents↗

PubMed2003

Patterns of protein carbonylation following oxidative stress in wild-type and sigB Bacillus subtilis cells.

Oxidative stress causes damage to nucleic acids, membrane lipids and proteins. One striking effect is the metal-catalyzed, site-specific carbonylation of proteins. In the gram-positive soil bacterium Bacillus subtilis, the PerR-dependent specific stress response and the sigmaB-dependent general stress response act together to make cells more resistant to oxidative stress. In this study, we analyzed the carbonylation of cytoplasmic proteins in response to hydrogen peroxide stress in B. subtilis. Furthermore, we asked whether the sigmaB-dependent response to oxidative stress also confers protection against protein carbonylation. To monitor the amount and specificity of protein damage, carbonyls were derivatized with 2,4-dinitrophenylhydrazine, and the resulting stable hydrazones were detected by immunoanalysis of proteins separated by one- or two-dimensional gel electrophoresis. The overall level of protein carbonylation increased strongly in cells treated with hydrogen peroxide. Several proteins, including the elongation factors EF-G, TufA and EF-Ts, were found to be highly carbonylated. Induction of the peroxide specific stress response by treatment with sub-lethal peroxide concentrations, prior to exposure to otherwise lethal levels of peroxide, markedly reduced the degree of protein carbonylation. Cells starved for glucose also showed only minor amounts of peroxide-mediated protein carbonylation compared to exponentially growing cells. We could not detect any differences between wild-type and deltasigB cells starved for glucose or preadapted by heat treatment with respect to the amount or specificity of protein damage incurred upon subsequent exposure to peroxide stress. However, artificial preloading with proteins that are normally induced by sigmaB-dependent mechanisms resulted in a lower level of protein carbonylation when cells were later subjected to oxidative stress.

Bacillus subtilis↗

PubMed2003

Intercellular signalling within vascular cells under high D-glucose involves free radical-triggered tyrosine kinase activation.

AIMS/HYPOTHESIS: Diabetes mellitus is associated with endothelial dysfunction in human arteries due to the release of superoxide anions (*O(2)(-)) that was found to occur predominantly in smooth muscle cells (SMC). This study was designed to elucidate the impact of high glucose concentration mediated radical production in SMC on EC. Pre-treatment of vascular SMC with increased D-glucose enhanced release of *O(2)(-). METHODS: Microscope-based analyses of intracellular free Ca(2+) concentration (fura-2), immunohistochemistry (f-actin) and tyrosine kinase activity were performed. Furthermore, RT-PCR and Western blots were carried out. RESULTS: Interaction of EC with SMC pre-exposed to high glucose concentration yielded changes in endothelial Ca(2+) signalling and polymerization of f-actin in a concentration-dependent and superoxide dismutase (SOD) sensitive manner. This interaction activated endothelial tyrosine kinase(s) but not NFkappaB and AP-1, while SOD prevented tyrosine kinase stimulation but facilitated NFkappaB and AP-1 activation. Erbstatin, herbimycin A and the src family specific kinase inhibitor PP-1 but not the protein kinase C inhibitor GF109203X prevented changes in endothelial Ca(2+) signalling and cytoskeleton organization induced by pre-exposure of SMC to high glucose concentration. Adenovirus-mediated expression of kinase-inactive c-src blunted the effect of pre-exposure of SMC to high glucose concentration on EC. CONCLUSIONS/INTERPRETATION: These data suggest that SMC-derived *O(2)(-) alter endothelial cytoskeleton organization and Ca(2+) signalling via activation of c-src. The activation of c-src by SMC-derived radicals is a new concept of the mechanisms underlying vascular dysfunction in diabetes.

Animals↗

PubMed2003

Essential Bacillus subtilis genes.

To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximately 4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from bacteria with small genomes. Unexpectedly, most genes involved in the Embden-Meyerhof-Parnas pathway are essential. Identification of unknown and unexpected essential genes opens research avenues to better understanding of processes that sustain bacterial life.

Bacillus subtilis↗

PubMed2003

Novel genetic variation of human interleukin-21 receptor is associated with elevated IgE levels in females.

The interleukin-21 receptor (IL21R) was recently discovered as a novel member of the class-I-cytokine-receptor family and is selectively expressed in lymphoid tissues. IL21R shows strong sequence homologies to the interleukin-4 receptor alpha chain gene (IL4RA). In addition, both genes are adjacent and share structural similarity. We analyzed all the exons of the human IL21R gene and its 5' flanking region for sequence variation. We identified four novel single nucleotide polymorphisms (SNPs) and genotyped 300 healthy blood donors. Total serum IgE levels were measured in all subjects and associated with IL21R SNPs. Results revealed a significant association of one IL21R polymorphism (T-83C) with elevated IgE levels (>100 kU/I) in females (OR=3.000, CI=[1.163;8.385], P=0.015, n=138). This was confirmed in a second prospectively collected group of female blood donors (OR=2.535, CI=[0.927;6.733], P=0.046, n=123). In contrast, no effects were observed in male subjects in either population. These findings identify IL21R as a possible novel target locus influencing IgE synthesis in female individuals.

Female↗